GLP-1 EFFECTS ON INSULIN SECRETION AND SENSITIVITY IN TYPE II DIABETES

胰升糖素样肽-1(GLP-1)是一种天然产生的多肽激素 它是在进食后从空肠和回肠分泌的。它是 对人类最有效的胰岛素促进剂，即它与 葡萄糖能增加胰岛素的分泌。与之形成对比的是 胰岛素在糖耐量状态下，GLP-1已被证明是 与其他众所周知的糖尿病患者不同的是，II型糖尿病患者中的胰岛素敏感性 胰岛素、葡萄糖依赖的促胰岛素多肽(GIP)。此外, 几项研究表明，GLP-1与GLP-1类似 胰岛素，即不依赖于增强葡萄糖摄取的能力 它的胰岛素促进性作用。因此，GLP-1有可能成为 II型糖尿病状态的治疗剂。然而，在它成为 作为一种可以接受的治疗方法，还需要做更基础的工作。 到目前为止，研究是通过静脉输注GLP-1进行的 而且，没有一项是通过长期注入资金来完成的。我们已经给了 通过渗透泵向动物皮下输液，最长可达5天。我们 已经表明，GLP-1能够逆转与年龄相关的 Wistar大鼠体内的胰岛素分泌。它还能增加胰岛素 MRNA和总胰岛胰岛素含量。我们建议交付GLP-1 皮下注射给II型糖尿病患者48小时，检查 感染前后的胰岛素分泌和敏感性 对葡萄糖的响应通过钳位技术传递。我们 之前曾短暂(一小时)静脉注射GLP-1 并且不能表现出胰腺外效应。在这段时间里 我们应该能够果断地证明是否有 事实上，GLP-1的任何胰腺外效应。这会给你带来 关于皮下注射GLP-1是否可行的信息 治疗II型糖尿病的选择。

Glucagon-like peptide-1 (GLP-1) is a naturally produced peptide hormone which is secreted from the jejunum and ilium following food intake. It is the most potent insulinotropic agent in humans, i.e., it synergizes with glucose to augment insulin secretion. In contrast to the effects of incretins in glucose tolerant states, GLP-1 has been shown to be insulinotropic in Type II diabetic subjects, unlike the other well-known incretin, glucose-dependent insulinotropic peptide (GIP). In addition, several studies have implicated an independent role for GLP-1 similar to that of insulin, i.e., the ability to enhance glucose uptake independent of its insulinotropic effect. Thus, GLP-1 has the potential to be a therapeutic agent in Type II diabetic states. However, before it becomes an acceptable therapy, more basic work needs to be done. Studies so far have been carried out with intravenous infusions of GLP-1 and none have been done with long-term infusions. We have given subcutaneous infusions to animals for up to 5 days by osmotic pumps. We have shown that GLP-1 is capable of reversing the age-related decline in insulin secretion that occurs in Wistar rats. It also increases insulin mRNA and total islet insulin content. We propose to deliver GLP-1 subcutanelously to Type II diabetic subjects for 48 hours, checking insulin secretion and sensitivity, before and after the influsions, in response to glucose delivered by the way of clamp technology. We previously performed a short (one hour) influsion of GLP-1 intraveneously and were not able to demonstrate extrapancreatic effects. By this longer influsion, we should be able to decisively demonstrate whether there are in fact any extrapancreatic effects of the GLP-1. This will give information as to whether GLP-1 delivered subcutaneously is a viable option for trearing Type II diabetes.