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MK-626, a dipeptidyl peptidase-4 inhibitor, does not improve the hyperglycemia or hyperinsulinemia of nonobese diabetic MKR mice.

Abstract
Dipeptidyl peptidase-4 (DPP-4) inhibitors increase circulating levels of incretin hormones, which can enhance insulin secretion and β cell function. The aim of this study was to evaluate the effectiveness of MK-626 (a novel DPP-4 inhibitor) to reduce the hyperglycemia and hyperinsulinemia of nonobese type 2 diabetic MKR mice. Twelve to 14-week-old hyperglycemic MKR mice were gavaged daily with MK-626 (3 mg/kg body weight) or vehicle (0.5% methyl cellulose (MC)) for 2 weeks. MK-626-treated mice displayed no change in body weight or adverse reactions, suggesting good tolerance of the drug. Fed blood glucose was significantly reduced over the 2-week experiment; however, it was also reduced in the MC group, suggesting an effect of gavage alone. Fed plasma insulin and glucagon levels and glucose tolerance of MK-626-treated mice were similar to those of MC mice. Therefore, treatment with MK-626 did not correct the prolonged hyperglycemia and impaired glucose tolerance of MKR mice.
AuthorsAlpana Bhattacharjee, Emma M Allister, Michael B Wheeler
JournalCanadian journal of physiology and pharmacology (Can J Physiol Pharmacol) Vol. 90 Issue 5 Pg. 663-8 (May 2012) ISSN: 1205-7541 [Electronic] Canada
PMID22530993 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-(1,2,4)triazolo(1,5-a)pyridin-6-ylphenyl)butanamide
  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Incretins
  • Insulin
  • MK0626
  • Triazoles
  • Phenylalanine
  • Glucagon
  • Glucose
Topics
  • Animals
  • Blood Glucose (drug effects, metabolism)
  • Body Weight (drug effects)
  • Diabetes Mellitus, Experimental (blood, drug therapy, metabolism)
  • Dipeptidyl-Peptidase IV Inhibitors (pharmacology)
  • Glucagon (blood, metabolism)
  • Glucose (metabolism)
  • Glucose Intolerance (drug therapy, metabolism)
  • Homeostasis (drug effects)
  • Hyperglycemia (blood, drug therapy, metabolism)
  • Hyperinsulinism (blood, drug therapy, metabolism)
  • Incretins (blood, metabolism)
  • Insulin (blood, metabolism)
  • Insulin Secretion
  • Islets of Langerhans (drug effects, metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, Obese (blood, metabolism)
  • Phenylalanine (analogs & derivatives, pharmacology)
  • Triazoles (pharmacology)

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