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Diabetes Metab. 2008 Dec;34(6 Pt 1):550-9. doi: 10.1016/j.diabet.2008.09.001. Epub 2008 Nov 25.

The incretins: from the concept to their use in the treatment of type 2 diabetes. Part A: incretins: concept and physiological functions.

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1
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

Abstract

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.

PMID:
19036624
DOI:
10.1016/j.diabet.2008.09.001
[Indexed for MEDLINE]

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