Napoli R, Davalli A M, Hirshman M F, Weitgasser R, Weir G C, Horton E S
Research Division, Joslin Diabetes Center, Boston, Massachusetts 02215, USA.
J Clin Invest. 1996 Mar 15;97(6):1389-97. doi: 10.1172/JCI118559.
Chronic insulin therapy improves but does not restore impaired insulin-mediated muscle glucose uptake in human diabetes or muscle glucose uptake, transport, and transporter translocation in streptozocin diabetic rats. To determine whether this inability is due to inadequate insulin replacement, we studied fasted streptozocin-induced diabetic Lewis rats either untreated or after islet transplantation under the kidney capsule. Plasma glucose was increased in untreated diabetics and normalized by the islet transplantation (110 +/- 5, 452 +/- 9, and 102 +/- 3 mg/dl in controls, untreated diabetics, and transplanted diabetics, respectively). Plasma membrane and intracellular microsomal membrane vesicles were prepared from hindlimb skeletal muscle of basal and maximally insulin-stimulated rats. Islet transplantation normalized plasma membrane carrier-mediated glucose transport Vmax, plasma membrane glucose transporter content, and insulin-induced transporter translocation. There were no differences in transporter intrinsic activity (Vmax/Ro) among the three groups. Microsomal membrane GLUT4 content was reduced by 30% in untreated diabetic rats and normal in transplanted diabetics, whereas the insulin-induced changes in microsomal membrane GLUT4 content were quantitatively similar in the three groups. There were no differences in plasma membrane GLUT1 among the groups and between basal and insulin stimulated states. Microsomal membrane GLUT1 content was increased 60% in untreated diabetics and normalized by the transplantation. In conclusion, an adequate insulin delivery in the peripheral circulation, obtained by islet transplantation, fully restores the muscle glucose transport system to normal in streptozocin diabetic rats.
长期胰岛素治疗可改善但不能恢复人类糖尿病患者受损的胰岛素介导的肌肉葡萄糖摄取，或链脲佐菌素诱导的糖尿病大鼠的肌肉葡萄糖摄取、转运及转运体易位。为确定这种无能是否归因于胰岛素替代不足，我们研究了禁食的链脲佐菌素诱导的糖尿病Lewis大鼠，一组未治疗，另一组在肾被膜下进行胰岛移植。未治疗的糖尿病大鼠血浆葡萄糖升高，胰岛移植后恢复正常（对照组、未治疗的糖尿病大鼠和移植后的糖尿病大鼠的血浆葡萄糖分别为110±5、452±9和102±3mg/dl）。从基础状态和最大胰岛素刺激状态的大鼠后肢骨骼肌制备质膜和细胞内微粒体膜囊泡。胰岛移植使质膜载体介导的葡萄糖转运Vmax、质膜葡萄糖转运体含量及胰岛素诱导的转运体易位恢复正常。三组之间转运体内在活性（Vmax/Ro）无差异。未治疗的糖尿病大鼠微粒体膜GLUT4含量降低30%，移植后的糖尿病大鼠正常，而三组中胰岛素诱导的微粒体膜GLUT4含量变化在数量上相似。各组之间以及基础状态和胰岛素刺激状态之间质膜GLUT1无差异。未治疗的糖尿病大鼠微粒体膜GLUT1含量增加60%，移植后恢复正常。总之，通过胰岛移植在周围循环中实现充足的胰岛素递送，可使链脲佐菌素诱导的糖尿病大鼠的肌肉葡萄糖转运系统完全恢复正常。
