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Showing 1 - 200 of 339 Journals sorted alphabetically
Abstract and Applied Analysis     Open Access   (Followers: 3, SJR: 0.343, CiteScore: 1)
Active and Passive Electronic Components     Open Access   (Followers: 7, SJR: 0.136, CiteScore: 0)
Advances in Acoustics and Vibration     Open Access   (Followers: 36, SJR: 0.147, CiteScore: 0)
Advances in Aerospace Engineering     Open Access   (Followers: 54)
Advances in Agriculture     Open Access   (Followers: 9)
Advances in Artificial Intelligence     Open Access   (Followers: 15)
Advances in Astronomy     Open Access   (Followers: 39, SJR: 0.257, CiteScore: 1)
Advances in Bioinformatics     Open Access   (Followers: 17, SJR: 0.565, CiteScore: 2)
Advances in Biology     Open Access   (Followers: 9)
Advances in Chemistry     Open Access   (Followers: 25)
Advances in Civil Engineering     Open Access   (Followers: 43, SJR: 0.539, CiteScore: 1)
Advances in Computer Engineering     Open Access   (Followers: 4)
Advances in Condensed Matter Physics     Open Access   (Followers: 11, SJR: 0.315, CiteScore: 1)
Advances in Decision Sciences     Open Access   (Followers: 3, SJR: 0.303, CiteScore: 1)
Advances in Electrical Engineering     Open Access   (Followers: 34)
Advances in Electronics     Open Access   (Followers: 76)
Advances in Emergency Medicine     Open Access   (Followers: 12)
Advances in Endocrinology     Open Access   (Followers: 6)
Advances in Environmental Chemistry     Open Access   (Followers: 7)
Advances in Epidemiology     Open Access   (Followers: 8)
Advances in Fuzzy Systems     Open Access   (Followers: 5, SJR: 0.161, CiteScore: 1)
Advances in Geology     Open Access   (Followers: 19)
Advances in Geriatrics     Open Access   (Followers: 5)
Advances in Hematology     Open Access   (Followers: 11, SJR: 0.661, CiteScore: 2)
Advances in Hepatology     Open Access   (Followers: 2)
Advances in High Energy Physics     Open Access   (Followers: 19, SJR: 0.866, CiteScore: 2)
Advances in Human-Computer Interaction     Open Access   (Followers: 21, SJR: 0.186, CiteScore: 1)
Advances in Materials Science and Engineering     Open Access   (Followers: 30, SJR: 0.315, CiteScore: 1)
Advances in Mathematical Physics     Open Access   (Followers: 5, SJR: 0.218, CiteScore: 1)
Advances in Medicine     Open Access   (Followers: 3)
Advances in Meteorology     Open Access   (Followers: 24, SJR: 0.48, CiteScore: 1)
Advances in Multimedia     Open Access   (Followers: 2, SJR: 0.173, CiteScore: 1)
Advances in Nonlinear Optics     Open Access   (Followers: 6)
Advances in Numerical Analysis     Open Access   (Followers: 7)
Advances in Nursing     Open Access   (Followers: 32)
Advances in Operations Research     Open Access   (Followers: 12, SJR: 0.205, CiteScore: 1)
Advances in Optical Technologies     Open Access   (Followers: 4, SJR: 0.214, CiteScore: 1)
Advances in Optics     Open Access   (Followers: 5)
Advances in OptoElectronics     Open Access   (Followers: 6, SJR: 0.141, CiteScore: 0)
Advances in Orthopedics     Open Access   (Followers: 8, SJR: 0.922, CiteScore: 2)
Advances in Pharmacological Sciences     Open Access   (Followers: 8, SJR: 0.591, CiteScore: 2)
Advances in Physical Chemistry     Open Access   (Followers: 10, SJR: 0.179, CiteScore: 1)
Advances in Power Electronics     Open Access   (Followers: 33, SJR: 0.184, CiteScore: 0)
Advances in Preventive Medicine     Open Access   (Followers: 6)
Advances in Public Health     Open Access   (Followers: 25)
Advances in Regenerative Medicine     Open Access   (Followers: 3)
Advances in Software Engineering     Open Access   (Followers: 10)
Advances in Statistics     Open Access   (Followers: 4)
Advances in Toxicology     Open Access   (Followers: 2)
Advances in Tribology     Open Access   (Followers: 14, SJR: 0.265, CiteScore: 1)
Advances in Urology     Open Access   (Followers: 9, SJR: 0.51, CiteScore: 1)
Advances in Virology     Open Access   (Followers: 7, SJR: 0.838, CiteScore: 2)
AIDS Research and Treatment     Open Access   (Followers: 3, SJR: 0.758, CiteScore: 2)
Analytical Cellular Pathology     Open Access   (Followers: 2, SJR: 0.886, CiteScore: 2)
Anatomy Research Intl.     Open Access   (Followers: 2)
Anemia     Open Access   (Followers: 5, SJR: 0.669, CiteScore: 2)
Anesthesiology Research and Practice     Open Access   (Followers: 14, SJR: 0.501, CiteScore: 1)
Applied and Environmental Soil Science     Open Access   (Followers: 17, SJR: 0.451, CiteScore: 1)
Applied Bionics and Biomechanics     Open Access   (Followers: 7, SJR: 0.288, CiteScore: 1)
Applied Computational Intelligence and Soft Computing     Open Access   (Followers: 14)
Archaea     Open Access   (Followers: 3, SJR: 0.852, CiteScore: 2)
Arthritis     Open Access   (Followers: 6, SJR: 0.454, CiteScore: 1)
Autism Research and Treatment     Open Access   (Followers: 27)
Autoimmune Diseases     Open Access   (Followers: 3, SJR: 0.805, CiteScore: 2)
Behavioural Neurology     Open Access   (Followers: 10, SJR: 0.786, CiteScore: 2)
Biochemistry Research Intl.     Open Access   (Followers: 6, SJR: 0.437, CiteScore: 2)
Bioinorganic Chemistry and Applications     Open Access   (Followers: 11, SJR: 0.419, CiteScore: 2)
BioMed Research Intl.     Open Access   (Followers: 4, SJR: 0.935, CiteScore: 3)
Biotechnology Research Intl.     Open Access   (Followers: 1)
Bone Marrow Research     Open Access   (Followers: 2, SJR: 0.531, CiteScore: 1)
Canadian J. of Gastroenterology & Hepatology     Open Access   (Followers: 6, SJR: 0.867, CiteScore: 1)
Canadian J. of Infectious Diseases and Medical Microbiology     Open Access   (Followers: 6, SJR: 0.548, CiteScore: 1)
Canadian Respiratory J.     Open Access   (Followers: 1, SJR: 0.474, CiteScore: 1)
Cardiology Research and Practice     Open Access   (Followers: 8, SJR: 1.237, CiteScore: 4)
Case Reports in Anesthesiology     Open Access   (Followers: 10)
Case Reports in Cardiology     Open Access   (Followers: 4, SJR: 0.219, CiteScore: 0)
Case Reports in Critical Care     Open Access   (Followers: 10)
Case Reports in Dentistry     Open Access   (Followers: 5, SJR: 0.229, CiteScore: 0)
Case Reports in Dermatological Medicine     Open Access   (Followers: 2)
Case Reports in Emergency Medicine     Open Access   (Followers: 14)
Case Reports in Endocrinology     Open Access   (Followers: 1, SJR: 0.209, CiteScore: 1)
Case Reports in Gastrointestinal Medicine     Open Access   (Followers: 3)
Case Reports in Genetics     Open Access   (Followers: 1)
Case Reports in Hematology     Open Access   (Followers: 4)
Case Reports in Hepatology     Open Access   (Followers: 2)
Case Reports in Immunology     Open Access   (Followers: 4)
Case Reports in Infectious Diseases     Open Access   (Followers: 5)
Case Reports in Medicine     Open Access   (Followers: 2)
Case Reports in Nephrology     Open Access   (Followers: 4)
Case Reports in Neurological Medicine     Open Access   (Followers: 1)
Case Reports in Obstetrics and Gynecology     Open Access   (Followers: 10)
Case Reports in Oncological Medicine     Open Access   (Followers: 2, SJR: 0.204, CiteScore: 1)
Case Reports in Ophthalmological Medicine     Open Access   (Followers: 3)
Case Reports in Orthopedics     Open Access   (Followers: 5)
Case Reports in Otolaryngology     Open Access   (Followers: 6)
Case Reports in Pathology     Open Access   (Followers: 5)
Case Reports in Pediatrics     Open Access   (Followers: 7)
Case Reports in Psychiatry     Open Access   (Followers: 14)
Case Reports in Pulmonology     Open Access   (Followers: 3)
Case Reports in Radiology     Open Access   (Followers: 9)
Case Reports in Rheumatology     Open Access   (Followers: 6)
Case Reports in Surgery     Open Access   (Followers: 11)
Case Reports in Transplantation     Open Access  
