Vascular Effects of Sitagliptin in Diabetes Mellitus
Status:
Unknown status
Trial end date:
2012-12-01
Target enrollment:
Participant gender:
Summary
Glucagon-like peptide 1 (GLP-1) is a 30-amino acid gut hormone secreted in a
nutrient-dependent manner that stimulates insulin secretion and inhibits glucagon secretion
and gastric emptying, thereby reducing postprandial glycemia.1,2 GLP-1 is derived from
posttranslational proteolysis of preproglucagon, and its peptide sequence is identical in
mouse, rat, and human.2,3 After secretion from enteroendocrine L cells, GLP-1(7-36) amide is
rapidly degraded by dipeptidyl peptidase-4 (DPP-4) to its N-terminally truncated metabolite
GLP-1(9-36), which does not interact with the known GLP-1 receptor.4,5 The diverse actions of
GLP-1 include the proliferation, differentiation, and protection from apoptosis of pancreatic
β cells and the induction of satiety. GLP-1 also improves memory and learning, stimulates
afferent sensory nerves, and has neuroprotective functions.1,6 Furthermore, GLP-1 receptor
agonists have been reported to have cardiac and vascular actions in rodents and humans that
include effects on contractility, blood pressure, cardiac output,7-10 and
cardioprotection.11-14