Hwang D L, Lev-Ran A, Tay Y C, De Meyts P
Department of Diabetes, Endocrinology and Metabolism, City of Hope National Medical Center, Duarte, California.
Horm Metab Res. 1990 Sep;22(9):462-6. doi: 10.1055/s-2007-1004948.
In rats, a moderately hepatotoxic single dose of diethylnitrosamine (DEN) 100 mg/kg causing depletion of liver glycogen, elevation of aspartate aminotransferase and decreased liver uptake of 3-O-methylglucose, resulted in substantial changes in insulin and glucagon balance. Two days after DEN, insulin binding to liver membranes and insulin removal by the liver were sharply reduced whereas its binding to muscle and adipocyte membranes remained unaltered. Serum insulin (random and after an overnight fast) remained normal. Intravenous (I.V.) insulin (10 U/kg) caused the usual degree of hypoglycemia that, however, lasted longer than in the control animals. Removal of glucagon by liver was also depressed in spite of its normal binding to hepatocytes, and peripheral serum glucagon was increased three-fold. I.V. glucagon (40 micrograms/kg) resulted in a blunted response of plasma glucose. I.V. glucose tolerance test (1 g/kg) remained normal in spite of the insulin increase to a level twice as high as in the controls, and in spite of nonsuppressed glucagon. These changes were still present after 1-3 months, but disappeared by 6 months. The results demonstrate remarkable ability of homeostatic mechanisms to preserve normal plasma glucose and glucose tolerance in spite of dramatic changes in insulin and glucagon.
在大鼠中，单剂量100毫克/千克的二乙基亚硝胺（DEN）具有中度肝毒性，可导致肝糖原耗竭、天冬氨酸转氨酶升高以及肝脏对3 - O - 甲基葡萄糖摄取减少，进而使胰岛素和胰高血糖素平衡发生显著变化。给予DEN两天后，胰岛素与肝细胞膜的结合以及肝脏对胰岛素的清除率急剧降低，而其与肌肉和脂肪细胞膜的结合保持不变。血清胰岛素（随机及过夜禁食后）仍保持正常。静脉注射（I.V.）胰岛素（10单位/千克）会引发通常程度的低血糖，但持续时间比对照动物更长。尽管胰高血糖素与肝细胞的结合正常，但其被肝脏清除的过程也受到抑制，外周血清胰高血糖素增加了三倍。静脉注射胰高血糖素（40微克/千克）导致血浆葡萄糖反应减弱。静脉注射葡萄糖耐量试验（1克/千克）尽管胰岛素水平升高至对照动物的两倍，且胰高血糖素未被抑制，但仍保持正常。这些变化在1 - 3个月后仍然存在，但在6个月时消失。结果表明，尽管胰岛素和胰高血糖素发生了显著变化，但体内稳态机制仍具有显著能力维持正常的血浆葡萄糖水平和葡萄糖耐量。
