Direct Administration of Insulin Into Skeletal Muscle Reveals That the Transport of Insulin Across the Capillary Endothelium Limits the Time Course of Insulin to Activate Glucose Disposal
Jenny D. Chiu, Joyce M. Richey, L. Nicole Harrison, Edward Zuniga, Cathryn M. Kolka, Erlinda Kirkman, Martin Ellmerer, and Richard N. Bergman
Department of Physiology and Biophysics, University of Southern California, Keck School of Medicine, Los Angeles, California

OBJECTIVE—Intravenous insulin infusion rapidly increases plasma insulin, yet glucose disposal occurs at a much slower rate. This delay in insulin's action may be related to the protracted time for insulin to traverse the capillary endothelium. An increased delay may be associated with the development of insulin resistance. The purpose of the present study was to investigate whether bypassing the transendothelial insulin transport step and injecting insulin directly into the interstitial space would moderate the delay in glucose uptake observed with intravenous administration of the hormone.

RESEARCH DESIGN AND METHODS—Intramuscular injections of saline (n = 3) or insulin (n = 10) were administered directly into the vastus medialis of anesthetized dogs. Injections of 0.3, 0.5, 0.7, 1.0, and 3.0 units insulin were administered hourly during a basal insulin euglycemic glucose clamp (0.2mU · min–1 · kg–1).

RESULTS—Unlike the saline group, each incremental insulin injection caused interstitial (lymph) insulin to rise within 10 min, indicating rapid diffusion of the hormone within the interstitial matrix. Delay in insulin action was virtually eliminated, indicated by immediate dose-dependent increments in hindlimb glucose uptake. Additionally, bypassing insulin transport by direct injection into muscle revealed a fourfold greater sensitivity to insulin of in vivo muscle tissue than previously reported from intravenous insulin administration.

CONCLUSIONS—Our results indicate that the transport of insulin to skeletal muscle is a rate-limiting step for insulin to activate glucose disposal. Based on these results, we speculate that defects in insulin transport across the endothelial layer of skeletal muscle will contribute to insulin resistance.

直接给与骨骼肌胰岛素揭示胰岛素穿过毛细血管内皮细胞限制胰岛素活化葡萄糖处理的时程
目的:
静脉胰岛素灌注能迅速增加血浆胰岛素量,然而葡萄糖代谢却稍后才开始.这个胰岛素反应滞后的时间可能和胰岛素穿过内皮细胞拖延引起的.滞后时间的增加能够引起胰岛素抵抗.这个研究的目的是通过静脉胰岛素灌注研究到底穿内皮胰岛素运输的旁路和直接将胰岛素注射到骨骼肌的细胞间隙能否调节葡萄糖吸收的滞后.

实验设计和方法:
肌肉注射盐水(3组)和胰岛素(10组)直接注射到麻痹的狗的肌肉中

结果:
每一组增加的胰岛素注射导致细胞间隙(淋巴)胰岛素量在10分钟内升高,标志胰岛素在间隙内扩散速率很高.随胰岛素剂量增加而增加的后肢葡萄糖摄取量表示胰岛素反应的滞后实际上消除了.此外,通过直接将胰岛素注入体外培养骨骼肌组织的胰岛素转运旁路与先前报道的静脉胰岛素灌注的方法相比,前者对胰岛素的敏感性是后者的四倍.

结论:
我们的研究结果表明骨骼肌胰岛素的转运是激活葡萄糖吸收的限速步骤.因此我们推断,机体骨骼肌内皮细胞对胰岛素的转运缺陷会导致胰岛素抵抗.

通过这个摘要，我们可以知道，当我们注射胰岛素后，胰岛素起反应的时间长短可能和胰岛素起效时间和胰岛素抵抗有关

能不能再说的通俗点？

就是说，我们打胰岛素一般都是肌肉注射或者是皮下注射，而这组实验是针对肌肉注射的情况，而胰岛素要启动它的反应，也就是参与葡萄糖的代谢是要从肌肉细胞穿出来进入毛细血管的，毛细血管壁是有内皮细胞组成的，所以胰岛素也要穿过内皮细胞，这就叫胰岛素的转运，胰岛素穿过骨骼肌细胞或内皮细胞的速度越快，那么葡萄糖的吸收也就越快。