Case Reports in Urology     Open Access   (Followers: 9)
Case Reports in Vascular Medicine     Open Access  
Case Reports in Veterinary Medicine     Open Access   (Followers: 5)
Child Development Research     Open Access   (Followers: 18, SJR: 0.144, CiteScore: 0)
Chinese J. of Engineering     Open Access   (Followers: 2, SJR: 0.114, CiteScore: 0)
Chinese J. of Mathematics     Open Access  
Cholesterol     Open Access   (Followers: 1, SJR: 0.424, CiteScore: 1)
Chromatography Research Intl.     Open Access   (Followers: 5)
Complexity     Hybrid Journal   (Followers: 6, SJR: 0.531, CiteScore: 2)
Computational and Mathematical Methods in Medicine     Open Access   (Followers: 2, SJR: 0.403, CiteScore: 1)
Computational Intelligence and Neuroscience     Open Access   (Followers: 12, SJR: 0.326, CiteScore: 1)
Contrast Media & Molecular Imaging     Open Access   (Followers: 3, SJR: 0.842, CiteScore: 3)
Critical Care Research and Practice     Open Access   (Followers: 12, SJR: 0.499, CiteScore: 1)
Current Gerontology and Geriatrics Research     Open Access   (Followers: 9, SJR: 0.512, CiteScore: 2)
Depression Research and Treatment     Open Access   (Followers: 15, SJR: 0.816, CiteScore: 2)
Dermatology Research and Practice     Open Access   (Followers: 3, SJR: 0.806, CiteScore: 2)
Diagnostic and Therapeutic Endoscopy     Open Access   (Followers: 1, SJR: 0.201, CiteScore: 1)
Discrete Dynamics in Nature and Society     Open Access   (Followers: 5, SJR: 0.279, CiteScore: 1)
Disease Markers     Open Access   (Followers: 1, SJR: 0.9, CiteScore: 2)
Economics Research Intl.     Open Access   (Followers: 1)
Education Research Intl.     Open Access   (Followers: 19)
Emergency Medicine Intl.     Open Access   (Followers: 9, SJR: 0.298, CiteScore: 1)
Enzyme Research     Open Access   (Followers: 4, SJR: 0.653, CiteScore: 3)
Evidence-based Complementary and Alternative Medicine     Open Access   (Followers: 22, SJR: 0.683, CiteScore: 2)
Game Theory     Open Access   (Followers: 1)
Gastroenterology Research and Practice     Open Access   (Followers: 3, SJR: 0.768, CiteScore: 2)
Genetics Research Intl.     Open Access   (Followers: 1, SJR: 0.61, CiteScore: 2)
Geofluids     Open Access   (Followers: 4, SJR: 0.952, CiteScore: 2)
Hepatitis Research and Treatment     Open Access   (Followers: 6, SJR: 0.389, CiteScore: 2)
HPB Surgery     Open Access   (Followers: 6, SJR: 0.824, CiteScore: 2)
Infectious Diseases in Obstetrics and Gynecology     Open Access   (Followers: 5, SJR: 1.27, CiteScore: 2)
Interdisciplinary Perspectives on Infectious Diseases     Open Access   (Followers: 1, SJR: 0.627, CiteScore: 2)
Intl. J. of Aerospace Engineering     Open Access   (Followers: 74, SJR: 0.232, CiteScore: 1)
Intl. J. of Agronomy     Open Access   (Followers: 6, SJR: 0.311, CiteScore: 1)
Intl. J. of Alzheimer's Disease     Open Access   (Followers: 11, SJR: 0.787, CiteScore: 3)
Intl. J. of Analysis     Open Access  
Intl. J. of Analytical Chemistry     Open Access   (Followers: 22, SJR: 0.285, CiteScore: 1)
Intl. J. of Antennas and Propagation     Open Access   (Followers: 11, SJR: 0.233, CiteScore: 1)
Intl. J. of Atmospheric Sciences     Open Access   (Followers: 21)
Intl. J. of Biodiversity     Open Access   (Followers: 4)
Intl. J. of Biomaterials     Open Access   (Followers: 4, SJR: 0.511, CiteScore: 2)
Intl. J. of Biomedical Imaging     Open Access   (Followers: 3, SJR: 0.501, CiteScore: 2)
Intl. J. of Breast Cancer     Open Access   (Followers: 13, SJR: 1.025, CiteScore: 2)
Intl. J. of Cell Biology     Open Access   (Followers: 4, SJR: 1.887, CiteScore: 4)
Intl. J. of Chemical Engineering     Open Access   (Followers: 8, SJR: 0.327, CiteScore: 1)
Intl. J. of Chronic Diseases     Open Access   (Followers: 1)
Intl. J. of Combinatorics     Open Access   (Followers: 1)
Intl. J. of Computer Games Technology     Open Access   (Followers: 10, SJR: 0.287, CiteScore: 2)
Intl. J. of Corrosion     Open Access   (Followers: 10, SJR: 0.194, CiteScore: 1)
Intl. J. of Dentistry     Open Access   (Followers: 6, SJR: 0.649, CiteScore: 2)
Intl. J. of Differential Equations     Open Access   (Followers: 8, SJR: 0.191, CiteScore: 0)
Intl. J. of Digital Multimedia Broadcasting     Open Access   (Followers: 5, SJR: 0.296, CiteScore: 2)
Intl. J. of Electrochemistry     Open Access   (Followers: 8)
Intl. J. of Endocrinology     Open Access   (Followers: 4, SJR: 1.012, CiteScore: 3)
Intl. J. of Engineering Mathematics     Open Access   (Followers: 5)
Intl. J. of Food Science     Open Access   (Followers: 4, SJR: 0.44, CiteScore: 2)
Intl. J. of Forestry Research     Open Access   (Followers: 3, SJR: 0.373, CiteScore: 1)
Intl. J. of Genomics     Open Access   (Followers: 2, SJR: 0.868, CiteScore: 3)
Intl. J. of Geophysics     Open Access   (Followers: 5, SJR: 0.182, CiteScore: 1)
Intl. J. of Hepatology     Open Access   (Followers: 5, SJR: 0.874, CiteScore: 2)
Intl. J. of Hypertension     Open Access   (Followers: 6, SJR: 0.578, CiteScore: 1)
Intl. J. of Inflammation     Open Access   (SJR: 1.264, CiteScore: 3)
Intl. J. of Inorganic Chemistry     Open Access   (Followers: 3)
Intl. J. of Manufacturing Engineering     Open Access   (Followers: 2)
Intl. J. of Mathematics and Mathematical Sciences     Open Access   (Followers: 3, SJR: 0.177, CiteScore: 0)
Intl. J. of Medicinal Chemistry     Open Access   (Followers: 6, SJR: 0.31, CiteScore: 1)
Intl. J. of Metals     Open Access   (Followers: 5)
Intl. J. of Microbiology     Open Access   (Followers: 5, SJR: 0.662, CiteScore: 2)
Intl. J. of Microwave Science and Technology     Open Access   (Followers: 3, SJR: 0.136, CiteScore: 1)
Intl. J. of Navigation and Observation     Open Access   (Followers: 20, SJR: 0.267, CiteScore: 2)
Intl. J. of Nephrology     Open Access   (Followers: 1, SJR: 0.697, CiteScore: 1)
Intl. J. of Oceanography     Open Access   (Followers: 7)
Intl. J. of Optics     Open Access   (Followers: 7, SJR: 0.231, CiteScore: 1)
Intl. J. of Otolaryngology     Open Access   (Followers: 3)
Intl. J. of Partial Differential Equations     Open Access   (Followers: 2)
Intl. J. of Pediatrics     Open Access   (Followers: 6)
Intl. J. of Peptides     Open Access   (Followers: 4, SJR: 0.46, CiteScore: 1)
Intl. J. of Photoenergy     Open Access   (Followers: 2, SJR: 0.341, CiteScore: 1)
Intl. J. of Plant Genomics     Open Access   (Followers: 4, SJR: 0.583, CiteScore: 1)
Intl. J. of Polymer Science     Open Access   (Followers: 24, SJR: 0.298, CiteScore: 1)
Intl. J. of Population Research     Open Access   (Followers: 3)
Intl. J. of Quality, Statistics, and Reliability     Open Access   (Followers: 16)
Intl. J. of Reconfigurable Computing     Open Access   (SJR: 0.123, CiteScore: 1)
Intl. J. of Reproductive Medicine     Open Access   (Followers: 4)
Intl. J. of Rheumatology     Open Access   (Followers: 4, SJR: 0.645, CiteScore: 2)
Intl. J. of Rotating Machinery     Open Access   (Followers: 2, SJR: 0.193, CiteScore: 1)
Intl. J. of Spectroscopy     Open Access   (Followers: 8)
Intl. J. of Stochastic Analysis     Open Access   (Followers: 3, SJR: 0.279, CiteScore: 1)
Intl. J. of Surgical Oncology     Open Access   (Followers: 1, SJR: 0.573, CiteScore: 2)
Intl. J. of Telemedicine and Applications     Open Access   (Followers: 5, SJR: 0.403, CiteScore: 2)
Intl. J. of Vascular Medicine     Open Access   (SJR: 0.782, CiteScore: 2)
Intl. J. of Zoology     Open Access   (Followers: 2, SJR: 0.209, CiteScore: 1)
Intl. Scholarly Research Notices     Open Access   (Followers: 199)
ISRN Astronomy and Astrophysics     Open Access   (Followers: 7)
J. of Addiction     Open Access   (Followers: 14)
J. of Advanced Transportation     Hybrid Journal   (Followers: 13, SJR: 0.581, CiteScore: 1)
J. of Aerodynamics     Open Access   (Followers: 12)

