A mutated glucagon-like peptide-1 with improved glucose-lowering activity in diabetic mice

Abstract

Objectives The aim of this study was to characterize the conformation and potency of a mutated glucagon-like peptide-1 (mGLP-1), and evaluate its glucose-lowering activity in diabetic mice. Methods Spectroscopy techniques were employed to characterize the conformation of mGLP-1. Glucose tolerance test was performed to determine the potency of mGLP-1 in vivo. A mouse model in which diabetes was induced by multiple low doses of streptozotocin was established to evaluate the glucose-lowering activity of mGLP-1. Key findings Compared with native GLP-1, mGLP-1 had a similar conformation and an enhanced potency in vivo. In diabetic mice, mGLP-1 displayed a significantly improved glucose-lowering activity as judged by fasting glucose and insulin, oral glucose tolerance test, beta cell function analysis and histochemical analysis. Conclusions Collectively, mGLP-1 possesses an improved glucose-lowering activity in vivo and therefore can be recognized as a potential candidate for the future development of anti-diabetic drugs. © 2012 The Authors. JPP © 2012. Royal Pharmaceutical Society.