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.
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Authors | Alpana Bhattacharjee, Emma M Allister, Michael B Wheeler |
Journal | Canadian journal of physiology and pharmacology
(Can J Physiol Pharmacol)
Vol. 90
Issue 5
Pg. 663-8
(May 2012)
ISSN: 1205-7541 [Electronic] Canada |
PMID | 22530993
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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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
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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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