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Journal Cover
Journal of Diabetes Research
Number of Followers: 14  

  This is an Open Access Journal Open Access journal
ISSN (Print) 1687-5214 - ISSN (Online) 1687-5303
Published by Hindawi Homepage  [339 journals]
  • Association of Higher Circulating Insulin Antibody with Increased Mean
           Amplitude Glycemic Excursion in Patients with Type 2 Diabetes Mellitus: A
           Cross-Sectional, Retrospective Case-Control Study

    • Abstract: Insulin antibody (IA) may potentially affect a patient’s glycemic control due to its variability in both binding and/or releasing insulin. However, the association between IA titer and daily glycemic variability (GV) is still unknown. We thus performed this cross-sectional, retrospective case-control study to assess the relationship between IA titer and mean amplitude glycemic excursion (MAGE) in type 2 diabetes mellitus (T2DM) patients using a continuous glucose monitoring (CGM) system. We recruited 100 eligible patients (, IA positive) and divided them into two groups—a low (L) group and a high (H) group—based on their IA titer. The control (C) group consisted of 47 patients (, IA negative) matched for age, BMI, gender, and glycosylated hemoglobin A1c (HbA1c). The CGM determined the GV of enrolled patients. The primary outcome was the relationship between the IA titer and the MAGE, and the secondary outcome was the differences of GV among the three groups. We found that patients in the H group had higher levels of blood glucose fluctuation parameters than those in the L and C groups. The Ln(IA) was positively correlated with Ln(MAGE) even after adjusting for age, gender, BMI, HbA1c, and fasting and postprandial C-peptide(,). Multiple linear stepwise regression analysis revealed that Ln(IA) was an independent factor of Ln(MAGE) (,). In conclusion, the higher circulating IA titer was associated with increased MAGE in T2DM patients, indicating that those patients with elevated IA titer should receive GV assessment and individualized treatment.
      PubDate: Mon, 18 Mar 2019 13:05:16 +000
  • Cystatin C Is an Important Biomarker for Cardiovascular Autonomic
           Dysfunction in Chinese Type 2 Diabetic Patients

    • Abstract: Background. Cardiovascular autonomic dysfunction is closely related to increased mortality in patients with diabetes. Previous studies have proved that cystatin C (CysC) is an important predictor of both peripheral neuropathy and cardiovascular events. However, whether CysC is also associated with cardiovascular autonomic dysfunction remains unclear. Therefore, the aim of this study was to investigate the relationship between CysC and cardiovascular autonomic dysfunction in type 2 diabetic patients without renal dysfunction. Methods. A total of 161 type 2 diabetic patients with normal serum creatinine (less than 133 μmol/l) and estimated glomerular filtration rate (eGFR) higher than 60 ml/min per 1.73 m2 were recruited in our study. Cardiovascular autonomic dysfunction was determined by heart rate variability (HRV) measured by a 24-hour Holter monitor. Serum CysC was tested by particle-enhanced turbidimetric immunoassay, and subjects were divided into three groups based on the tertiles of CysC. Pearson correlation analysis was used to evaluate the association between different indexes, and the association of CysC with HRV indexes was assessed by multivariate linear regression analysis. Results. The HRV parameters were lower in the group with the highest CysC concentration than in the groups with lower levels of CysC (). Pearson correlation analysis showed a negative relationship between CysC and the HRV parameters, including SDNN (,), SDANN (,), and logLF (,). Furthermore, multivariate linear regression analysis revealed that CysC was independently correlated with SDNN (,) and SDANN (,) after adjusting for the confounding factors of gender, age, blood pressure, body mass index, eGFR, and hemoglobin A1c. Conclusions. Serum CysC levels are associated with cardiovascular autonomic dysfunction; furthermore, CysC may be a reliable and convenient biomarker for detecting cardiovascular autonomic dysfunction.
      PubDate: Mon, 18 Mar 2019 10:05:22 +000
  • Adaptive Optics (rtx1) High-Resolution Imaging of Photoreceptors and
           Retinal Arteries in Patients with Diabetic Retinopathy

    • Abstract: Background. Diabetic retinopathy (DR) is the leading cause of impaired vision in patients with diabetes mellitus. An adaptive optics retinal camera (rtx1™; Imagine Eyes, France) was used to capture images of cones and retinal arteries from patients with DR. Objective. Cone parameters (density, interphotoreceptor distance, and regularity) and retinal artery parameters (wall thickness, lumen diameter, WLR, and WCSA) were analyzed in 36 patients with nonproliferative DR (NPDR; 22 with mild NPDR and 14 with moderate NPDR) and in 20 healthy volunteers (the control group). Results. Cone density at 2° eccentricities was significantly lower in the DR compared to the control group (/mm2 vs. cells/mm2, respectively). Cone density and regularity decreased with increasing severity of DR. The artery walls were significantly thicker in the DR group. The WLR and WCSA differed significantly between the DR and the control groups (WLR vs. ; WCSA vs. , respectively). Conclusions. Decreased cone regularity and density are seen in patients with mild and moderate NPDR. Abnormalities of retinal arterioles show signs of arteriolar dysfunction in DR. Retinal image analysis with the rtx1 offers a novel noninvasive measurement of early changes in the neural cells and retina vasculature in diabetic eyes.
      PubDate: Sun, 17 Mar 2019 13:05:06 +000
  • Unlike PD-L1, PD-1 Is Downregulated on Partial Immune Cells in Type 2

    • Abstract: Introduction. Type 2 diabetes is a worldwide disease which is associated with chronic, low-grade inflammation. The PD-1/PD-L1 pathway has been reported to be a negative regulatory element in immune homeostasis and to be involved in many diseases. Materials and Methods. Peripheral blood mononuclear cells (PBMCs) were obtained from type 2 diabetes patients () and healthy donors (). The PD-L1 and PD-1 expressions on corresponding immune cells were evaluated by flow cytometry. Results. The PD-L1 expression on corresponding immune cells has no significant difference between these two groups. We showed the downregulated PD-1 expression in type 2 diabetes patients. The correlation analysis indicated that the PD-1 on NK cells has a positive correlation with insulin and diabetes duration. And an inverse correlation has been shown between the PD-1 expression on monocytes and BMI (body mass index). Conclusions. The results in this article suggest that PD-1, unlike PD-L1, might participate in the progression of type 2 diabetes. This investigation will provide evidence for the potential immune therapy for T2D.
      PubDate: Sun, 17 Mar 2019 12:05:13 +000
  • A New Way for Beta Cell Neogenesis: Transdifferentiation from Alpha Cells
           Induced by Glucagon-Like Peptide 1

