Wardzala L J, Hirshman M, Pofcher E, Horton E D, Mead P M, Cushman S W, Horton E S
J Clin Invest. 1985 Aug;76(2):460-9. doi: 10.1172/JCI111994.
The effects of chronic insulin administration on the metabolism of isolated adipose cells and muscle were studied. Adipose cells from 2 and 6 wk insulin-treated and control rats, fed either chow or chow plus sucrose, were prepared, and insulin binding, 3-O-methylglucose transport, glucose metabolism, and lipolysis were measured at various insulin concentrations. After 2 wk of treatment, adipose cell size and basal glucose transport and metabolism were unaltered, but insulin-stimulated transport and glucose metabolism were increased two- to threefold when cells were incubated in either 0.1 mM glucose (transport rate limiting) or 10 mM glucose (maximum glucose metabolism). Insulin binding was increased by 30%, but no shift in the insulin dose-response curve for transport or metabolism occurred. After 6 wk of treatment, the effects of hyperinsulinemia on insulin binding and glucose metabolism persisted and were superimposed on the changes in cell function that occurred with increasing cell size in aging rats. Hyperinsulinemia for 2 or 6 wk did not alter basal or epinephrine-stimulated lipolysis in adipose cells or the antilipolytic effect of insulin. In incubated soleus muscle strips, insulin-stimulated glucose metabolism was significantly increased after 2 wk of hyperinsulinemia, but these increases were not observed after 6 wk of treatment. We conclude that 2 wk of continuous hyperinsulinemia results in increased insulin-stimulated glucose metabolism in both adipose cells and soleus muscle. Despite increased insulin binding to adipose cells, no changes in insulin sensitivity were observed in adipose cells or muscle. In adipose cells, the increased glucose utilization resulted from both increased transport (2 wk only) and intracellular glucose metabolism (2 and 6 wk). In muscle, after 2 wk of treatment, both glycogen synthesis and total glucose metabolism were increased. These effects of hyperinsulinemia were lost in muscle after 6 wk of treatment, when compared with sucrose-supplemented controls.
研究了长期注射胰岛素对分离的脂肪细胞和肌肉代谢的影响。制备了来自2周和6周接受胰岛素治疗及对照大鼠的脂肪细胞，这些大鼠分别喂食普通饲料或普通饲料加蔗糖，然后在不同胰岛素浓度下测量胰岛素结合、3 - O - 甲基葡萄糖转运、葡萄糖代谢和脂肪分解。治疗2周后，脂肪细胞大小、基础葡萄糖转运和代谢未改变，但当细胞在0.1 mM葡萄糖（转运速率限制）或10 mM葡萄糖（最大葡萄糖代谢）中孵育时，胰岛素刺激的转运和葡萄糖代谢增加了两到三倍。胰岛素结合增加了30%，但转运或代谢的胰岛素剂量 - 反应曲线未发生偏移。治疗6周后，高胰岛素血症对胰岛素结合和葡萄糖代谢的影响持续存在，并叠加在衰老大鼠中随着细胞大小增加而发生的细胞功能变化上。2周或6周的高胰岛素血症均未改变脂肪细胞中的基础或肾上腺素刺激的脂肪分解，也未改变胰岛素的抗脂解作用。在孵育的比目鱼肌条中，高胰岛素血症2周后胰岛素刺激的葡萄糖代谢显著增加，但治疗6周后未观察到这些增加。我们得出结论，连续2周的高胰岛素血症导致脂肪细胞和比目鱼肌中胰岛素刺激的葡萄糖代谢增加。尽管胰岛素与脂肪细胞的结合增加，但在脂肪细胞或肌肉中未观察到胰岛素敏感性的变化。在脂肪细胞中，葡萄糖利用增加是由于转运增加（仅2周）和细胞内葡萄糖代谢增加（2周和6周）。在肌肉中，治疗2周后，糖原合成和总葡萄糖代谢均增加。与补充蔗糖的对照组相比，治疗6周后肌肉中高胰岛素血症的这些作用消失。
