Siegel E G, Seidenstücker A, Gallwitz B, Schmitz F, Reinecke-Lüthge A, Klöppel G, Fölsch U R, Schmidt W E
Laboratory of Molecular Gastroenterology and Hepatology, Gastrointestinal Unit, 1st Department of Medicine, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany.
J Endocrinol. 2000 Jan;164(1):13-9. doi: 10.1677/joe.0.1640013.
Liver cirrhosis is often accompanied by a disturbed carbohydrate metabolism similar to type 2 diabetes. To investigate the severity of the defect in insulin secretion in this form of diabetes, we measured insulin release from isolated pancreatic islets of rats with CCl(4)-phenobarbital-induced liver cirrhosis. Cirrhosis was confirmed by clinical signs, elevated liver enzymes and histology. Fasting venous plasma glucose concentrations were equal in rats with liver cirrhosis and in controls. Plasma insulin and glucagon concentrations were significantly greater (P<0.01) in cirrhotic rats than in control animals. Glucose (16.7 mM)-induced stimulation of insulin release from pancreatic islets revealed a twofold increase in control and cirrhotic rats. Basal and stimulated insulin secretion, however, were significantly lower in cirrhotic animals. The incretin hormone, glucagon-like peptide-1 (GLP-1), has therapeutic potential for the treatment of type 2 diabetes. Therefore, islets from control and cirrhotic animals were incubated with GLP-1 in concentrations from 10(-)(11) to 10(-)(6) M. GLP-1 stimulated insulin release in a concentration-dependent manner. In islets from cirrhotic rats, basal and stimulated insulin secretion was blunted compared with controls. These data show that the hyperinsulinemia observed in liver cirrhosis is not due to an increase of insulin secretion from islets, but could be explained by decreased hepatic clearance of insulin. GLP-1 may ameliorate diabetes in patients with liver cirrhosis.
肝硬化常伴有类似于2型糖尿病的碳水化合物代谢紊乱。为了研究这种糖尿病形式下胰岛素分泌缺陷的严重程度，我们测量了四氯化碳-苯巴比妥诱导的肝硬化大鼠分离胰岛的胰岛素释放情况。通过临床症状、肝酶升高和组织学检查证实了肝硬化。肝硬化大鼠和对照组大鼠的空腹静脉血浆葡萄糖浓度相等。肝硬化大鼠的血浆胰岛素和胰高血糖素浓度显著高于对照动物（P<0.01）。葡萄糖（16.7 mM）诱导的胰岛胰岛素释放刺激在对照大鼠和肝硬化大鼠中均显示出两倍的增加。然而，肝硬化动物的基础胰岛素分泌和刺激后胰岛素分泌均显著降低。肠促胰岛素激素胰高血糖素样肽-1（GLP-1）具有治疗2型糖尿病的潜力。因此，将对照动物和肝硬化动物的胰岛与浓度为10^(-11)至10^(-6) M的GLP-1一起孵育。GLP-1以浓度依赖性方式刺激胰岛素释放。与对照组相比，肝硬化大鼠胰岛的基础胰岛素分泌和刺激后胰岛素分泌均受到抑制。这些数据表明，肝硬化中观察到的高胰岛素血症并非由于胰岛胰岛素分泌增加，而是可以用肝脏胰岛素清除率降低来解释。GLP-1可能改善肝硬化患者的糖尿病。
