Acute effects of GLP-1 on glucose uptake in obese subjects

体外研究表明，GLP-1是 脂肪和肌肉中的轻度拟胰岛素。我们做了一个研究， 非肥胖（即，非胰岛素抗性）受试者（发表于J. Clin. 年. Metab，1998年7月）静脉注射GLP-1， 并没有表现出这种现象。然而，由于受试者 正常的胰岛素作用，我们可能无法显示微妙的 拟胰岛素作用。因此，我们开始了一项研究， 非糖尿病（胰岛素抵抗，血糖正常）受试者 看看GLP-1是否能降低胰岛素抵抗。这将 还告诉我们GLP 1样化合物是否不仅可用于 糖尿病，但也在葡萄糖耐受不良。治疗方案， 目前可用于2型糖尿病的药物并不完美。绝 大多数2型糖尿病受试者在某些时候需要胰岛素， 因为β细胞功能恶化而失去生命项目 编号Z 01 AG 00214 -07 LCP显示，连续GLP-1 治疗可改善葡萄糖耐量， 啮齿动物的细胞更新。GLP-1，人皮下给药 在每餐之前，降低血糖。但是血糖水平 在下一次推注前再次升高。我们想看看GLP-1是否 持续皮下注射将使正常化并维持 血糖正常。因此，我们开始了一项研究， GLP-1通过Mini-Med泵连续皮下给药 （一个小泵的大小一个传呼机）到2型糖尿病 48小时的实验然后我们研究胰岛素分泌 能力和胰岛素敏感性。这些研究正在进行中。

Research done in vitro has shown that GLP-1 is mildly insulinomimetic in both fat and muscle. We did a study in non- obese (ie, not insulin resistant) subjects (published J. Clin. Endocrinol. Metab, July 1998) with intravenous GLP-1 and could not demonstrate this phenomenon. However, as the subjects had normal insulin action we may not have been able to show subtle insulinomimetic actions. We therefore initiated a study in obese, non diabetic (insulin resistant, with normal blood glucose) subjects to see if GLP-1 would decrease resistance to insulin. This would also tell us if a GLP 1-like compound might not only be useful in diabetes, but also in glucose intolerance. Treatment options that are presently available for type 2 diabetes are less than perfect. The vast majority of type 2 diabetic subjects require insulin at some point in their lives because of deteriorating beta cell function. Project Number Z01AG00214-07 LCP has shown that continuous GLP-1 treatment improves glucose tolerance and increases the rate of beta cell turnover in rodents. GLP-1, given subcutaneously to humans before each meal, does lower blood sugar. But blood sugar levels rise again before the next bolus. We wished to see if GLP-1 given continuously subcutaneously would normalize and maintain a normal blood sugar. We have, therefore, initiated a study whereby GLP-1 is given continuously subcutaneously, via a Mini-Med pump (a small pump about the size of a beeper) to Type 2 diabetic subjects for 48 hours. We then investigate for insulin-secretory capacity and insulin sensitivity. These studies are on-going.