    • Abstract: Recent studies showed that alpha cells, especially immature cells and proalpha cells, might be the precursors of beta cells. Exposure to glucagon-like peptide 1 (GLP1) can ameliorate hyperglycemia in diabetic mice and restore the beta cell mass. In the present study, we adopted single high-dose (60 mg/kg, i.p.) streptozotocin (STZ) to model diabetes mellitus (DM) and randomly assigned short-tail (SD) rats to a normal group, a diabetic group, GLP1 groups (50 μg/kg, 100 μg/kg, and 200 μg/kg), a GLP1 (200 μg/kg) with exendin (9-39) group, and a GLP1 with LY294002 group. We found that the pancreatic insulin-glucagon-positive cell populations increased according to the increase in GLP1 exposure. By contrast, no insulin-amylase-positive cell populations or insulin/pan-cytokeratin cells were observed in the pancreatic sections. The GLP1 receptor antagonist exendin (9-39) and the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) family inhibitor LY294002 not only suppressed protein kinase B (Akt), pancreatic and duodenal homeobox 1 (Pdx1), forkhead box O 1 (FoxO1), and mast cell function-associated antigen A (MafA) mRNA expression but also increased MAFB expression. We concluded that treatment with GLP1 might result in beta cell neogenesis by promoting the transdifferentiation of alpha cells but not by pancreatic acinar cells, ductal cells, or the self-replication of beta cells. The regulation on the GLP1 receptor and its downstream transcription factor PI3K/AKT/FOXO1 pathway, which causes increased pancreatic and duodenal homeobox 1 (Pdx1) and MafA mRNA expression but causes decreased MAFB expression, may be the mechanism involved in this process.
      PubDate: Wed, 13 Mar 2019 13:05:08 +000
  • Exosome-Like Vesicles as New Mediators and Therapeutic Targets for
           Treating Insulin Resistance and β-Cell Mass Failure in Type 2 Diabetes

    • Abstract: Exosome-like vesicles (ELVs), the smallest class of extracellular vesicles released from cells, function in cellular crosstalk and therefore profoundly affect physiologic responses and pathologic progression. A growing body of evidence supports a novel role for ELVs as important mediators and therapeutic targets due to their effects on regulation of both insulin signaling and β-cell mass. Pathologic conditions associated with type 2 diabetes (such as high blood glucose, inflammation, hypoxia, and fatty acids) can alter the quantity and components of ELVs secreted from the pancreas or peripheral insulin-targeting tissues. These released ELVs can either enter the blood circulation or be taken up by neighboring cells or macrophages, which can lead to insulin resistance or β-cell apoptosis. This review focuses on the roles of ELVs in insulin resistance and β-cell failure and also highlights the potential use of ELVs and exosome-based delivery systems in therapeutic interventions aimed at treating type 2 diabetes mellitus as well as the challenges associated with exosome-targeting therapeutics.
      PubDate: Tue, 12 Mar 2019 13:05:04 +000
  • Repetition of Prediabetes Enhances the Risk of Developing Diabetes

    • Abstract: We attempted to clarify the severity of the risk of diabetes mellitus (DM) in the individuals who repeatedly fulfill the criteria for prediabetes in both fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). The subjects were 2347 individuals who underwent annual health checkup at our hospital. They were classified as normal glucose tolerance or prediabetes as their yearly status of glucose tolerance for three years; furthermore, the individuals classified as prediabetes were subclassified into 3 groups. Among them, we focused the individuals who fulfilled the criteria for prediabetes in both FPG and HbA1c, and this group was named as PD3. Similarly, all subjects were categorized into 4 groups by the frequency of the status of PD3 during three years. Moreover, all subjects were categorized into 8 patterns when PD3 status was positive. Then, we surveyed the development of diabetes for 5 years, and the incidence rates (IRs) and the age- and sex-adjusted odds ratios (ORs) were obtained. A total of 188 subjects developed diabetes. The individuals in the group of PD3 showed the highest IR of DM (33.6%). The values of ORs were 11.5, 20.0, and 63.5 when the frequencies of PD3 were one, two, and three, respectively. In the group whose frequency of PD3 was two, the individuals who had repeated the status of PD3 twice then moved to the status other than PD3 showed smaller risk of DM than the others in the same group. In conclusion, individuals who fulfill the criteria for prediabetes in both FPG and HbA1c were at a high risk of developing DM, and the risk was enhanced by repeating this status. On the other hand, changing the status from PD3 to others might reduce the risk of DM.
      PubDate: Tue, 12 Mar 2019 08:05:22 +000
  • Oral LPS Dosing Induces Local Immunological Changes in the Pancreatic
           Lymph Nodes in Mice

    • Abstract: Lacking the initial contact between the immune system and microbial-associated molecular patterns (MAMPs), such as lipopolysaccharides (LPS), early in life, may be regarded as one of the causal factors of the increasing global increase in the incidence of autoimmune diseases, such as type 1 diabetes (T1D). Previously, a reduced incidence of T1D accompanied by dramatically increased abundances of both the mucin-metabolising bacterium Akkermansia muciniphila, and LPS-carrying Proteobacteria was observed, when vancomycin was given to pups of nonobese diabetic (NOD) mice. While the T1D incidence reducing effect of A. muciniphila has been shown in further studies, little is known as to whether the increased abundance of LPS-carrying bacteria also has a protective effect. Therefore, we fed NOD pups with Eschericia coli LPS orally from birth to weaning, which decreased the gene expressions of TNFα, IL-10, IL-6, IFNγ, IL-1β, IL-2, IL-4, and FoxP3 in the pancreatic lymph nodes, while the same gene expression profile in the spleen was unaffected. However, no significant difference in the incidence of T1D, gut microbiota composition, or ileum expression of the genetic markers of gut permeability, Claudin8, Occludin, Zonulin-1 (Tjp1), Claudin15, Muc1, and Muc2 were observed in relation to LPS ingestion. It is, therefore, concluded that early life oral E. coli LPS has an impact on the local immune response, which, however, did not influence T1D incidence in NOD mice later in life.
      PubDate: Wed, 06 Mar 2019 07:05:14 +000
  • Different Contributions of Dyslipidemia and Obesity to the Natural History
           of Type 2 Diabetes: 3-Year Cohort Study in China

    • Abstract: Aim. It is known that different stages of type 2 diabetes represent distinct pathophysiological changes, but how the spectrum of risk factors varies at different stages is not yet clarified. Hence, the aim of this study was to compare the effect of different metabolic variables on the natural history of type 2 diabetes. Methods. A total of 5,213 nondiabetic (normal glucose tolerance (NGT) and prediabetes) Chinese older than 40 years participated this prospective cohort study, and 4,577 completed the 3-year follow-up. Glycemic status was determined by standard oral glucose tolerance test both at enrollment and follow-up visit. Predictors for conversion in glycemic status were studied in a corresponding subcohort using the multiple logistic regression analysis. Results. The incidence of prediabetes and diabetes of the cohort was 93.6 and 42.2 per 1,000 person-years, respectively. After a 3-year follow-up, 33.1% of prediabetes patients regressed to NGT. The predictive weight of body mass index (BMI), serum triglyceride, total cholesterol, and systolic blood pressure in different paths of conversions among diabetes, prediabetes, and NGT differed. Specifically, BMI was the strongest predictor for regression from prediabetes to NGT, while triglyceride was most prominent for onset of diabetes. One SD increase in serum triglyceride was associated with a 1.29- (95% CI 1.10–1.52; ) or 1.12- (95% CI 1.01–1.27; ) fold higher risk of diabetes for individuals with NGT or prediabetes, respectively. Conclusion. Risk factors for different stages of diabetes differed, suggesting personalized preventive strategies for individuals with different basal glycemic statuses.
      PubDate: Mon, 04 Mar 2019 14:05:06 +000
  • Corrigendum to “The Impact of Type 2 Diabetes Mellitus on Long-Term
           Prognosis in Patients of Different Ages with Myocardial Infarction”

