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

胰高血糖素样肽-1（GLP-1）是一种天然产生的肽类激素 其在食物摄入后从空肠和髂骨分泌。是 在人类中最有效的促胰岛素剂，即，它能与 葡萄糖增加胰岛素分泌。相比之下， 在葡萄糖耐受状态下，GLP-1已被证明是 II型糖尿病受试者中的促胰岛素，与其他众所周知的 肠促胰岛素，葡萄糖依赖性促胰岛素肽（GIP）。此外，本发明还提供了一种方法， 几项研究表明GLP-1的独立作用类似于 即胰岛素，增强葡萄糖摄取能力不依赖于 它的促胰岛素作用。因此，GLP-1有可能成为一种 II型糖尿病状态的治疗剂。然而，在它成为 一个可以接受的治疗方法，需要做更多的基础工作。 到目前为止，已经进行了静脉输注GLP-1的研究 而且没有一个是长期输液的。我们给 通过渗透泵向动物皮下输注长达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。 我们建议将GLP-1 皮下注射至II型糖尿病受试者48小时，检查 胰岛素分泌和敏感性，在流感前后， 对葡萄糖的反应通过钳夹技术的方式传递。我们 先前进行了GLP-1静脉内短期（1小时）输注 并且不能证明胰腺外效应。到这个时候 影响，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 关于皮下递送的GLP-1是否是可行的 2型糖尿病的治疗方法

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.