Glucagon‐Like Peptide‐1: Actions and Influence on Pancreatic Hormone Function
Ellen Davis, Darleen A. Sandoval
Abstract
Abstract GLP‐1 was described as an incretin over 30 years ago. GLP‐1 is encoded by the preproglucagon gene ( Gcg ), which is expressed in the intestine, the pancreas, and the central nervous system. GLP‐1 activates GLP‐1 receptors (GLP‐1r) on the β‐cell to induce insulin secretion in a glucose‐dependent manner. GLP‐1 also inhibits α‐cell secretion of glucagon. As few, if any, GLP‐1r are expressed on α‐cells, indirect regulation, via β‐ or δ‐cell products has been thought to be the primary mechanism by which GLP‐1 inhibits glucagon secretion. However, recent work suggests that there is sufficient expression of GLP‐1r on α‐cells for direct regulation as well. Although the predominant source of circulating GLP‐1 is the intestine, the α‐cell becomes a source of GLP‐1 when the islet is metabolically stressed. Recent work suggests the possibility that this source of GLP‐1 is also be important in regulating nutrient‐induced insulin secretion in a paracrine fashion. More work is also accumulating regarding the role of glucagon, another Gcg ‐derived protein produced by the α‐cell, in stimulating insulin secretion by acting on GLP‐1r. Altogether, these data clearly demonstrate the important role of Gcg ‐derived peptides in regulating insulin secretion. Because of GLP‐1's important role in glucose homeostasis, it has been implicated in the success of bariatric surgery and has been successfully targeted for the treatment of type 2 diabetes mellitus. © 2020 American Physiological Society. Compr Physiol 10:577‐595, 2020.