Pénicaud L, Rohner-Jeanrenaud F, Jeanrenaud B
Am J Physiol. 1986 Jun;250(6 Pt 1):E662-8. doi: 10.1152/ajpendo.1986.250.6.E662.
Ventromedial hypothalamic (VMH)-lesioned rats were tested 1 and 6 wk after the lesions to determine, by euglycemic-hyperinsulinemic clamps, their tissue response to insulin. One week after the lesions, total glucose metabolism was more sensitive and responsive to insulin than in age-matched controls. In the two groups, hepatic glucose production was suppressed at almost identical insulin concentrations (approximately 550 microU/ml). Six weeks after the VMH lesions, the increased insulin responsiveness of total glucose metabolism disappeared and glucose metabolism became less insulin sensitive (right, shifted dose-response curve) than that of control animals. Furthermore, hepatic glucose production of VMH-lesioned rats was now inhibited by 45% at most and at the supraphysiological insulin concentration of 16,000 microU/ml, while it was totally suppressed by 550 microU/ml of the hormone in age-matched controls. This defect was accompanied by a lack of decrease in plasma glucagon levels during the clamps carried out at maximal insulin concentration. In summary, in a first phase after VMH lesion, rats are hypersensitive and hyperresponsive to insulin; and in a later phase, when obesity is well established, VMH-lesioned rats become insulin resistant and are characterized by a decreased in vivo sensitivity and responsiveness of liver and muscles to the hormone.
对下丘脑腹内侧核（VMH）损伤的大鼠在损伤后1周和6周进行测试，通过正常血糖-高胰岛素钳夹试验来确定其组织对胰岛素的反应。损伤后1周，总的葡萄糖代谢比年龄匹配的对照组对胰岛素更敏感且反应更强。在两组中，几乎在相同的胰岛素浓度（约550微单位/毫升）下，肝葡萄糖生成受到抑制。VMH损伤6周后，总的葡萄糖代谢对胰岛素反应性增加的现象消失，且葡萄糖代谢对胰岛素的敏感性低于对照动物（右侧，剂量-反应曲线偏移）。此外，VMH损伤大鼠的肝葡萄糖生成现在最多被抑制45%，且是在超生理胰岛素浓度16000微单位/毫升时，而在年龄匹配的对照组中，550微单位/毫升的该激素就能完全抑制肝葡萄糖生成。在最大胰岛素浓度下进行钳夹试验期间，这种缺陷伴随着血浆胰高血糖素水平缺乏下降。总之，在VMH损伤后的第一阶段，大鼠对胰岛素高度敏感且反应过度；而在后期，当肥胖症充分发展时，VMH损伤的大鼠会出现胰岛素抵抗，其特征是肝脏和肌肉在体内对该激素的敏感性和反应性降低。
