Byrne M M, Göke B
Department of Internal Medicine, Philipps University, Marburg, Germany.
Diabet Med. 1996 Oct;13(10):854-60. doi: 10.1002/(SICI)1096-9136(199610)13:10<854::AID-DIA262>3.0.CO;2-E.
So far, a wealth of data originating from in vitro or animal experiments has been collected supporting the concept that the gut hormone, glucagon-like peptide-1 (GLP-1) may serve as a model molecule for the design of a new drug for the treatment of diabetes mellitus. This is supported by observations that GLP-1 has potent insulinotropic action in patients with non-insulin-dependent diabetes mellitus (NIDDM). It enhances beta-cell sensitivity to glucose stimulated insulin secretion. GLP-1 may also have a role in the treatment of impaired glucose tolerance, where the beta-cell is already insensitive to changes in plasma glucose concentrations. It may, as has previously been shown in animal models of 'prediabetes', delay the progressive decline in glucose tolerance to NIDDM. The glucose-dependent action of this peptide is an important feature in the treatment of NIDDM as it will protect against hypoglycaemic reactions, the most serious acute side-effect of antidiabetic therapy. Glucose utilization may be enhanced which would improve metabolic control in both NIDDM and IDDM. A glucagon lowering effect will further enhance metabolic control. This article reviews current experiences of the effects of GLP-1 in human studies. It points out the outcomes and limitations of previous trials and discusses future directions for the investigation of its potential use as a new agent in diabetes treatment.
迄今为止，已经收集了大量源自体外实验或动物实验的数据，这些数据支持这样一种观点，即肠道激素胰高血糖素样肽-1（GLP-1）可能作为设计治疗糖尿病新药的模型分子。非胰岛素依赖型糖尿病（NIDDM）患者中GLP-1具有强大的促胰岛素分泌作用这一观察结果支持了这一观点。它增强了β细胞对葡萄糖刺激的胰岛素分泌的敏感性。GLP-1在糖耐量受损的治疗中可能也有作用，在这种情况下β细胞已经对血浆葡萄糖浓度的变化不敏感。正如先前在“糖尿病前期”动物模型中所显示的那样，它可能会延缓糖耐量向NIDDM的逐渐下降。这种肽的葡萄糖依赖性作用是治疗NIDDM的一个重要特征，因为它可以预防低血糖反应，这是抗糖尿病治疗最严重的急性副作用。葡萄糖利用可能会增强，这将改善NIDDM和IDDM的代谢控制。降低胰高血糖素的作用将进一步增强代谢控制。本文综述了GLP-1在人体研究中的当前效应经验。它指出了先前试验的结果和局限性，并讨论了其作为糖尿病治疗新药潜在用途研究的未来方向。