    • PubDate: Mon, 04 Mar 2019 07:05:14 +000
  • Prevalence, Risk Factors, and Fetomaternal Outcomes of Gestational
           Diabetes Mellitus in Kuwait: A Cross-Sectional Study

    • Abstract: Objective. Gestational diabetes mellitus (GDM) is a growing global public health problem that can have short- and long-term health consequences for the mother and the child. Despite its criticalness, many countries still do not have the epidemiological data which could guide them in responding to the problem. Due to the lack of knowledge on GDM and the fact that diabetes and obesity are high in Kuwait, this study sought to estimate the prevalence of GDM and determine its risk factors and outcomes. Methods. This cross-sectional study enrolled 947 mothers living in Kuwait, who had given birth within the previous four years. Participants were recruited from primary health care clinics and public hospitals. GDM status was self-reported by the mother. Associations between exposures and outcomes were evaluated using logistic regression, and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated. Results. Of the 868 mothers with no prior history of diabetes mellitus, 109 (12.6%, 95% CI: 10.4, 14.8) reported having been given a GDM diagnosis during their last pregnancy. The prevalence of GDM increased with maternal age and prepregnancy body mass index. GDM was positively associated with caesarean section delivery (, 95% CI: 1.17, 2.66) and fetal macrosomia (, 95% CI: 1.14, 4.89). Conclusion. GDM is prevalent in Kuwait and is associated with poor maternal, fetal, and neonatal outcomes. To date, GDM has received little attention, and there is a need for more research to identify and respond to individual and public health implications of GDM in Kuwait.
      PubDate: Sun, 03 Mar 2019 09:05:22 +000
  • Evidence in Practice of Tissue Healing with Latex Biomembrane: Integrative

    • Abstract: Wound healing is a perfectly coordinated cascade of cellular, molecular, and biochemical events which interact in tissue reconstitution. Chronic diseases such as pressure ulcers (PU) and diabetes mellitus (DM) are considered risk factors for wound healing. Patients with such diseases often have higher sepsis, infection, and complication rates, since they have revascularization inhibition and low growth factor expression. Thus, latex biomembrane (LBM), a biocompatible material, derived from the latex of the rubber tree (Hevea brasiliensis) appears to create tendencies as an angiogenic-inducing tissue healing agent and as biomaterial, resulting from its structural qualities and its low cost when compared to conventional treatments. Therefore, this work aims at summarizing the results, experiments, and scientific findings that certify or recommend the use of LBM as a new technique to be applied effectively in the treatment of wounds. An integrative review was held in the BIREME, LILACS, Burns, MEDLINE, PubMed, and SciELO databases, from 2000 to 2016, using the following descriptors: “healing,” “diabetes mellitus,” “wounds,” and “latex membrane.” As a result, 600 experiments (out of 612) presented satisfactory results; however, 33% of the cases received explicit recommendations, 11% required more studies on the subjects, and 1% was denied. On the other hand, half of the studies did not expressly endorse its use, despite presenting satisfactory results. The LBM was characterized as a good therapeutic alternative in cases of wounds, including chronic diseases, such as diabetes mellitus and PU, due to its relevant potential for wound healing stimulation, acceleration of cell tissue mending and revascularization, or the reestablishment of angiogenic functions (creation of new blood vessels). The LBM was also confirmed to be safe as a biocompatible material whose structural qualities (elasticity, adaptability, impermeability, and possibility of suture), devoid of toxicity, allowed interaction between tissues and presented no hypersensitivity inducer and no antimicrobial effect.
      PubDate: Sun, 03 Mar 2019 08:05:44 +000
  • Predictors of Effectiveness of Glucagon-Like Peptide-1 Receptor Agonist
           Therapy in Patients with Type 2 Diabetes and Obesity

    • Abstract: Rationale. It is well known that diabetes mellitus (DM) exacerbates the mechanisms underlying atherosclerosis. Currently, glucagon-like peptide-1 receptor agonists (aGLP-1) have one of the most prominent cardioprotective effects among the antidiabetic agents. However, the treatment with aGLP-1 is effective only in 50-70% of the cases. Taking into account the high cost of these medications, discovery of the predictors of optimal response to treatment is required. Purpose. To identify the predictors of the greater impact of aGLP-1 on HbA1c levels, weight reduction, and improvement in lipid profile. Methods. The study group consisted of 40 patients with type 2 DM (T2DM) and obesity who were treated with aGLP-1. The follow-up period was 24 weeks. Patients’ evaluation was conducted at baseline and after 24 weeks. In addition, it included the assessment of the hormones involved in glucose and lipid metabolism and appetite regulation. Results. Patients who have initially higher BMI (body mass index), glycemia, and triglycerides (TG) had better improvement in these parameters undergoing aGLP-1 treatment. In patients with a BMI , GLP-1 and fasting ghrelin levels were higher and ghrelin level in postnutritional status was lower. The HbA1c levels decreased more intensively in participants with higher GLP-1 levels. TG responders had lower baseline fasting glucose-dependent insulinotropic peptide (GIP) and postprandial ghrelin levels. Conclusion. The evaluation of the glycemic control, lipid profile, and GLP-1, GIP, and ghrelin levels are useable for estimating the expected efficacy of aGLP-1.
      PubDate: Sun, 03 Mar 2019 08:05:42 +000
  • A Clinically Applicable Positive Allosteric Modulator of GABA Receptors
           Promotes Human β-Cell Replication and Survival as well as GABA’s
           Ability to Inhibit Inflammatory T Cells

    • Abstract: A major goal of T1D research is to develop new approaches to increase β-cell mass and control autoreactive T cell responses. GABAA-receptors (GABAA-Rs) are promising drug targets in both those regards due to their abilities to promote β-cell replication and survival, as well as inhibit autoreactive T cell responses. We previously showed that positive allosteric modulators (PAMs) of GABAA-Rs could promote rat β-cell line INS-1 and human islet cell replication in vitro. Here, we assessed whether treatment with alprazolam, a widely prescribed GABAA-R PAM, could promote β-cell survival and replication in human islets after implantation into NOD/scid mice. We observed that alprazolam treatment significantly reduced human islet cell apoptosis following transplantation and increased β-cell replication in the xenografts. Evidently, the GABAA-R PAM works in conjunction with GABA secreted from β-cells to increase β-cell survival and replication. Treatment with both the PAM and GABA further enhanced human β-cell replication. Alprazolam also augmented the ability of suboptimal doses of GABA to inhibit antigen-specific T cell responses in vitro. Thus, combined GABAA-R agonist and PAM treatment may help control inflammatory immune responses using reduced drug dosages. Together, these findings suggest that GABAA-R PAMs represent a promising drug class for safely modulating islet cells toward beneficial outcomes to help prevent or reverse T1D and, together with a GABAA-R agonist, may have broader applications for ameliorating other disorders in which inflammation contributes to the disease process.
      PubDate: Tue, 26 Feb 2019 09:05:14 +000
  • The APOE3-Leiden Heterozygous Glucokinase Knockout Mouse as Novel
           Translational Disease Model for Type 2 Diabetes, Dyslipidemia, and
           Diabetic Atherosclerosis

    • Abstract: Background. There is a lack of predictive preclinical animal models combining atherosclerosis and type 2 diabetes. APOE3-Leiden (E3L) mice are a well-established model for diet-induced hyperlipidemia and atherosclerosis, and glucokinase+/− (GK+/−) mice are a translatable disease model for glucose control in type 2 diabetes. The respective mice respond similarly to lipid-lowering and antidiabetic drugs as humans. The objective of this study was to evaluate/characterize the APOE3-Leiden.glucokinase+/− (E3L.GK+/−) mouse as a novel disease model to study the metabolic syndrome and diabetic complications. Methods. Female E3L.GK+/−, E3L, and GK+/− mice were fed fat- and cholesterol-containing diets for 37 weeks, and plasma parameters were measured throughout. Development of diabetic macro- and microvascular complications was evaluated. Results. Cholesterol and triglyceride levels were significantly elevated in E3L and E3L.GK+/− mice compared to GK+/− mice, whereas fasting glucose was significantly increased in E3L.GK+/− and GK+/− mice compared to E3L. Atherosclerotic lesion size was increased 2.2-fold in E3L.GK+/− mice as compared to E3L (), which was predicted by glucose exposure (,). E3L and E3L.GK+/− mice developed NASH with severe inflammation and fibrosis which, however, was not altered by introduction of the defective GK phenotype, whereas mild kidney pathology with tubular vacuolization was present in all three phenotypes. Conclusions. We conclude that the E3L.GK+/− mouse is a promising novel diet-inducible disease model for investigation of the etiology and evaluation of drug treatment on diabetic atherosclerosis.
      PubDate: Thu, 21 Feb 2019 13:05:22 +000
  • Glucagon-Like Peptide-1 Receptor Agonist Protects Dorsal Root Ganglion
           Neurons against Oxidative Insult

