Biochemical and Biophysical Research Communications
Reduced serum dipeptidyl peptidase-IV after metformin and pioglitazone treatments
Section snippets
Chemicals
Metformin (1,1-dimethylbiguanide hydrochloride, Catalog # D5035) and glyburide (Catalog # G-0639) were obtained from Sigma (St. Louis, MO 63178) and pioglitazone, GW7845, and LAF237 were from GlaxoSmithKline chemical storage.
In vivo studies
Animals. All studies were conducted using age- and weight-matched male ZDF fa/fa rats (Genetic Models, Indianapolis, IN) or db/db mice (Jackson Labs) housed at 72 °F and 50% relative humidity with a 12 h light/dark cycle. Rats were fed PMI 5008 Formulab Diet (PMI Nutrition
Effects of treatment on serum DPP-IV activity, glucose, glycosylated hemoglobin, GLP-1, and insulin levels
ZDF rats represent an animal model of non-insulin-dependent diabetes that are characterized by profound insulin resistance, insulin hypersecretion, and obesity. To investigate whether altered glycemic control affects DPP-IV activity in vivo, ZDF rats at 6.5 and 8.5 weeks of age were treated with vehicle, glyburide, metformin or pioglitazone for 2 weeks. DPP-IV activity, glycosylated hemoglobin and glucose levels were 218%, 52%, and 84% greater (P < 0.05), respectively, in serum from the older
Discussion
While Mannucci et al. [11] reported that metformin inhibits serum DPP-IV in vitro, Yasuda et al. [12] and Hinke et al. [13] reported that metformin is not a competitive inhibitor of DPP-IV. Our results also demonstrate metformin and piogitazone are not competitive inhibitors of DPP-IV activity in vitro. Moreover, we show pioglitazone or metformin treatment lowered serum DPP-IV activity and glucose levels, whereas glyburide was ineffective. Although DPP-IV activity was reduced in serum after
Acknowledgments
We thank Jane Binz, Daphne Clancy, John Hughes, Shelby Martenson, and Tracy Brainard for technical support.
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