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The incretins: from the concept to their use in the treatment of type 2 diabetes Part A: incretins: concept and physiological functions Girard JDiabetes Metab 2008[Dec]; 34 (6 Pt 1): 550-9This 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.|Adipose Tissue/drug effects/physiology/physiopathology[MESH]|Body Weight/drug effects/physiology[MESH]|Diabetes Mellitus, Type 2/*drug therapy[MESH]|Gastric Emptying/physiology[MESH]|Gastric Inhibitory Polypeptide/pharmacology/physiology[MESH]|Glucagon-Like Peptide 1/pharmacology/physiology[MESH]|Glucagon-Like Peptide-1 Receptor[MESH]|Glucagon/antagonists & inhibitors/metabolism[MESH]|Humans[MESH]|Incretins/physiology/*therapeutic use[MESH]|Insulin Secretion[MESH]|Insulin/*metabolism[MESH]|Overweight/prevention & control[MESH]|Receptors, Glucagon/physiology[MESH] |
