Glucagon-like peptide 1: continued advances, new targets and expanding promise as a model therapeutic.
OBJECTIVE
This article discusses glucagon-like peptide 1 physiology and its various sites of action beyond the incretin effect and highlights recent findings (2005 and 2006).


RESULTS
Glucagon-like peptide 1 is a physiological incretin in humans and promotes insulin secretion after nutrient ingestion. It is secreted from intestinal L cells after meals and may be partially responsible for the improved glycemic control and weight loss after bariatric surgery. In vivo, glucagon-like peptide 1 is quickly degraded by dipetidyl peptidase IV to glucagon-like peptide 1(9-36), which has unclear physiologic activity. Glucagon-like peptide 1 and its specific receptor are also expressed in the brain, and central nervous system. Glucagon-like peptide 1 can reduce food intake, mediate toxic illness responses and control muscle and liver glucose disposal. In the heart, glucagon-like peptide 1 receptor activation improves cardiac hemodynamics in patients following angioplasty and has a beneficial effect on myocardial function in heart failure and postischemic animal models. Finally, glucagon-like peptide 1 augments islet mass and recent studies have identified cellular mechanisms by which glucagon-like peptide 1 receptor signaling affects this process.


CONCLUSIONS
Glucagon-like peptide 1 is emerging as a regulatory factor with a broad range of actions related to substrate and energy metabolism. With the recent development of medications based on glucagon-like peptide 1 receptor signaling for diabetes treatment, these new findings suggest the promise of further application of this system for the treatment of other conditions such as obesity and cardiovascular disease.
Aulinger
Benedikt
B
Division of Endocrinology, University of Cincinnati, Cincinnati, Ohio 45267, USA.
D'Alessio
David
D
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy; D004734:Energy Metabolism / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism / Q000502:physiology*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007413:Intestinal Mucosa / Q000378:metabolism; D009747:Nutritional Physiological Phenomena; D018027:Receptors, Glucagon / Q000378:metabolism; D015398:Signal Transduction
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1