    • Abstract: Objective. Diabetic polyneuropathy (DPN) is one of the most prevalent diabetic complications. We previously demonstrated that exendin-4 (Ex4), a glucagon-like peptide-1 receptor agonist (GLP-1RA), has beneficial effects in animal models of DPN. We hypothesized that GLP-1 signaling would protect neurons of the peripheral nervous system from oxidative insult in DPN. Here, the therapeutic potential of GLP-1RAs on DPN was investigated in depth using the cellular oxidative insult model applied to the dorsal root ganglion (DRG) neuronal cell line. Research Design and Methods. Immortalized DRG neuronal 50B11 cells were cultured with and without hydrogen peroxide in the presence or absence of Ex4 or GLP-1(7-37). Cytotoxicity and viability were determined using a lactate dehydrogenase assay and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt), respectively. Antioxidant enzyme activity was evaluated using a superoxide dismutase assay. Alteration of neuronal characteristics of 50B11 cells induced by GLP-1RAs was evaluated with immunocytochemistry utilizing antibodies for transient receptor potential vanilloid subfamily member 1, substance P, and calcitonin gene-related peptide. Cell proliferation and apoptosis were also examined by ethynyl deoxyuridine incorporation assay and APOPercentage dye, respectively. The neurite projection ratio induced by treatment with GLP-1RAs was counted. Intracellular activation of adenylate cyclase/cyclic adenosine monophosphate (cAMP) signaling was also quantified after treatment with GLP-1RAs. Results. Neither Ex4 nor GLP-1(7-37) demonstrated cytotoxicity in the cells. An MTS assay revealed that GLP-1RAs amended impaired cell viability induced by oxidative insult in 50B11 cells. GLP-1RAs activated superoxide dismutase. GLP-1RAs induced no alteration of the distribution pattern in neuronal markers. Ex4 rescued the cells from oxidative insult-induced apoptosis. GLP-1RAs suppressed proliferation and promoted neurite projections. No GLP-1RAs induced an accumulation of cAMP. Conclusions. Our findings indicate that GLP-1RAs have neuroprotective potential which is achieved by their direct actions on DRG neurons. Beneficial effects of GLP-1RAs on DPN could be related to these direct actions on DRG neurons.
      PubDate: Thu, 21 Feb 2019 13:05:20 +000
  • Impaired Glucose Metabolism in Young Offspring of Female Rats with

    • Abstract: Purpose. Because thyroid hormones from the maternal thyroid glands are known to influence the growth, development, and metabolic functioning of offspring, we used a rat model to preliminarily investigate the effects of maternal hypothyroidism on glucose metabolism, pancreas cell proliferation, and insulin production in young male offspring and the possible underlying mechanisms. Methods. Female rats were divided into a maternal hypothyroidism (MH) group, which received water containing 0.02% 6-propyl-2-thiouracil before and during pregnancy to induce hypothyroidism, and a control group which consumed tap water. Results. Our results showed that there were no differences of islets structure between the offspring from the two groups, but glucose metabolism was impaired with higher plasma glucose concentrations at 0 and 15 min in the OGTT in 8-week-old offspring of the MH group. From birth to 8 weeks, pancreatic TRβ1 and TRβ2 mRNA level declined significantly in MH offspring, accompanied by decreased Ki67 and insulin mRNA expression. Conclusions. Maternal hypothyroidism results in impaired pancreatic insulin synthesis and pancreatic cell proliferation in neonatal offspring and subsequent glucose intolerance in young offspring, which may be related to TRβ gene downregulation in the pancreas.
      PubDate: Thu, 21 Feb 2019 10:05:24 +000
  • A Case-Control Study on Risk Factors and Their Interactions with
           Prediabetes among the Elderly in Rural Communities of Yiyang City, Hunan

    • Abstract: Background. The prevalence of prediabetes has been increasing significantly in recent years. Individuals with prediabetes have an increased risk of developing diabetes and cardiovascular diseases. The objectives of this study were to identify risk factors for prediabetes and their interactions among the elderly in rural communities of Hunan Province and to provide a scientific basis for prediabetes prevention. Methods. A case-control study was conducted to explore risk factors for prediabetes among the elderly in rural areas. The general sociodemographic information, lifestyle behaviours, and physiological results of elderly individuals with prediabetes and controls were collected by a questionnaire and laboratory testing. Conditional logistic regression was performed to identify the risk factors for prediabetes among the elderly, and additive interactions were used to analyse the interactions between risk factors. Results. A total of 425 elderly subjects with prediabetes were included in the case group, and 425 elderly subjects with normal plasma glucose levels were included in the control group. The main risk factors for prediabetes among the elderly in rural communities of Hunan Province were a family history of diabetes (; 95% CI: 1.13, 5.46), physical inactivity (; 95% CI: 1.95, 5.49), a lack of health literacy on diabetes prevention and control (; 95% CI: 1.62, 6.55), hypertension (; 95% CI: 1.38, 2.93), overweight (; 95% CI: 1.67, 3.81), obesity (; 95% CI: 1.48, 6.40), and a high waist-to-hip ratio (WHR) (; 95% CI: 1.45, 3.51). Additive interactions for prediabetes were detected between a high WHR and physical inactivity, with a relative excess risk due to interaction (RERI) of 6.30 (95% CI: 0.42, 12.18), and between a high WHR and overweight or obesity, with an RERI of 2.92 (95% CI: 0.56, 5.29). Conclusion. The independent risk factors for prediabetes are a family history of diabetes, physical inactivity, a lack of health literacy on diabetes prevention and control, hypertension, overweight or obesity, and a high WHR. A high WHR has additive interactions with physical inactivity and overweight or obesity for the risk of prediabetes. These findings have significant implications for prediabetes prevention among the elderly in rural areas.
      PubDate: Mon, 18 Feb 2019 13:05:14 +000
  • A Liquid-Based Cytology System, without the Use of Cytocentrifugation, for
           Detection of Podocytes in Urine Samples of Patients with Diabetic

    • Abstract: Objective. Podocytes have highly differentiated functions and are extremely difficult to grow; thus, damage of podocytes is associated with glomerular dysfunction. Desquamated podocytes can be detected in urine of patients with severe renal impairment. Unlike the rapidly progressive glomerular damage in glomerulonephritis, only a few desquamated podocytes are usually detected in diabetic nephropathy (DN). It is not clear whether the low podocyte count in DN is due to limitation of the conventional method or true pathological feature. The aim of this study was to compare the conventional method with a newly modified method in detecting podocytes in morning urine samples of patients with DN. Materials and Methods. The study subjects were patients with type 2 diabetes. Urine samples from these patients were analyzed by the conventional method (Cytospin®) and the modified method (SurePath™). We determined the rate of detection of urinary podocytes and the number of detected cells. Results. The detection rate and podocyte count were significantly higher by the modified method than by the conventional method. The differences in the detection rates and numbers of podocytes were not significant between patients with normoalbuminuria and those with macroalbuminuria. However, they were significant in patients with microalbuminuria. The number of podocytes in the urine correlated significantly with the albumin-to-creatinine ratio, but not with the estimated glomerular filtration rate. Conclusions. The true number of urinary podocytes, as measured by the modified SurePath™-based method, in patients with DN is much higher than that estimated by the conventional method.
      PubDate: Sun, 17 Feb 2019 13:05:44 +000
  • Micro- and Macrovascular Complications in Diabetes Mellitus: Preclinical
           and Clinical Studies

