Mechanisms of Action of the DPP-4 Inhibitor Vildagliptin in Man.
(2011) In Diabetes, Obesity and Metabolism 13(9). p.775-783- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2092704
- author
- Ahrén, Bo LU ; Schweizer, A. ; Dejager, S. ; Villhauer, E. B. ; Dunning, B. E. and Foley, J. E.
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- dipeptidyl peptidase-4, glucagon-like peptide-1, glucose-dependent, insulinotropic polypeptide, hypoglycaemia, insulin resistance, islet, function, type 2 diabetes mellitus
- in
- Diabetes, Obesity and Metabolism
- volume
- 13
- issue
- 9
- pages
- 775 - 783
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000293179200001
- scopus:79960831855
- pmid:21507182
- pmid:21507182
- ISSN
- 1462-8902
- DOI
- 10.1111/j.1463-1326.2011.01414.x
- language
- English
- LU publication?
- yes
- id
- 364cbd50-b10e-40e1-add0-fbe344e10c0c (old id 2092704)
- date added to LUP
- 2016-04-01 10:17:34
- date last changed
- 2024-02-21 13:10:50
@article{364cbd50-b10e-40e1-add0-fbe344e10c0c,
abstract = {{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.}},
author = {{Ahrén, Bo and Schweizer, A. and Dejager, S. and Villhauer, E. B. and Dunning, B. E. and Foley, J. E.}},
issn = {{1462-8902}},
keywords = {{dipeptidyl peptidase-4; glucagon-like peptide-1; glucose-dependent; insulinotropic polypeptide; hypoglycaemia; insulin resistance; islet; function; type 2 diabetes mellitus}},
language = {{eng}},
number = {{9}},
pages = {{775--783}},
publisher = {{Wiley-Blackwell}},
series = {{Diabetes, Obesity and Metabolism}},
title = {{Mechanisms of Action of the DPP-4 Inhibitor Vildagliptin in Man.}},
url = {{http://dx.doi.org/10.1111/j.1463-1326.2011.01414.x}},
doi = {{10.1111/j.1463-1326.2011.01414.x}},
volume = {{13}},
year = {{2011}},
}