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In type 2 diabetes, chronic hyperglycemia is suggested to be detrimental to pancreatic beta cells, causing impaired insulin secretion. IL-1beta is a proinflammatory cytokine acting during the autoimmune process of type 1 diabetes. IL-1beta inhibits beta cell function and promotes Fas-triggered apoptosis in part by activating the transcription factor(More)
Insulin gene expression is restricted to islet beta cells of the mammalian pancreas through specific control mechanisms mediated in part by specific transcription factors. The protein encoded by the pancreatic and duodenal homeobox gene 1 (PDX-1) is central in regulating pancreatic development and islet cell function. PDX-1 regulates insulin gene expression(More)
Glucotoxicity and lipotoxicity contribute to the impaired beta-cell function observed in type 2 diabetes. Here we examine the effect of saturated and unsaturated fatty acids at different glucose concentrations on beta-cell proliferation and apoptosis. Adult rat pancreatic islets were cultured onto plates coated with extracellular matrix derived from bovine(More)
In autoimmune type 1 diabetes, Fas-to-Fas-ligand (FasL) interaction may represent one of the essential pro-apoptotic pathways leading to a loss of pancreatic beta-cells. In the advanced stages of type 2 diabetes, a decline in beta-cell mass is also observed, but its mechanism is not known. Human islets normally express FasL but not the Fas receptor. We(More)
Type 2 diabetes mellitus is increasing worldwide with a trend of declining age of onset. It is characterized by insulin resistance and a progressive loss of beta-cell function. The ability to secrete adequate amounts of insulin is determined by the functional integrity of beta-cells and their overall mass. Glucose, the main regulator of insulin secretion(More)
Bovine aortic endothelial and smooth-muscle cells down-regulate the rate of glucose transport in the face of hyperglycaemia, thus providing protection against deleterious effects of increased intracellular glucose levels. When exposed to high glucose concentrations these cells reduced the mRNA and protein content of their typical glucose transporter,(More)
The gerbil Psammomys obesus develops nutrition-dependent diabetes associated with moderate obesity. The disease is characterized by initial hyperinsulinemia, progressing to hypoinsulinemia associated with depleted pancreatic insulin stores. The contribution of changes in beta-cell turnover to insulin deficiency was investigated in vivo during transition to(More)
OBJECTIVE Mammalian target of rapamycin (mTOR) and its downstream target S6 kinase 1 (S6K1) mediate nutrient-induced insulin resistance by downregulating insulin receptor substrate proteins with subsequent reduced Akt phosphorylation. Therefore, mTOR/S6K1 inhibition could become a therapeutic strategy in insulin-resistant states, including type 2 diabetes.(More)
Hyperglycemia has been implicated in the pathogenesis of both micro- and macrovascular complications in diabetes. Little is known, however, about glucose transporters and their regulation in the vascular system. In this study, the regulation of glucose transporters by glucose was examined in cultured BAECs and BSMCs, and in human arterial smooth muscle(More)
Type 2 diabetes is characterized by insulin resistance and progressive beta-cell failure. Deficient insulin secretion, with increased proportions of insulin precursor molecules, is a common feature of type 2 diabetes; this could result from inappropriate beta-cell function and/or reduced beta-cell mass. Most studies using tissues from diabetic patients are(More)