Enteroinsular signaling: perspectives on the role of the gastrointestinal hormones glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide in normal and abnormal glucose metabolism.

Abstract

The gastrointestinal hormones glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide are emerging as essential regulators of insulin secretion and glucose homeostasis. These peptides, termed incretins, are the key intermediaries in a system that links the absorption of nutrients in the gut with important metabolic processes in substrate assimilation. New findings indicate that the enteroinsular system mediated by the incretins is relevant to both the pathophysiology and treatment of diabetes. Important advances have been made in the understanding of mechanisms fundamental to incretin function such as their release from the intestine during meals, their actions on beta-cell secretion, and extrapancreatic effects. In addition, the regulation of islet growth by glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide is a novel area with considerable support from recent studies. Abnormalities of incretin function are present in patients with diabetes and current research has implicated specific defects of both glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide action in diabetes. Finally, several pharmacological applications of the incretin signaling pathways are under active investigation for the treatment of diabetes. With the intensified research of the last several years the physiologic importance of the incretins has been clarified. Enteroinsular signaling is an essential component of the metabolic processes that govern carbohydrate, and likely other nutrient metabolism. As a pathophysiology of the incretins emerges, glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide will have increasing clinical relevance. This is currently exemplified by the development of therapeutics for diabetes that work through the incretin signaling pathways.