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Mechanisms of Actio...
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Ahrén, BoLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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Mechanisms of Action of the DPP-4 Inhibitor Vildagliptin in Man.
- Article/chapterEnglish2011
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LIBRIS-ID:oai:lup.lub.lu.se:364cbd50-b10e-40e1-add0-fbe344e10c0c
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https://lup.lub.lu.se/record/2092704URI
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https://doi.org/10.1111/j.1463-1326.2011.01414.xDOI
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Language:English
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Summary in:English
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Inhibition of dipeptidyl peptidase-4 (DPP-4) by vildagliptin prevents degradation of glucagon-like peptide-1 (GLP-1) and reduces glycemia in type 2 diabetes, with low risk for hypoglycemia and no weight gain. Vildagliptin binds covalently to the catalytic site of DPP-4, eliciting prolonged enzyme inhibition. This raises intact GLP-1 levels, both after meal ingestion and in the fasting state. Vildagliptin has been shown to stimulate insulin secretion and to inhibit glucagon secretion in a glucose-dependent manner. At hypoglycemic levels, the counterregulatory glucagon response is enhanced relative to baseline by vildagliptin. Vildagliptin also inhibits hepatic glucose production, mainly through changes in islet hormone secretion, and improves insulin sensitivity, as determined with a variety of methods. These effects underlie the improved glycemia with low risk for hypoglycemia. Vildagliptin also suppresses postprandial triglyceride-rich lipoprotein levels after ingestion of a fat-rich meal and reduces fasting lipolysis, suggesting inhibition of fat absorption and reduced triglyceride stores in non-fat tissues. The large body of knowledge on vildagliptin regarding enzyme binding, incretin and islet hormone secretion and glucose and lipid metabolism is summarized, with discussion of the integrated mechanisms and comparison with other DPP-4 inhibitors and GLP-1 receptor activators, where appropriate.
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Schweizer, A.
(author)
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Dejager, S.
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Villhauer, E. B.
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Dunning, B. E.
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Foley, J. E.
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Medicin, LundSektion II
(creator_code:org_t)
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In:Diabetes, Obesity and Metabolism: Wiley13:9, s. 775-7831462-8902
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