Holst Jens Juul
Department of Medical Physiology, University of Copenhagen, The Panum Institute, Copenhagen N, Denmark.
Diabetes Metab Res Rev. 2002 Nov-Dec;18(6):430-41. doi: 10.1002/dmrr.328.
GLP-1 is a peptide hormone from the intestinal mucosa. It is secreted in response to meal ingestion and normally functions in the so-called ileal brake, that is, inhibition of upper gastrointestinal motility and secretion when nutrients are present in the distal small intestine. It also induces satiety and promotes tissue deposition of ingested glucose by stimulating insulin secretion. Thus, it is an essential incretin hormone. In addition, the hormone has been demonstrated to promote insulin biosynthesis and insulin gene expression and to have trophic effects on the beta cells. The trophic effects include proliferation of existing beta cells, maturation of new cells from duct progenitor cells and inhibition of apoptosis. Furthermore, glucagon secretion is inhibited. Because of these effects, the hormone effectively improves metabolism in patients with type 2 diabetes mellitus. Thus, continuous subcutaneous administration of the peptide for six weeks in patients with rather advanced disease greatly improved glucose profiles and lowered body weight, haemoglobin A(1C), and free fatty acids (FFA). In addition, insulin sensitivity doubled and insulin responses to glucose were greatly improved. There were no side effects. Continuous administration is necessary because of rapid degradation by the enzyme dipeptidyl peptidase-IV. Alternative approaches include the use of analogues that are resistant to the actions of the enzyme, as well as inhibitors of the enzyme. Both approaches have shown remarkable efficacy in both experimental and clinical studies. The GLP-1-based therapy of type 2 diabetes, therefore, represents a new and attractive alternative.
胰高血糖素样肽-1（GLP-1）是一种来自肠黏膜的肽类激素。它在进食后分泌，通常在所谓的回肠制动中发挥作用，即当远端小肠存在营养物质时，抑制上消化道的蠕动和分泌。它还能诱导饱腹感，并通过刺激胰岛素分泌促进摄入葡萄糖的组织沉积。因此，它是一种重要的肠促胰岛素激素。此外，该激素已被证明能促进胰岛素生物合成和胰岛素基因表达，并对β细胞具有营养作用。这些营养作用包括现有β细胞的增殖、导管祖细胞产生新细胞的成熟以及细胞凋亡的抑制。此外，胰高血糖素分泌受到抑制。由于这些作用，该激素能有效改善2型糖尿病患者的代谢。因此，在病情较为严重的患者中连续皮下注射该肽六周，可显著改善血糖水平，降低体重、糖化血红蛋白A1C和游离脂肪酸（FFA）。此外，胰岛素敏感性翻倍，胰岛素对葡萄糖的反应也大大改善。且无副作用。由于该肽会被二肽基肽酶-IV迅速降解，因此需要持续给药。替代方法包括使用对该酶作用具有抗性的类似物以及该酶的抑制剂。这两种方法在实验和临床研究中均显示出显著疗效。因此，基于GLP-1的2型糖尿病治疗代表了一种新且有吸引力的选择。
