Sugiyama Y, Shimura Y, Ikeda H
Central Research Division, Takeda Chemical Industries, Osaka, Japan.
Endocrinol Jpn. 1989 Apr;36(2):245-51. doi: 10.1507/endocrj1954.36.245.
Eight-week-old, female Wistar fatty rats and their lean littermates were given a 30% sucrose solution in addition to a laboratory chow diet and water for 7 weeks. The fatty rats were hyperinsulinemic and hyperlipidemic, but normoglycemic when they drank only water. The hepatic activities of insulin-inducible glucokinase (GK), pyruvate kinase (PK), and malic enzyme (ME) were higher in the fatty rats than in the lean rats, whereas the insulin-suppressible glucose-6-phosphatase (G6Pase) activity was similar in both types of rats, indicating the normal response of hepatic enzymes to hyperinsulinemia in the fatty rats. When they drank the sucrose solution, the fatty rats, but not the lean rats, developed hyperglycemia over 200 mg/dl. Plasma insulin and triglyceride concentrations increased in both types of rats. Although the hepatic activities of GK, PK, and ME in the lean rats, and PK and ME in the fatty rats increased in response to the increase in plasma insulin, GK activity decreased in the fatty rats. On the other hand, G6Pase activity increased in both types of rats. As a result, the G6Pase/GK ratio, which may reflect net glucose handling in the liver, increased twofold in the fatty rats, but did not alter in the lean rats. From these findings, we conclude that sucrose ingestion induces an increase in hepatic glucose production through derangement of the hepatic enzyme profile and that the resultant decrease in hepatic glucose handling may be one of the pathogenic factors participating in the development of hyperglycemia in Wistar fatty rats.
八周龄雌性Wistar肥胖大鼠及其瘦的同窝仔鼠除了给予实验室常规饲料和水外，还给予30%的蔗糖溶液，持续7周。肥胖大鼠有高胰岛素血症和高脂血症，但仅饮水时血糖正常。肥胖大鼠肝脏中胰岛素诱导的葡萄糖激酶（GK）、丙酮酸激酶（PK）和苹果酸酶（ME）的活性高于瘦大鼠，而胰岛素抑制的葡萄糖-6-磷酸酶（G6Pase）活性在两种大鼠中相似，这表明肥胖大鼠肝脏酶对高胰岛素血症有正常反应。当它们饮用蔗糖溶液时，肥胖大鼠出现血糖超过200mg/dl的高血糖症，而瘦大鼠没有。两种大鼠的血浆胰岛素和甘油三酯浓度均升高。尽管瘦大鼠肝脏中GK、PK和ME的活性以及肥胖大鼠肝脏中PK和ME的活性随血浆胰岛素升高而增加，但肥胖大鼠肝脏中GK活性降低。另一方面，两种大鼠肝脏中G6Pase活性均升高。结果，可能反映肝脏葡萄糖净处理的G6Pase/GK比值在肥胖大鼠中增加了两倍，而在瘦大鼠中没有变化。从这些发现中，我们得出结论，摄入蔗糖通过肝脏酶谱紊乱导致肝脏葡萄糖生成增加，并且由此导致的肝脏葡萄糖处理能力下降可能是参与Wistar肥胖大鼠高血糖症发生发展的致病因素之一。
