Holst J J
Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark.
Diabet Med. 1996 Sep;13(9 Suppl 6):S156-60.
Glucagon-like peptide-1 (GLP-1), a product of intestinal expression of the glucagon gene, is a potent insulinotropic hormone released in response to ingestion of meals. Specific GLP-1 receptors, G-protein coupled receptors that activate adenylate cyclase are located in the pancreatic islets and also in brain and various other tissues. GLP-1 also inhibits glucagon secretion and therefore inhibits hepatic glucose production and decreases blood glucose. However, as its effects on insulin secretion are glucose dependent, its effect on blood glucose in self-limiting. Because of these actions GLP-1 administration can completely normalize the hyperglycaemia of NIDDM without a risk of hypoglycaemia and GLP-1 is therefore currently considered as a therapeutic agent. GLP-1 also inhibits gastrointestinal secretion and motility, presumably via interaction with cerebral receptors. This effect may help curtail meal-induced glucose excursions, but may also limit its use. Being a peptide GLP-1 requires parenteral administration, but because of rapid enzymatic degradation its bioavailability is low. Current research efforts are aimed at the development of orally active GLP-1 analogues.
胰高血糖素样肽-1（GLP-1）是胰高血糖素基因在肠道表达的产物，是一种在进食后释放的强效促胰岛素分泌激素。特异性GLP-1受体是激活腺苷酸环化酶的G蛋白偶联受体，位于胰岛以及脑和其他各种组织中。GLP-1还抑制胰高血糖素分泌，因此抑制肝糖生成并降低血糖。然而，由于其对胰岛素分泌的作用依赖于葡萄糖，其对血糖的作用具有自我限制。由于这些作用，给予GLP-1可使非胰岛素依赖型糖尿病（NIDDM）的高血糖完全正常化，而无低血糖风险，因此GLP-1目前被视为一种治疗药物。GLP-1还抑制胃肠分泌和蠕动，推测是通过与脑受体相互作用。这种作用可能有助于减少进餐引起的血糖波动，但也可能限制其应用。作为一种肽，GLP-1需要胃肠外给药，但由于酶促降解迅速，其生物利用度较低。目前的研究工作旨在开发口服活性GLP-1类似物。
