Lindsay, JR, Duffy, NA, McKillop, Aine, Ardill, J, O'Harte, Finbarr, Flatt, Peter and Bell, PM (2005) Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2 diabetes. DIABETIC MEDICINE, 22 (5). pp. 654-657. [Journal article]
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Aims Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important insulinotropic hormones that enhance the insulin secretory response to feeding. Their potential for treating Type 2 diabetes is limited by short biological half-life owing to degradation by dipeptidyl peptidase IV (DPP IV). We investigated the acute effects of metformin on DPP IV activity in Type 2 diabetes to elucidate inhibition of DPP IV as a possible mechanism of action. Methods Eight fasting subjects with Type 2 diabetes (5M/3F, age 53.1 +/- 4.2 years, BMI 36.8 +/- 1.8 kg/m(2), glucose 8.9 +/- 1.2 mmol/l, HbA(1c) 7.8 +/- 0.6%) received placebo or metformin 1 g orally 1 week apart in a random, crossover design. Results Following metformin, DPP IV activity was suppressed compared with placebo (AUC(0-6 h) 3230 +/- 373 vs. 5764 +/- 504 nmol ml/l, respectively, P = 0.001). Circulating glucose, insulin and total GLP-1 were unchanged. Metformin also concentration-dependently inhibited endogenous DPP IV activity in vitro in plasma from Type 2 diabetic subjects. Conclusion Oral metformin effectively inhibits DPP IV activity in Type 2 diabetic patients, suggesting that the drug may have potential for future combination therapy with incretin hormones.
|Item Type:||Journal article|
|Faculties and Schools:||Faculty of Life and Health Sciences|
Faculty of Life and Health Sciences > School of Biomedical Sciences
|Research Institutes and Groups:||Biomedical Sciences Research Institute|
Biomedical Sciences Research Institute > Diabetes
|Deposited By:||Professor Peter Flatt|
|Deposited On:||18 Dec 2009 10:03|
|Last Modified:||28 Feb 2011 11:08|
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