Wu J, Lindström P, Danielsson A, Sehlin J
Department of Histology and Cell Biology, University Hospital, University of Umea, Sweden.
J Hepatol. 1994 Sep;21(3):332-9. doi: 10.1016/s0168-8278(05)80310-1.
Cirrhosis was induced in rats by subcutaneous injections of CCl4 for 13 or 17 weeks. The morphology of the pancreatic islets from the CCl4-treated rats was found to be normal. The CCl4-treated rats had lower fasting serum glucose levels and higher serum insulin levels than the controls. After an oral glucose load (3 g/kg body weight), glucose levels in CCl4-treated rats stayed within the normal range, whereas the serum insulin levels remained higher with a delayed decline of insulin with time. In vitro perifusion of islets from the CCl4-treated rats showed that the response to 16.7 mmol/l glucose was reduced with both lower total insulin output and stimulated insulin output, whereas the patterns of first and second phase of insulin release did not differ. The insulin content of the perifused islets was not affected by 13 weeks of CCl4 treatment. Islets from rats treated with CCl4 for 17 weeks showed normal secretory response to 20 mmol/l L-arginine. Taken together, the results, showing normal or reduced capacity for insulin secretion, suggest that the hyperinsulinemia accompanying CCl4-induced cirrhosis is not due to increased secretion of the pancreatic islets. It may rather be associated with decreased insulin degradation by the liver with cirrhosis.
通过皮下注射四氯化碳13周或17周诱导大鼠肝硬化。发现四氯化碳处理的大鼠胰岛形态正常。与对照组相比，四氯化碳处理的大鼠空腹血清葡萄糖水平较低，血清胰岛素水平较高。口服葡萄糖负荷（3 g/kg体重）后，四氯化碳处理的大鼠血糖水平保持在正常范围内，而血清胰岛素水平仍然较高，且胰岛素随时间延迟下降。对四氯化碳处理的大鼠胰岛进行体外灌流显示，对16.7 mmol/l葡萄糖的反应降低，总胰岛素分泌量和刺激后的胰岛素分泌量均降低，而胰岛素释放的第一相和第二相模式没有差异。灌流胰岛的胰岛素含量不受13周四氯化碳处理的影响。用四氯化碳处理17周的大鼠胰岛对20 mmol/l L-精氨酸显示出正常的分泌反应。综上所述，显示胰岛素分泌能力正常或降低的结果表明，四氯化碳诱导的肝硬化伴发的高胰岛素血症并非由于胰岛分泌增加。它可能与肝硬化时肝脏胰岛素降解减少有关。
