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Mechanisms of Action of the DPP-4 Inhibitor Vildagliptin in Man.

Ahrén, Bo LU ; Schweizer, A.; Dejager, S.; Villhauer, E. B.; Dunning, B. E. and Foley, J. E. (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)
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author
organization
publishing date
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
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
2011-05-02 15:17:56
date last changed
2017-10-01 03:11:58
@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},
  keyword      = {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},
  volume       = {13},
  year         = {2011},
}