Ingested nutrients stimulate gastrointestinal secretion of glucagon-like peptide-1 (GLP-1), among other hormones to regulate metabolism. GLP-1 stimulates pancreatic islet secretion of insulin. Because the activity of GLP-1 is mostly retained in patients with type 2 diabetes, there has been considerable interest in increasing GLP-1 activity via analogs or inhibition of the dipeptidyl peptidase-4 (DPP-4) that degrades GLP-1. α-Glucosidase is an enzyme required for carbohydrate digestion in the gut, and inhibitors of α-glucosidase are used clinically in patients with type 2 diabetes. Although it has been observed that the inhibitors increase GLP-1 levels, the underlying mechanism of this cross-talk has been poorly understood. In this issue, Moritoh et al., describe a study on increased GLP-1 secretion in obese diabetic ob/ob mice after treatment with the α-glucosidase inhibitor voglibose [5-(1,3-dihydroxypropan-2-ylamino)-1-(hydroxymethyl)cyclohexane-1,2,3,4-tetrol]. They evaluated changes in plasma GLP-1 and DPP-4 activity and gut GLP-1-related gene expression of glucagon after acute or chronic voglibose treatment. They found that 1-day treatment increased plasma GLP-1 without affecting DPP-4 activities and that longer treatments (3-4 weeks) also increased plasma GLP-1 while now decreasing DPP-4 activity. They also learned that GLP-1 levels and related gut glucagon expression were increased in the lower intestine and colon after chronic treatment. The authors conclude that increased plasma GLP-1 was a result of increased GLP-1 expression and secretion coupled with decreased DPP-4 activity. The novel findings of this study show that the acute and chronic effects of α-glucosidase inhibition on DPP-4 and on gut GLP-1 content differ, suggesting that agents such as voglibose have added utility in the management of type 2 diabetes.
See article at J Pharmacol Exp Ther 2009, 329:669-676.
- The American Society for Pharmacology and Experimental Therapeutics