Kreutner W, Springer S C, Sherwood J E
Am J Physiol. 1975 Feb;228(2):663-71. doi: 10.1152/ajplegacy.1975.228.2.663.
The genetically obese-hyperglycemic mouse, C57 BL/6J-ob, exhibits hyperglycemia and hyperinsulinemia. We have investigated the in vivo hepatic response to a glucose load in female obese mice and their lean littermates. Within 15 min after the administration of glucose (1.5 g/kg) to fasted lean mice, gluconeogenesis from [14C]alanine markedly decreased, endogenous hepatic levels of alanine and other gluconeogenic precursors increased, and glycogen synthetase was activated by virtue of an increase in the precent of synthetase I. These changes persisted up to 60 min and then returned to fasting values. In contrast, obese mice did not produce any of the above changes when given a similar glucose load. Failure to activate glycogen synthetase occurred despite the presence of synthetase D phosphatase activity. In lean mice [14C]glucose synthesis from [14C]glycerol exceeded that from [14C]alanine and was not suppressed by glucose administration, indicating the site of control of gluconeogenesis to be below the triose phosphate step. Insulin resistance in obese mice may involve the liver, as well as peripheral tissues studied by others.
遗传性肥胖高血糖小鼠C57 BL/6J-ob表现出高血糖和高胰岛素血症。我们研究了雌性肥胖小鼠及其瘦的同窝仔鼠对葡萄糖负荷的体内肝脏反应。在给禁食的瘦小鼠注射葡萄糖（1.5 g/kg）后15分钟内，[14C]丙氨酸的糖异生显著减少，肝脏内源性丙氨酸和其他糖异生前体水平升高，并且糖原合成酶因合成酶I百分比的增加而被激活。这些变化持续到60分钟，然后恢复到禁食值。相比之下，肥胖小鼠在给予相似葡萄糖负荷时未产生上述任何变化。尽管存在合成酶D磷酸酶活性，但糖原合成酶未能被激活。在瘦小鼠中，[14C]甘油生成[14C]葡萄糖的量超过了[14C]丙氨酸生成[14C]葡萄糖的量，并且不受葡萄糖注射的抑制，这表明糖异生的控制点在磷酸丙糖步骤以下。肥胖小鼠的胰岛素抵抗可能涉及肝脏以及其他人研究的外周组织。
