Glucagon-like peptide 1 agonists and the development and growth of pancreatic β-cells

Abstract

Glucagon-like peptide 1 (GLP-1) is an intestine-derived insulinotropic hormone that stimulates glucose-dependent insulin production and secretion from pancreatic β-cells. Other recognized actions of GLP-1 are to suppress glucagon secretion and hepatic glucose output, delay gastric emptying, reduce food intake, and promote glucose disposal in peripheral tissues. All of these actions are potentially beneficial for the treatment of type 2 diabetes mellitus. Several GLP-1 agonists are in clinical trials for the treatment of diabetes. More recently, GLP-1 agonists have been shown to stimulate the growth and differentiation of pancreatic β-cells, as well as to exert cytoprotective, antiapoptotic effects on β-cells. Recent evidence indicates that GLP-1 agonists act on receptors on pancreas-derived stem/progenitor cells to prompt their differentiation into β-cells. These new findings suggest an approach to create β-cells in vitro by expanding stem/progenitor cells and then to convert them into β-cells by treatment with GLP-1. Thus GLP-1 may be a means by which to create β-cells ex vivo for transplantation into patients with insulinopenic type 1 diabetes and severe forms of type 2 diabetes.