    • PubDate: Sun, 17 Feb 2019 13:05:42 +000
  • The Level of Serum Albumin Is Associated with Renal Prognosis in Patients
           with Diabetic Nephropathy

    • Abstract: Objective. Although hypoalbuminemia is frequently found in most patients with diabetic nephropathy (DN), its relationship to the severity and progression of DN remains largely unknown. Our aim was to investigate the association between the serum albumin levels and clinicopathological features and renal outcomes in patients with type 2 diabetes mellitus (T2DM) and biopsy-proven DN. Materials and Methods. A total of 188 patients with T2DM and biopsy-proven DN followed up for at least one year were enrolled. The patients were divided into four groups based on the albumin levels: normal group: ≥35 g/L (); mild group: 30-35 g/L (); moderate group: 25-30 g/L (); and severe group:
      PubDate: Sun, 17 Feb 2019 13:05:41 +000
  • Von Hippel-Lindau (VHL) Protein Antagonist VH298 Improves Wound Healing in
           Streptozotocin-Induced Hyperglycaemic Rats by Activating Hypoxia-Inducible
           Factor- (HIF-) 1 Signalling

    • Abstract: Aims. The purpose of the present research is to investigate the effects of the VHL protein antagonist, VH298, on functional activities of fibroblasts and vascular endothelial cells and the effects on the wound healing process in a streptozotocin-induced hyperglycaemic rat model. Methods. HIF-1α and hydroxy-HIF-1α protein levels in VH298-treated rat fibroblasts (rFb) were measured by immunoblotting, rFb proliferation was detected by the CCK-8 assay, and mRNA levels of related genes were measured by quantitative RT-PCR. In vitro wound healing was simulated by the scratch test; angiogenesis was measured by the human umbilical vein endothelial cell (hUVEC) tube formation assay. VH298 or PBS was locally injected into wounds in rat models with streptozotocin- (STZ-) induced hyperglycaemia, the wound tissues were harvested, and haematoxylin-eosin (HE) and Masson trichrome staining and immunohistochemical processes were conducted. Results. HIF-1α and hydroxy-HIF-1α levels increased in VH298-treated rFb, in a time- and dose-dependent manner. Thirty micromolar VH298 could significantly increase cell proliferation, angiogenesis, and gene expression of type I collagen-α1 (Col1-α1), vascular endothelial growth factor A (VEGF-A), and insulin-like growth factor 1 (IGF-1). The VH298-treated wound had a better healing pattern, activation of HIF-1 signalling, and vascularization. Conclusions. Taken together, VH298 activated the HIF-1 signalling pathway by stabilizing both HIF-1α and hydroxy-HIF-1α. VH298 enhanced rFb functions, promoted hUVEC angiogenesis, and accelerated wound healing in the rat model mimicking diabetes mellitus.
      PubDate: Sun, 17 Feb 2019 12:05:17 +000
  • Lipopolysaccharide (LPS) Aggravates High Glucose- and
           Hypoxia/Reoxygenation-Induced Injury through Activating ROS-Dependent
           NLRP3 Inflammasome-Mediated Pyroptosis in H9C2 Cardiomyocytes

    • Abstract: Diabetes aggravates myocardial ischemia-reperfusion (I/R) injury because of the combination effects of changes in glucose and lipid energy metabolism, oxidative stress, and systemic inflammatory response. Studies have indicated that myocardial I/R may coincide and interact with sepsis and inflammation. However, the role of LPS in hypoxia/reoxygenation (H/R) injury in cardiomyocytes under high glucose conditions is still unclear. Our objective was to examine whether lipopolysaccharide (LPS) could aggravate high glucose- (HG-) and hypoxia/reoxygenation- (H/R-) induced injury by upregulating ROS production to activate NLRP3 inflammasome-mediated pyroptosis in H9C2 cardiomyocytes. H9C2 cardiomyocytes were exposed to HG (30 mM) condition with or without LPS, along with caspase-1 inhibitor (Ac-YVAD-CMK), inflammasome inhibitor (BAY11-7082), ROS scavenger N-acetylcysteine (NAC), or not for 24 h, then subjected to 4 h of hypoxia followed by 2 h of reoxygenation (H/R). The cell viability, lactate dehydrogenase (LDH) release, caspase-1 activity, and intracellular ROS production were detected by using assay kits. The incidence of pyroptosis was detected by calcein-AM/propidium iodide (PI) double staining kit. The concentrations of IL-1β and IL-18 in the supernatants were assessed by ELISA. The mRNA levels of NLRP3, ASC, and caspase-1 were detected by qRT-PCR. The protein levels of NF-κB p65, NLRP3, ASC, cleaved caspase-1 (p10), IL-1β, and IL-18 were detected by western blot. The results indicated that pretreatment LPS with 1 μg/ml not 0.1 μg/ml could efficiently aggravate HG and H/R injury by activating NLRP3 inflammasome to mediate pyroptosis in H9C2 cells, as evidenced by increased LDH release and decreased cell viability in the cells, and increased expression of NLRP3, ASC, cleaved caspase-1 (p10), IL-1β, and IL-18. Meanwhile, Ac-YVAD-CMK, BAY11-7082, or NAC attenuated HG- and H/R-induced H9C2 cell injury with LPS stimulated by reversing the activation of NLRP3 inflammasome-mediated pyroptosis. In conclusion, LPS could increase the sensitivity of H9C2 cells to HG and H/R and aggravated HG- and H/R-induced H9C2 cell injury by promoting ROS production to induce NLRP3 inflammasome-mediated pyroptosis.
      PubDate: Sun, 17 Feb 2019 10:05:09 +000
  • Inhibition of HDAC3 Ameliorates Cerebral Ischemia Reperfusion Injury in
           Diabetic Mice In Vivo and In Vitro

    • Abstract: Background. A substantial increase in histone deacetylase 3 (HDAC3) expression is implicated in the pathological process of diabetes and stroke. However, it is unclear whether HDAC3 plays an important role in diabetes complicated with stroke. We aimed to explore the role and the potential mechanisms of HDAC3 in cerebral ischemia/reperfusion (I/R) injury in diabetic state. Methods. Diabetic mice were subjected to 1 h ischemia, followed by 24 h reperfusion. PC12 cells were exposed to high glucose for 24 h, followed by 3 h of hypoxia and 6 h of reoxygenation (H/R). Diabetic mice received RGFP966 (the specific HDAC3 inhibitor) or vehicle 30 minutes before the middle cerebral artery occlusion (MCAO), and high glucose-incubated PC12 cells were pretreated with RGFP966 or vehicle 6 h before H/R. Results. HDAC3 inhibition reduced the cerebral infarct volume, ameliorated pathological changes, improved the cell viability and cytotoxicity, alleviated apoptosis, attenuated oxidative stress, and enhanced autophagy in cerebral I/R injury model in diabetic state in vivo and in vitro. Furthermore, we found that the expression of HDAC3 was remarkably amplified, and the Bmal1 expression was notably decreased in diabetic mice with cerebral I/R, whereas this phenomenon was obviously reversed by RGFP966 pretreatment. Conclusions. These results suggested that the HDAC3 was involved in the pathological process of the complex disease of diabetic stroke. Suppression of HDAC3 exerted protective effects against cerebral I/R injury in diabetic state in vivo and in vitro via the modulation of oxidative stress, apoptosis, and autophagy, which might be mediated by the upregulation of Bmal1.
      PubDate: Wed, 13 Feb 2019 07:05:06 +000
  • Roles of Identified Long Noncoding RNA in Diabetic Nephropathy

    • Abstract: Diabetes mellitus is the leading chronic disease in the world, and diabetic nephropathy (DN) as one of its complications could increase the mortality. The development of DN is associated to abnormal hemodynamic factors like cytokine networks and the intervention of metabolic risk factors like blood pressure, blood glucose, and blood lipid. However, the pathogenesis of DN is still poorly understood. Although glucose-lowering drugs and insulins have significant effects on blood glucose, the fluctuation of blood glucose or other risk factors could continuously damage the kidney. Recent studies reported that the progression of DN is closely related to the expression of long noncoding RNA (lncRNA), which is important for the early diagnosis and targeted intervention of DN. In this review, we briefly summarize the published studies on the functions and potential mechanism of reported lncRNA in the regulation of DN.
      PubDate: Tue, 12 Feb 2019 08:05:26 +000
  • Dipeptidyl Peptidase 4 Activity Is Related to Body Composition, Measures
           of Adiposity, and Insulin Resistance in Subjects with Excessive Adiposity
           and Different Degrees of Glucose Tolerance

