Glucagon-like peptide 1 secretion by the L-cell - The view from within

Glucagon-like peptide 1 (GLP-1) is a gut-derived peptide secreted from intestinal L-cells after a meal. GLP-1 has numerous physiological actions, including potentiation of glucose-stimulated insulin secretion, enhancement of beta-cell growth and survival, and inhibition of glucagon release, gastric emptying, and food intake. These antidiabetic effects of GLP-1 have led to intense interest in the use of this peptide for the treatment of patients with type 2 diabetes. Oral nutrients such as glucose and fat are potent physiological regulators of GLP-1 secretion, but non-nutrient stimulators of GLP-1 release have also been identified, including the neuromodulators acetylcholine and gastrin-releasing peptide. Peripheral hormones that participate in energy homeostasis, such as leptin, have also been implicated in the regulation of GLP-1 release. Recent studies have begun to elucidate the intracellular signaling pathways that mediate the effects of GLP-1 secretagogues on the intestinal L-cell. The purpose of this review is to summarize the known signaling mechanisms of GLP-1 secretagogues based on the available literature. A better understanding of the pathways underlying GLP-1 secretion may lead to novel approaches by which the levels of this important insulinotropic hormone can be enhanced in patients with type 2 diabetes.