Vilsbøll T, Holst J J
Department of Internal Medicine F, Gentofte University Hospital, Gentofte, Denmark.
Department of Internal Medicine F, Gentofte University Hospital, Niels Andersensvej 65, 2900, Hellerup, Denmark.
Diabetologia. 2004 Mar;47(3):357-366. doi: 10.1007/s00125-004-1342-6. Epub 2004 Feb 13.
When glucose is taken orally, insulin secretion is stimulated much more than it is when glucose is infused intravenously so as to result in similar glucose concentrations. This effect, which is called the incretin effect and is estimated to be responsible for 50 to 70% of the insulin response to glucose, is caused mainly by the two intestinal insulin-stimulating hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Their contributions have been confirmed in mimicry experiments, in experiments with antagonists of their actions, and in experiments where the genes encoding their receptors have been deleted. In patients with Type 2 diabetes, the incretin effect is either greatly impaired or absent, and it is assumed that this could contribute to the inability of these patients to adjust their insulin secretion to their needs. In studies of the mechanism of the impaired incretin effect in Type 2 diabetic patients, it has been found that the secretion of GIP is generally normal, whereas the secretion of GLP-1 is reduced, presumably as a consequence of the diabetic state. It might be of even greater importance that the effect of GLP-1 is preserved whereas the effect of GIP is severely impaired. The impaired GIP effect seems to have a genetic background, but could be aggravated by the diabetic state. The preserved effect of GLP-1 has inspired attempts to treat Type 2 diabetes with GLP-1 or analogues thereof, and intravenous GLP-1 administration has been shown to be able to near-normalize both fasting and postprandial glycaemic concentrations in the patients, perhaps because the treatment compensates for both the impaired secretion of GLP-1 and the impaired action of GIP. Several GLP-1 analogues are currently in clinical development and the reported results are, so far, encouraging.
口服葡萄糖时，胰岛素分泌受到的刺激比静脉输注葡萄糖时要大得多，从而导致相似的血糖浓度。这种效应被称为肠促胰岛素效应，据估计它对胰岛素对葡萄糖的反应贡献了50%至70%，主要由两种肠道促胰岛素激素引起，即胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性促胰岛素多肽（GIP）。它们的作用在模拟实验、其作用拮抗剂的实验以及编码其受体的基因被删除的实验中得到了证实。在2型糖尿病患者中，肠促胰岛素效应要么严重受损，要么缺失，据推测这可能导致这些患者无法根据自身需求调节胰岛素分泌。在对2型糖尿病患者肠促胰岛素效应受损机制的研究中发现，GIP的分泌通常正常，而GLP-1的分泌减少，这可能是糖尿病状态的结果。更重要的可能是GLP-1的效应得以保留，而GIP的效应严重受损。GIP效应受损似乎有遗传背景，但可能会因糖尿病状态而加重。GLP-1效应的保留激发了用GLP-1或其类似物治疗2型糖尿病的尝试，静脉注射GLP-1已被证明能够使患者的空腹和餐后血糖浓度接近正常，这可能是因为该治疗弥补了GLP-1分泌受损和GIP作用受损的问题。目前有几种GLP-1类似物正在进行临床开发，到目前为止所报道的结果令人鼓舞。
