Gastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogenesis of type 2 diabetes
Gastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogenesis of type 2 diabetes
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DOI：
10.2337/diabetes.53.suppl_3.s190
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发表时间：
2004-12-01
期刊：
影响因子：
7.7
通讯作者：
Meier, JJ
中科院分区：
文献类型：
--
作者：
Nauck, MA;Baller, B;Meier, JJ
肠促胰岛素效应表明口服葡萄糖比静脉注射葡萄糖引起更高的胰岛素反应。负责肠促胰岛素作用的两种激素，葡萄糖依赖性胰岛素促胰岛素激素（GIP）和胰高血糖素样肽-1 (GLP-1)，在口服葡萄糖负荷后分泌，并在高血糖反应中增加胰岛素分泌。在2型糖尿病患者中，肠促胰岛素作用降低，存在中度GLP-1分泌不足。然而，对GLP-1的胰岛素促胰岛素反应在2型糖尿病中得到很好的维持。2型糖尿病患者的GIP分泌正常或高分泌；然而，内分泌胰腺对GIP的反应性大大降低。在大约50%的2型糖尿病患者的一级亲属中，可以观察到外源性GIP对胰岛素的影响类似地降低，口服葡萄糖后GIP或GLP-1的分泌没有明显改变。这开启了一种可能性，即对GIP反应性降低是2型糖尿病发病机制的早期步骤。另一方面，这为利用肠促胰岛素激素，特别是GLP-1及其衍生物，替代肠促胰岛素介导的胰岛素分泌不足，治疗2型糖尿病提供了基础。
The incretin effect denominates the phenomenon that oral glucose elicits a higher insulin response than does intravenous glucose. The two hormones responsible for the incretin effect, glucose-dependent insulinotropic hormone (GIP) and glucagon-like peptide-1 (GLP-1), are secreted after oral glucose loads and augment insulin secretion in response to hyperglycemia. In patients with type 2 diabetes, the incretin effect is reduced and there is a moderate degree of GLP-1 hyposecretion. However, the insulinotropic response to GLP-1 is well maintained in type 2 diabetes. GIP is secreted normally or hypersecreted in type 2 diabetes; however, the responsiveness of the endocrine pancreas to GIP is greatly reduced. In similar to50% of first-degree relatives of patients with type 2 diabetes, similarly reduced insulinotropic responses toward exogenous GIP can be observed, without significantly changed secretion of GIP or GLP-1 after oral glucose. This opens the possibility that a reduced responsiveness to GIP is an early step in the pathogenesis of type 2 diabetes. On the other hand, this provides a basis to use incretin hormones, especially GLP-1 and its derivatives, to replace a deficiency in incretin-mediated insulin secretion in the treatment of type 2 diabetes.