Girard J
CNRS UMR8104, InsermU567, département endocrinologie, métabolisme et cancer, université Paris-Descartes, institut Cochin, 24, rue du Faubourg-Saint-Jacques, 75014 Paris, France.
Diabetes Metab. 2008 Dec;34(6 Pt 1):550-9. doi: 10.1016/j.diabet.2008.09.001. Epub 2008 Nov 25.
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.
本文简要回顾了肠促胰岛素的概念，并描述了目前已确定的两种肠促胰岛素的生物学效应：葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽-1（GLP-1）。十二指肠的K细胞释放GIP，而远端回肠的L细胞在营养物质吸收时释放GLP-1。GIP和GLP-1以葡萄糖依赖性方式刺激胰岛素生物合成和胰岛素分泌。此外，它们还能增加β细胞量。GIP对脂肪组织有特定作用，有助于有效处理吸收的脂肪，因此可能与肥胖的发生有关。GLP-1对胰腺α细胞、下丘脑以及胃肠和心血管系统有特定作用。通过抑制胰高血糖素分泌和延迟胃排空，GLP-1在葡萄糖稳态中起重要作用，并且通过抑制食物摄入来防止体重增加。由于GIP在2型糖尿病中的代谢效应减弱，该肽不能用作糖尿病的有效治疗药物。相比之下，GLP-1在2型糖尿病中高浓度时仍保留其效应，这使得该肽成为治疗糖尿病的一个备受关注的课题，这一主题将在本综述的第二部分进行讨论。
