Mechanisms of action of the dipeptidyl peptidase-4 inhibitor vildagliptin in humans
| Autor: | Sylvie Dejager, E. B. Villhauer, Anja Schweizer, B. E. Dunning, Bo Ahrén, James E. Foley |
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| Rok vydání: | 2011 |
| Předmět: |
endocrine system
medicine.medical_specialty business.industry Endocrinology Diabetes and Metabolism digestive oral and skin physiology Glucagon secretion Incretin Dipeptidyl peptidase-4 inhibitor medicine.disease Glucagon-like peptide-1 Enzyme binding Endocrinology Insulin resistance Internal medicine Internal Medicine Medicine Vildagliptin business hormones hormone substitutes and hormone antagonists Dipeptidyl peptidase-4 medicine.drug |
| Zdroj: | Diabetes, Obesity and Metabolism. 13:775-783 |
| ISSN: | 1462-8902 |
| DOI: | 10.1111/j.1463-1326.2011.01414.x |
| Popis: | Inhibition of dipeptidyl peptidase-4 (DPP-4) by vildagliptin prevents degradation of glucagon-like peptide-1 (GLP-1) and reduces glycaemia in patients with type 2 diabetes mellitus, with low risk for hypoglycaemia 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 inhibit glucagon secretion in a glucose-dependent manner. At hypoglycaemic 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 glycaemia with low risk for hypoglycaemia. Vildagliptin also suppresses postprandial triglyceride (TG)-rich lipoprotein levels after ingestion of a fat-rich meal and reduces fasting lipolysis, suggesting inhibition of fat absorption and reduced TG 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. |
| Databáze: | OpenAIRE |
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