Coumaglutide, a novel long-acting GLP-1 analog, inhibits β-cell apoptosis in vitro and invokes sustained glycemic control in vivo

Glucagon-like peptide-1 (GLP-1) is a potential candidate for the treatment of type 2 diabetes. However, native GLP-1 is not suitable for therapy of diabetes due to its short half-life (t1/2=2 min). Our recent discovery of the novel long-acting GLP-1 analog, coumaglutide, elicits favorable hypoglycemic effects. The present study was aimed at determining the protection effect of β-cell from apoptosis and in vivo pharmacologic properties of coumaglutide in diabetic mice. To determine the protective effect of coumaglutide on INS-1 cell viability and apoptosis, cells were exposed to 1 μM streptozotocin (STZ) and coumaglutide for 24 h. Moreover, STZ-induced diabetic mice were treated daily with coumaglutide for 20 days and a range of pharmacologic parameters, including hemoglobin A1c (HbA1C), intraperitoneal glucose tolerance, food intake and body weight were assessed before and after the treatment. As with other glucagon-like peptide-1 receptor agonizts, coumaglutide was able to protect β-cell from apoptosis in vitro and induce a durable restoration of glycemic control (normalization of both HbA1C and improvement of intraperitoneal glucose tolerance) in diabetic mice. It can be concluded that coumaglutide retains native GLP-1 activities and thus may serve as a promising hypoglycemic drug candidate.

Our recent discovery of the novel long-acting GLP-1 analog, coumaglutide, protects β-cell from apoptosis in vitro and induces a durable restoration of glycemic control in diabetic mice. It can be concluded that coumaglutide retains native GLP-1 activities and thus may serve as a promising hypoglycemic drug candidate.Figure optionsDownload high-quality image (183 K)Download as PowerPoint slide