Wallberg-Henriksson H, Zetan N, Henriksson J
J Biol Chem. 1987 Jun 5;262(16):7665-71.
The mechanisms by which insulin deficiency affects muscle glucose transport were investigated. Epitrochlearis muscles from rats with streptozotocin-induced diabetes and from controls were incubated in vitro for 0.5-14 h. The incubation was shown not to impair muscle energy stores or tissue oxygenation. Diabetes decreased basal 3-O-methylglucose transport by 40% (p less than 0.01), and insulin-stimulated (20 milli-units/ml) glucose transport capacity by 70% (p less than 0.001). In vitro incubation gradually normalized insulin responsiveness (3.77 +/- 0.38 before versus 8.97 +/- 0.65 mumol X ml-1 X h-1 after 12 h of incubation). Basal glucose transport remained significantly reduced. The reversal of the insulin responsiveness did not require the presence of rat serum and, furthermore, took place even in the absence of insulin. In fact, insulin responsiveness was higher after incubation (14 h) with no insulin than with 100 microunits/ml insulin (9.85 +/- 0.59 versus 8.06 +/- 0.59 mumol X ml-1 X h-1, p less than 0.05). Glucose at 30 mM did not affect the normalization of the insulin-stimulated glucose transport capacity, whereas incubation in serum from diabetic rats resulted in a slightly (26%) blunted reversal (7.60 +/- 0.39 versus 8.89 +/- 0.45 mumol X ml-1 X h-1 with diabetic versus control serum for 14 h, p less than 0.05; before incubation the value was 3.87 +/- 0.40). Inhibition of protein synthesis by cycloheximide blocked the normalization by 80%. These results suggest the presence in diabetic serum of some labile factor that might inhibit the glucose transport system. The results indicate that the decreased insulin-stimulated glucose transport capacity, in the insulin-deficient diabetic muscle, is not a direct consequence of the lack of insulin or of high glucose concentrations.
研究了胰岛素缺乏影响肌肉葡萄糖转运的机制。将链脲佐菌素诱导的糖尿病大鼠和对照大鼠的肱三头肌在体外孵育0.5 - 14小时。结果显示孵育不会损害肌肉能量储备或组织氧合。糖尿病使基础3 - O - 甲基葡萄糖转运降低40%（p < 0.01），胰岛素刺激（20毫单位/毫升）的葡萄糖转运能力降低70%（p < 0.001）。体外孵育逐渐使胰岛素反应性恢复正常（孵育12小时前为3.77 ± 0.38，孵育后为8.97 ± 0.65微摩尔·毫升⁻¹·小时⁻¹）。基础葡萄糖转运仍显著降低。胰岛素反应性的恢复不需要大鼠血清的存在，而且即使在没有胰岛素的情况下也会发生。事实上，在无胰岛素的情况下孵育（14小时）后的胰岛素反应性高于在100微单位/毫升胰岛素存在下的反应性（9.85 ± 0.59对8.06 ± 0.59微摩尔·毫升⁻¹·小时⁻¹，p < 0.05）。30 mM的葡萄糖不影响胰岛素刺激的葡萄糖转运能力的恢复正常，而在糖尿病大鼠血清中孵育导致恢复略有减弱（26%）（糖尿病血清孵育14小时后为7.60 ± 0.39，对照血清孵育14小时后为8.89 ± 0.45微摩尔·毫升⁻¹·小时⁻¹，p < 0.05；孵育前的值为3.87 ± 0.40）。用放线菌酮抑制蛋白质合成使恢复过程受阻80%。这些结果表明糖尿病血清中存在某种不稳定因子，可能会抑制葡萄糖转运系统。结果表明，在胰岛素缺乏的糖尿病肌肉中，胰岛素刺激的葡萄糖转运能力下降并非胰岛素缺乏或高血糖浓度的直接后果。
