Xie H, Lautt W W
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Am J Physiol. 1996 May;270(5 Pt 1):E858-63. doi: 10.1152/ajpendo.1996.270.5.E858.
The objective was to determine the site of insulin resistance produced by intraportal atropine or surgical hepatic denervation. A modified euglycemic clamp was used in fasted cats to test the acute effect of insulin (100 mU/kg) on arteriovenous glucose gradients across the hindlimbs (mainly reflecting skeletal muscle), the guts (all organs draining into the portal vein), and the liver. Responses to insulin were determined before and after hepatic denervation and after 3 mg/kg intraportal atropine. The interventions were done in random order. Responses after either intervention were similar and were not potentiated by the combined treatment. Regional insulin resistance was assessed by comparing the change in glucose gradients in response to insulin before and after treatments. Hepatic and gut responses to insulin were unaltered, but hindlimb responses were significantly impaired after denervation or atropine. We speculate that the hepatic parasympathetic nerves regulate release of a liver-generated factor that selectively controls insulin effectiveness in skeletal muscle. This mechanism may be involved with insulin resistance in non-insulin-dependent diabetes and chronic liver disease.
目的是确定门静脉内注射阿托品或手术去肝神经支配所产生的胰岛素抵抗部位。采用改良的正常血糖钳夹技术，对禁食的猫进行试验，以检测胰岛素（100 mU/kg）对后肢（主要反映骨骼肌）、肠道（所有引流至门静脉的器官）和肝脏动静脉葡萄糖梯度的急性影响。在去肝神经支配前后以及静脉注射3 mg/kg阿托品后，测定对胰岛素的反应。干预措施按随机顺序进行。两种干预后的反应相似，联合治疗并未增强反应。通过比较治疗前后对胰岛素反应的葡萄糖梯度变化来评估局部胰岛素抵抗。肝脏和肠道对胰岛素的反应未改变，但去神经支配或注射阿托品后后肢反应显著受损。我们推测，肝副交感神经调节肝脏产生的一种因子的释放，该因子选择性地控制骨骼肌中的胰岛素效能。这种机制可能与非胰岛素依赖型糖尿病和慢性肝病中的胰岛素抵抗有关。
