Latour Martin G, Lautt W Wayne
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Can J Physiol Pharmacol. 2002 Jan;80(1):8-12. doi: 10.1139/y01-094.
Hepatic insulin sensitizing substance (HISS), a putative hormone released from the liver in response to insulin in fed animals, accounts for 50-60% of insulin action. HISS release is regulated by permissive control of the hepatic parasympathetic nerves. The objectives were to develop the rapid insulin sensitivity test (RIST) in conscious rats, and to assess the effects of anesthesia, atropine, feeding, and fasting on insulin action. The RIST index, expressed as milligrams glucose per kilogram body weight required to maintain euglycemia after a 50 mU/kg bolus of insulin, was similar in conscious and anesthetized rats (238.6+/-42.5 vs. 225.3+/-30.4 mg/kg). Atropine produced a 56% inhibition of insulin action in fed rats. After a 24 h fast, full HISS-dependent insulin resistance had developed as shown by a low RIST index that was not reduced further by atropine. Fasting caused a 10.5% decrease in insulin action per hour over six hours. HISS-dependent insulin resistance in 24-h fasted rats was reversed 4 h after re-feeding (90.9+/-12.3 vs. 204.5+/-30.5 mg/kg). We conclude that HISS-dependent and HISS-independent insulin action, as assessed by the RIST, is similar in conscious and pentobarbital-anesthetized rats. Pharmacological blockade of HISS-dependent insulin action and physiological regulation of HISS action by feeding-fasting is confirmed. Re-feeding fasted rats reversed HISS-dependent insulin resistance. Merits of use of the RIST in conscious versus anesthetized rats are discussed.
肝脏胰岛素增敏物质（HISS）是进食动物肝脏在胰岛素作用下释放的一种假定激素，占胰岛素作用的50%-60%。HISS的释放受肝脏副交感神经的允许性控制。目的是在清醒大鼠中开发快速胰岛素敏感性试验（RIST），并评估麻醉、阿托品、进食和禁食对胰岛素作用的影响。RIST指数以每千克体重维持50 mU/kg胰岛素推注后血糖正常所需的葡萄糖毫克数表示，清醒大鼠和麻醉大鼠相似（238.6±42.5 vs. 225.3±30.4 mg/kg）。阿托品使进食大鼠的胰岛素作用受到56%的抑制。禁食24小时后，出现了完全依赖HISS的胰岛素抵抗，RIST指数较低，且阿托品不再进一步降低该指数。禁食在6小时内使胰岛素作用每小时降低10.5%。重新进食4小时后，24小时禁食大鼠中依赖HISS的胰岛素抵抗得到逆转（90.9±12.3 vs. 204.5±30.5 mg/kg）。我们得出结论，通过RIST评估，清醒大鼠和戊巴比妥麻醉大鼠中依赖HISS和不依赖HISS的胰岛素作用相似。证实了对依赖HISS的胰岛素作用进行药理学阻断以及通过进食-禁食对HISS作用进行生理调节。重新喂食禁食大鼠可逆转依赖HISS的胰岛素抵抗。讨论了在清醒大鼠与麻醉大鼠中使用RIST的优点。
