Schirra Jörg, Göke Burkhard
Department of Internal Medicine II, Marchioninistr. 15, University of Munich, Munich D-81377, Germany.
Regul Pept. 2005 Jun 15;128(2):109-15. doi: 10.1016/j.regpep.2004.06.018.
The proglucagon-derived peptide glucagon-like peptide-1 (GLP-1) is an intestinal signal peptide postprandially released from the L cells of the lower gut. Exogenously administered the synthetic hormone exerts a glucose-dependent insulinotropic effect at the pancreatic beta-cells and lowers plasma glucagon by an inhibitory effect against the alpha-cells. It delays gastric emptying by relaxation of the gastric fundus, inhibition of antral contractility, and stimulation of both the tonic and phasic motility of the pyloric sphincter. Enhancement of insulin, suppression of glucagon, and inhibition of gastric emptying are the main determinants controlling glucose homeostasis with GLP-1. Human studies employing the specific GLP-1 receptor antagonist exendin(9-39) show that endogenously released GLP-1 likewise controls fasting plasma glucagon, stimulates insulin, and influences all the motoric mechanisms known to control gastric emptying. Therefore, GLP-1 is discussed as an incretin hormone and as an enterogastrone in man. Synthetic GLP-1 also suppresses gastric acid and pancreatic enzyme secretion. The inhibitory effects on upper gastrointestinal functions are at least partly mediated by vagal-cholinergic inhibition and may involve interactions with vagal afferent pathways and/or circumventricular regions within the CNS. GLP-1 is a candidate humoral mediator of the 'ileal brake' exerting inhibition of upper gastrointestinal function preventing malabsorption and postprandial metabolic disturbances. As human studies indicate a central action of GLP-1 in reduction of food intake, it is uncertain if this is a consequence of induction of satiety or of transduction of visceral aversive stress signals.
胰高血糖素原衍生肽胰高血糖素样肽-1（GLP-1）是一种餐后从下消化道L细胞释放的肠信号肽。外源性给予这种合成激素可在胰腺β细胞发挥葡萄糖依赖性促胰岛素分泌作用，并通过对α细胞的抑制作用降低血浆胰高血糖素水平。它通过胃底松弛、抑制胃窦收缩力以及刺激幽门括约肌的紧张性和阶段性运动来延迟胃排空。胰岛素增强、胰高血糖素抑制以及胃排空抑制是GLP-1控制葡萄糖稳态的主要决定因素。采用特异性GLP-1受体拮抗剂艾塞那肽（9-39）的人体研究表明，内源性释放的GLP-1同样可控制空腹血浆胰高血糖素水平、刺激胰岛素分泌，并影响所有已知的控制胃排空的运动机制。因此，GLP-1被认为是人体内的一种肠促胰岛素激素和肠抑胃素。合成的GLP-1还可抑制胃酸和胰酶分泌。对上部胃肠道功能的抑制作用至少部分是由迷走神经胆碱能抑制介导的，可能涉及与迷走神经传入途径和/或中枢神经系统内室周区域的相互作用。GLP-1是“回肠制动”的一种潜在体液介质，可抑制上部胃肠道功能，防止吸收不良和餐后代谢紊乱。由于人体研究表明GLP-1在减少食物摄入量方面具有中枢作用，目前尚不确定这是饱腹感诱导的结果还是内脏厌恶应激信号传导的结果。
