Glucagon-like peptide 1 (GLP-1) and metabolic diseases.
Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone, mainly secreted after meals, which enhances glucose-induced insulin secretion and induces satiety. It has been reported that GLP-1 levels after a mixed meal and after an oral glucose load are reduced in patients with Type 2 diabetes. The reduction of oral glucose-stimulated active GLP-1 levels in patients with Type 2 diabetes has also been observed during euglycemic iperinsulinemic clamp. The reduction of post-prandial circulating active GLP-1 in Type 2 diabetic subjects, as a consequence of chronic hyperglycemia, could contribute to the reduction of early post-prandial insulin secretion; in fact, the administration of GLP-1 receptor antagonists to healthy volunteers elicits both an impairment of meal-induced insulin secretion and an increase of post-prandial glycemia similar to that observed in Type 2 diabetes. GLP-1 is rapidly inactivated by dipeptidyl peptidase IV (DPP-IV), an enzyme produced by endothelial cells in different districts and that circulates in plasma. It is still not clear whether the reduction of mealor oral-glucose stimulated GLP-1 levels in Type 2 diabetic patients is due to impairment of secretion, increase of degradation, or both. The major limitation of using GLP-1 to treat diabetic patients is the short half-life of the native compound. There are now several compounds in various stages of pre-clinical or clinical development for the treatment of Type 2 diabetes that utilize the GLP-1 signaling pathway; these include GLP-1 receptor agonists with extended half-lives, and inhibitors of DPP-IV that increase circulating levels of endogenous, intact and bioactive GLP-1.
Rotella
C M
CM
Section of Endocrinology, Department of Clinical Pathophysiology, University of Florence, Firenze, Italy. c.rotella@dfc.unifi.it
Pala
L
L
Mannucci
E
E
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism* / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D018027:Receptors, Glucagon / Q000819:agonists / Q000627:therapeutic use
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D011480:Protease Inhibitors; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4; D005947:Glucose