EXENDIN-4 AS A TREATMENT FOR DIABETES MELLITUS

胰腺的β细胞，制造胰岛素， 2型糖尿病患者对葡萄糖的反应不正常。结合 尽管目前所有的治疗方法都可以用来治疗 随着时间的推移，β细胞功能继续恶化。与 英国《前瞻性》杂志目前提供的数据显示， 糖尿病研究（9月）1998年，这一点被带回家。 更有力。尽管对入组的患者进行了持续监测， 即使进行了密集的研究， 治疗，因为β细胞功能下降。我们一直 用GLP-1（一种天然存在的肽）研究了一段时间， 消化道对食物的反应产生并释放出来。它 增强β细胞的胰岛素释放能力， 食物令人感兴趣的是，在2型糖尿病患者中， 药理学剂量的GLP-1可以使血糖正常化，即， 达到了预期效果。然而，GLP-1具有生物半衰期 仅需2-4分钟，必须全身给药。这意味 必须持续地给予， 真的。吉拉怪兽是一种蜥蜴，它的自然栖息地是在 亚利桑那它在唾液中产生一种毒液， GLP-1，又称Exendin-4。当它被全身性地给予啮齿类动物时 其生物半衰期为12-16小时。我们给Exendin-4 腹腔内，每天一次，db/db小鼠，并显示， 血红蛋白A1 c是长期血糖控制的标志物， 在给药动物中为5.7%，在未给药动物中为9.1%。 我们正在扩大这个项目， Exendin-4是抗糖尿病的，我们正在研究 Exendin-4具有这种有益的长期机制， 方面的影响.我们已经获得了exendin-4的抗体， 测定以测量其在血浆中的浓度。一个 FDA的研究性IND刚刚批准给我们， 我们可以开始给糖尿病患者使用Exendin-4， 为了监测皮下给药后的疗效， 各种浓度。我们计划在下个月开始研究 年

Beta cells of the pancreas, which make insulin, do not respond normally to glucose in type 2 diabetes. In conjunction with this, and despite all treatments currently available to treat diabetes, beta cell function continues to deteriorate over time. With the data now available from the United Kingdom Prospective Diabetes Study (Sept. 1998) this point was brought home even more forcefully. Despite continual monitoring of patients enrolled in the study euglycemia could not be maintained, even with intensive therapy, because of declining beta cell function. We have been working for some time with GLP-1, a naturally occurring peptide, produced and released from the gut in response to food. It augments the insulin-releasing capacity of beta cells in response to food. Of great interest is the finding that in type 2 diabetes pharmacological doses of GLP-1 can normalize blood sugars, ie, euglycemia is achieved. However, GLP-1 has a biological half-life of only 2-4 minutes and has to be given systemically. This means that it would have to be given continuously in order to maintain euglycemia. The Gila monster is a lizard whose natural habitat is in Arizona. It produces a venom in its saliva which is a homolog of GLP-1, called Exendin-4. When it is given systemically to rodents its biological half-life is 12-16 hours. We gave Exendin-4 intraperitoneally, once daily, to db/db mice and showed that the hemoglobin A1c, a marker of long-term control of blood glucose, was 5.7% in the treated animals vs 9.1% in the non treated animals. We are expanding this project to find the minimal amount of Exendin-4 that is anti-diabetogenic and we are looking at the mechanisms whereby Exendin-4 has such beneficial long-term effects. We have obtained antibodies to exendin-4 so as to develop assays in order to measure its concentrations in plasma. An Investigational IND from the FDA has just been granted to us so that we can begin to administer Exendin-4 to diabetic subjects in order to monitor its efficacy after subcutaneous administration at various concentrations. We plan to begin the studies in the next year.