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• W1932403114 abstract "Vildagliptin is a potent, selective and reversible inhibitor of dipeptidyl peptidase-4 (DPP-4), the enzyme responsible for rapid inactivation of the incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP). GLP-1 and GIP are important for the maintenance of normal glucose homeostasis as they enhance the sensitivity of insulin (beta-cell) and glucagon (alpha-cell) secretion to glucose. The delicate balance that is achieved by the incretin hormones is disturbed in type 2 diabetes mellitus (T2DM). Mechanistic studies of vildagliptin performed to characterise the effects of DPP-4 inhibition on pancreatic islet function and glucose metabolism have found that vildagliptin produces dose-dependent reductions in DPP-4; these result in persistent levels of active GLP-1 and GIP in the circulation leading to improved beta-cell sensitivity to glucose and glucose-dependent insulin secretion, and improved alpha-cell sensitivity to glucose and reduction in inappropriate glucagon secretion. These islet effects in turn lead to a reduction of the inappropriate endogenous glucose production and glucose utilisation during meals, resulting in improved glucose tolerance, and to a reduction of the inappropriate endogenous glucose production during the postabsorptive period that contributes to a reduced fasting hyperglycaemia. These islet effects are associated with improved insulin sensitivity and reduced meal-related hypertriglyceridaemia. In contrast, the GLP-1 effect of significantly delaying gastric emptying was not evident with vildagliptin treatment. The metabolic benefits of vildagliptin observed in T2DM are also evident in subjects with impaired glucose tolerance. Hence, vildagliptin improves glucose metabolism mainly by improving islet function." @default.
• W1932403114 created "2016-06-24" @default.
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• W1932403114 date "2008-02-05" @default.
• W1932403114 modified "2023-09-23" @default.
• W1932403114 title "The islet enhancer vildagliptin: mechanisms of improved glucose metabolism" @default.
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• W1932403114 doi "https://doi.org/10.1111/j.1742-1241.2007.01685.x" @default.
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