GLP-1 receptor agonists are growth and differentiation factors for pancreatic islet beta cells

Abstract

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that, when given exogenously, is capable of normalizing blood glucose in individuals with type 2 diabetes. Until recently most of the research on this compound had been related to its insulinotropic properties. However, GLP-1 also regulates insulin synthesis and proinsulin gene expression, as well as the components of the glucose-sensing machinery. In addition to regulating insulin release, it is involved in regulating the secretion of at least two other islet hormones--glucagon and somatostatin. Extraislet effects of GLP-1 include a role in the central nervous system stress response, hypothalamic-pituitary function, and the suppression of gastric emptying. Recent studies from our own and other laboratories show that GLP-1 can regulate islet growth and is a differentiation factor of the endocrine pancreas. This leads us to propose that GLP-1 and GLP-1 receptor agonists, in the context of long-term treatment of type 2 diabetes, will have broader biological action on the endocrine pancreas than was earlier anticipated. We propose that GLP-1 is a growth factor for pancreatic endocrine cells and can increase islet cell mass. Here we review those reports that have highlighted its role as a factor for islet cell growth and differentiation.