Voglibose, an Alpha-glucosidase Inhibitor, to Increase Active Glucagon-like Peptide-1 Levels

Voglibose is an alpha-glucosidase inhibitor used for lowering post-prandial blood glucose levels in patients with diabetes mellitus. Voglibose is known for its ability to increase glucagon-like peptide-1 (GLP-1) secretion in humans. Our recent study demonstrated new mechanisms by which voglibose increases plasma active GLP-1 levels in diabetic ob/ob mice. As expected, the stimulatory effects of voglibose on GLP-1 secretion resulted in increased active GLP-1 levels in plasma in the 1day dosing study. Unexpectedly, chronic but not 1day treatment with voglibose decreased plasma dipeptidyl peptidase-4 (DPP-4) activity by reducing its circulating protein levels. We have also revealed that chronic dosing of voglibose increased Neurod1 and Glucagon gene expression, and GLP1 content in the lower gut. Active GLP-1 levels in plasma achieved by chronic treatment with voglibose were higher than those achieved by 1day treatment. In the present overview, by using acarbose, another alpha-glucosidase inhibitor with different selectivity, as a comparator, we demonstrated that inhibition of alpha-glucosidase induces a decrease in plasma DPP-4 activity in ob/ob mice. Notably, compared to acarbose, voglibose has demonstrated more favorable effects on DPP-4 activity, GLP-1 secretion and gut GLP-1 content, when glucose levels were equally improved, leading to higher plasma active GLP-1 levels. These findings provide new insights into _______________________ Received 08/10/09; accepted 09/11/09 Correspondence: Yusuke Moritoh, Pharmacology Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 17-85, Jusohonmachi 2-chome, Yodogawa-ku, Osaka 532-8686, Japan. Tel. 816-6300–6764, Fax. 81-6-6300-6306. e-mail: [email protected] the mechanism underlying the increases in active GLP-1 circulation by voglibose.