    • Abstract: Background. The enzyme dipeptidyl peptidase 4 (DPP4) has been recently recognized as an adipo-myokine. However, studies that associate its constitutive activity with body composition, anthropometry, and insulin resistance (IR) are very scarce and included only healthy people. Methods. First, we investigated the relationships of constitutive DPP4 activity, body composition (assessed by bioelectrical impedance analysis), and measures of adiposity and IR in fifty-two subjects of both sexes, 18-50 years, and BMI ≥25.0 kg/m2 who comprised three groups according to glucose tolerance. Additionally, we evaluated associations among DPP4 activity and adipokines, gut peptides, and biochemical variables at fasting and 30 and 60 min after a standardized meal intake. Results. DPP4 activity was no different among the three groups. At fasting, pooled analysis showed it was positively correlated with measures of central adiposity, such as WC () and WHR (), and with all measures of IR, but inversely related to indexes of general adiposity, such as fat mass percentage () and BAI (). DPP4 activity was also associated with lean mass (,). After meal intake, DPP4 activity remained significantly associated with insulin, leptin, and resistin. In multiple regression analysis, BAI, WHR, percent lean mass, HOMA-IR, and leptin influenced DPP4 activity and explained approximately 26% of the variance on it. Conclusions. Constitutive DPP4 activity is positively associated with lean mass, central adiposity, and IR and negatively to general adiposity. Furthermore, it seems to be influenced by body composition and IR and could also be viewed as an adipo-myokine in subjects with excessive adiposity and different stages of glucose tolerance.
      PubDate: Mon, 11 Feb 2019 12:05:37 +000
  • Prevalence and Determinants of Diabetic Foot Ulcers and Lower Extremity
           Amputations in Three Selected Tertiary Hospitals in Ghana

    • Abstract: Background. The occurrence and complications of diabetes are increasing worldwide. This study examined the prevalence and determinants of diabetic foot ulcers and lower extremity amputations in three selected tertiary hospitals in Ghana. Methods. A cross-sectional multicenter study involving 100 subjects was carried out. Subjects were selected through simple random sampling from three selected tertiary hospitals in Ghana. A structured questionnaire was used to document information on sociodemographic, medical history, lifestyle, and physical characteristics of subjects. Foot ulcers and lower extremity amputations were also investigated. Total cholesterol, triglycerides, low-density lipoproteins, high-density lipoproteins, serum urea, serum creatinine, and estimated glomerular filtration rate of subjects were assessed. Data analysis was done using SPSS version 22. Results. The study revealed that 31% and 69% were males and females, respectively, with a mean age of years. Among the patients, 11% had diabetic foot ulcers whilst 3% had lower extremity amputations. In the multivariate binary logistic regression analysis, previous history of foot ulcers (, 95% -299.9) and foot deformities (, 95% -161.2) were identified as independent predictors of diabetic foot ulcers. Foot deformity () and serum urea () were associated with diabetic lower extremity amputations in the univariate analysis. Conclusion. This study showed that the prevalences of diabetic foot ulcers and lower extremity amputations are high among diabetes patients. Foot deformities and previous history of foot ulcers are determinants of diabetic foot ulcers. Foot deformity and serum urea are associated with diabetic lower extremity amputations.
      PubDate: Mon, 11 Feb 2019 07:05:33 +000
  • Inflammation and Kidney Injury in Diabetic African American Men

    • Abstract: African Americans are disproportionately burdened by diabetic kidney disease (DKD). However, little is known about the cellular and molecular mechanisms underlying the onset and progression of DKD in this population. The goal of the current study was to determine the association between specific inflammation markers and kidney injury in diabetic African American men. To this end, we recruited diabetic patients either with () or without () diagnosed kidney disease along with age-matched nondiabetic controls (). Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFR) were used for biochemical assessment of kidney function. We then measured plasma and urinary levels of seven inflammatory markers, including adiponectin, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), TNF receptor 1 (TNFR1), TNF receptor 2 (TNFR2), interleukin-6 (IL-6), and intercellular cell adhesion molecule-1 (ICAM-1). Plasma levels of TNF-α, TNFR1, and TNFR2 were significantly higher in diabetics with macroalbuminuria compared to nondiabetic controls and diabetics with normoalbuminuria or microalbuminuria. Likewise, urinary levels of ICAM-1 were higher in diabetics with macroalbuminuria compared to the other groups. Indeed, urinary ICAM-1, plasma TNF-α, and adiponectin had moderate positive correlations with UACR while plasma TNFR1 and TNFR2 levels were strongly correlated with kidney injury, indicated by multiple biomarkers of kidney injury. In contrast, though plasma CRP was elevated in diabetic subjects relative to nondiabetic controls, its levels did not correlate with kidney injury. Together, these data suggest that inflammation, particularly that mediated by the TNF-α/NF-κB signaling axis, may play a role in the pathogenesis of DKD in African American men.
      PubDate: Tue, 05 Feb 2019 08:05:14 +000
  • Pioglitazone Ameliorates Atorvastatin-Induced Islet Cell Dysfunction
           through Activation of FFA1 in INS-1 Cells

    • Abstract: Increasing evidence shows that statins increase the risk of new-onset diabetes mellitus, but the exact mechanism is not clearly known. Free fatty acid receptor 1 (FFA1) has been recognized to mediate insulin secretion, and pioglitazone has direct effects on glucose-stimulated insulin secretion in addition to the reversion of insulin resistance. In this study, we found that atorvastatin decreased potassium-stimulated insulin secretion and inhibited the expression of FFA1, PDX-1, and BETA2/NeuroD in INS-1 cells. Further study demonstrated that pioglitazone prevented the impairment of insulin secretion induced by atorvastatin and enhanced the expression of FFA1, PDX-1, and BETA2/NeuroD reduced by atorvastatin in INS-1 cells. In addition, the preventive effect of pioglitazone on atorvastatin-induced impairment of insulin secretion and the enhancement of the expression of PDX-1 and BETA2/NeuroD was abolished by knockdown of FFA1 using siRNA or the PLC inhibitor, U-73122, respectively. Ultimately, FFA1 may mediate the atorvastatin-induced pancreatic β-cell dysfunction and pioglitazone may ameliorate this deleterious effect through the upregulation of FFA1 expression.
      PubDate: Sun, 03 Feb 2019 08:05:07 +000
  • Mangiferin Improved Palmitate-Induced-Insulin Resistance by Promoting Free
           Fatty Acid Metabolism in HepG2 and C2C12 Cells via PPARα: Mangiferin
           Improved Insulin Resistance

    • Abstract: Elevated free fatty acid (FFA) is a key risk factor for insulin resistance (IR). Our previous studies found that mangiferin could decrease serum FFA levels in obese rats induced by a high-fat diet. Our research was to determine the effects and mechanism of mangiferin on improving IR by regulating FFA metabolism in HepG2 and C2C12 cells. The model was used to quantify PA-induced lipid accumulation in the two cell lines treated with various concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased insulin-stimulated glucose uptake, via phosphorylation of protein kinase B (P-AKT), glucose transporter 2 (GLUT2), and glucose transporter 4 (GLUT4) protein expressions, and markedly decreased glucose content, respectively, in HepG2 and C2C12 cells induced by PA. Mangiferin significantly increased FFA uptake and decreased intracellular FFA and triglyceride (TG) accumulations. The activity of the peroxisome proliferator-activated receptor α (PPARα) protein and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1) and the fatty acid β-oxidation rate corresponding to FFA metabolism were also markedly increased by mangiferin in HepG2 and C2C12 cells. Furthermore, the effects were reversed by siRNA-mediated knockdown of PPARα. Mangiferin ameliorated IR by increasing the consumption of glucose and promoting the FFA oxidation via the PPARα pathway in HepG2 and C2C12 cells.
      PubDate: Sun, 27 Jan 2019 10:05:15 +000
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