The incretins: from the concept to their use in the treatment of type 2 diabetes. Part A: incretins: concept and physiological functions.
This paper briefly reviews the concept of incretins and describes the biological effects of the two incretins identified so far: the glucose-dependent insulinotropic polypeptide (GIP); and the glucagon-like peptide-1 (GLP-1). GIP is released by the Kcells of the duodenum, while GLP-1 is released by the Lcells of the distal ileum, in response to nutrient absorption. GIP and GLP-1 stimulate insulin biosynthesis and insulin secretion in a glucose-dependent manner. In addition, they increase beta-cell mass. GIP has a specific effect on adipose tissue to facilitate the efficient disposal of absorbed fat and, thus, may be involved in the development of obesity. GLP-1 has specific effects on pancreatic alpha cells, the hypothalamus, and gastrointestinal and cardiovascular systems. By inhibiting glucagon secretion and delaying gastric-emptying, GLP-1 plays an important role in glucose homoeostasis and, by inhibiting food intake, prevents the increase in body weight. As the metabolic effects of GIP are blunted in type 2 diabetes, this peptide cannot be used as an efficient therapy for diabetes. In contrast, GLP-1 effects are preserved at high concentrations in type 2 diabetes, making this peptide of great interest for the treatment of diabetes, a topic that will be discussed in the second part of this review.
Girard
J
J
CNRS UMR8104, InsermU567, département endocrinologie, métabolisme et cancer, université Paris-Descartes, institut Cochin, 24, rue du Faubourg-Saint-Jacques, 75014 Paris, France. gean.girard@inserm.fr
D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005746:Gastric Emptying / Q000502:physiology; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology / Q000502:physiology; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology / Q000502:physiology; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D054795:Incretins / Q000502:physiology / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050177:Overweight / Q000517:prevention & control; D018027:Receptors, Glucagon / Q000502:physiology
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D007328:Insulin; D018027:Receptors, Glucagon; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon