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Pancreatic ?-cells secrete the hormone insulin, which is essential to maintain systemic glucose homeostasis. ?-Cell insufficiency due to impaired function, loss of identity, and increased cell death is central to the pathogenesis of diabetes. ?-Cells in adult life are postmitotic, with a limited (...)
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Recent reports have revived interest in the active role that ?-cells may play in type 1 diabetes pathogenesis at different stages of disease. In some studies, investigators suggested an initiating role and proposed that type 1 diabetes may be primarily a disease of ?-cells and only secondarily a (...)
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Understanding how insulin secretion is regulated and how the ?-cells and islets become dysfunctional is critical to understanding and treating diabetes. The islets of Langerhans are highly vascularized, receiving ?10–20% of the pancreas blood flow (as measured by microbead accumulation) despite (...)
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The extracellular matrix (ECM) not only provides a structural support network for the assembly of individual cells into tissues but also affects growth, recruitment, differentiation, and function of the composing cells. In obesity, adipose tissue ECM undergoes remodeling, with dramatic changes (...)
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Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications, affecting 2–22% of all pregnancies depending on diagnostic criteria and study populations (1). GDM reflects an increased risk of type 2 diabetes (T2D) and cardiovascular diseases after the index pregnancy in (...)
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For the past 26 years, the American Diabetes Association and its professional constituents have had the great pleasure of working with Lynda (“Lyn”) Reynolds, the director of the ADA Editorial Office. Lyn first joined ADA’s publishing team in 1997, when she was hired by editor in chief Charles M. (...)
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In Fig. 3B of article cited above, for images of iWAT and eWAT, the labels “WT” and “LKO” were inadvertently transposed. LKO (Cpt1a knockout) should have been the label for the first set of images of adipose tissue, and WT (wild type) should have been the label for the second set of (...)
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Thymic presentation of self-antigens is critical for establishing a functional yet self-tolerant T-cell population. Hybrid peptides formed through transpeptidation within pancreatic ?-cell lysosomes have been proposed as a new class of autoantigens in type 1 diabetes (T1D). While the production (...)
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Preclinical rodent and nonhuman primate models investigating maternal obesity have highlighted the importance of the intrauterine environment in the development of insulin resistance in offspring; however, it remains unclear if these findings can be translated to humans. To investigate possible (...)
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Transient insulin deprivation with concurrent hyperglucagonemia is a catabolic state that can occur in type 1 diabetes. To evaluate glucagon’s catabolic effect in the setting of its glucogenic effect, we measured the regional exchanges of amino acid metabolites (amino-metabolites) across muscle (...)
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We systematically investigated the bidirectional causality among HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), triglycerides (TGs), fasting insulin (FI), and glycated hemoglobin A1c (HbA1c) based on genome-wide association summary statistics of Europeans (n = 1,320,016 for lipids, 151,013 (...)
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Diabetes can damage both the peripheral sensory organs, causing retinopathy, and the central visual system, leading to contrast sensitivity and impaired color vision in patients without retinopathy. Orientation discrimination is important for shape recognition by the visual system. Our (...)
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We evaluated the role of the p66Shc redox adaptor protein in pancreatic ?-cell insulin resistance that develops under lipotoxic conditions and with excess body fat. Prolonged exposure to palmitate in vitro or the presence of overweight/obesity augmented p66Shc expression levels and caused an (...)
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In this cross-sectional study we aimed to quantify the somatosensory dysfunction in the hand in people with diabetes with distal symmetrical polyneuropathy (DSPN) in hands and explore early signs of nerve dysfunction in people with diabetes without DSPN in hands. The clinical diagnosis of DSPN (...)
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Hypoxia-induced islet cell death, caused by an insufficient revascularization of the grafts, is a major obstacle for successful pancreatic islet transplantation. Recently, it has been reported that the nucleotide-binding oligomerization domain–like receptor protein 3 (NLRP3) inflammasome is (...)
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The pancreatic islet depends on blood supply to efficiently sense plasma glucose levels and deliver insulin and glucagon into the circulation. Long believed to be passive conduits of nutrients and hormones, islet capillaries were recently found to be densely covered with contractile pericytes (...)
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Bariatric surgery improves glucose homeostasis, but the underlying mechanisms are not fully elucidated. Here, we show that the expression of sodium–glucose cotransporter 2 (SGLT2/Slc5a2) is reduced in the kidney of lean and obese mice following vertical sleeve gastrectomy (VSG). Indicating an (...)
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Prevention of immune rejection without immunosuppression is the ultimate goal of transplant immunobiology. One way to achieve this in cellular transplantation, such as with islet transplantation, is to create a favorable local environment at the transplant site. In the current study, we found (...)
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Patients with type 2 diabetes have a substantial risk of developing cardiovascular disease. Phosphodiesterase 4 (PDE4) dysregulation is of pathophysiological importance in metabolic disorders. For determination of the role of PDE4 in diabetic cardiac dysfunction, mice fed with a high-fat diet (...)
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Identifying the mechanisms behind the ?-cell adaptation to failure is important to develop strategies to manage type 2 diabetes (T2D). Using db/db mice at early stages of the disease process, we took advantage of unbiased RNA sequencing to identify genes/pathways regulated by insulin resistance (...)
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Apolipoprotein M (apoM), primarily carried by HDL, has been associated with several conditions, including cardiovascular disease and diabetic nephropathy. This study proposes to examine whether plasma apoM levels are associated with the development of diabetic kidney disease, assessed as (...)
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Patients with type 1 diabetes (T1D) may develop severe outcomes during coronavirus disease 2019 (COVID-19), but their ability to generate an immune response against the SARS-CoV-2 mRNA vaccines remains to be established. We evaluated the safety, immunogenicity, and glycometabolic effects of the (...)
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Gestational diabetes mellitus (GDM) predisposes pregnant individuals to perinatal complications and long-term diabetes and cardiovascular diseases. We developed and validated metabolomic markers for GDM in a prospective test-validation study. In a case-control sample within the PETALS cohort (...)
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Dysregulation of extracellular matrix proteins in obese adipose tissue (AT) induces systemic insulin resistance. The metabolic roles of type VI collagen and its cleavage peptide endotrophin in obese AT are well established. However, the mechanisms regulating endotrophin generation remain (...)