Holmäng A, Brzezinska Z, Björntorp P
Wallenberg Laboratory, Sahlgren's Hospital, University of Göteborg, Sweden.
Diabetes. 1993 Jul;42(7):1073-81. doi: 10.2337/diab.42.7.1073.
Statistical studies repeatedly have shown an association between systemic insulin resistance and a preponderance of highly glycolytic, relatively insulin-insensitive muscle fibers as well as a low density of muscle capillaries. The nature of the relationship between these observations is, however, not clear. Female rats were made hyperinsulinemic for 7 days by implantation of osmotic minipumps. Elevated adrenergic activity and secretion of glucocorticoids were controlled by another minipump with propranolol and adrenalectomy was controlled with glucocorticoid substitution. This resulted in hyperinsulinemia and moderate hypoglycemia, the latter probably counteracted by overeating and increased glucagon secretion, as indicated by increased body weight and lower liver glycogen contents, respectively. Systemic insulin sensitivity was increased and measured with a hyperinsulinemic-euglycemic clamp technique. This was paralleled by an elevated glucose utilization estimated as uptake of 2-deoxyglucose in parametrial, retroperitoneal, and inguinal adipose tissues and the soleus and extensor digitorum longus muscles. Glycogen synthesis was also elevated in the soleus muscle. Muscle fiber composition changed with hyperinsulinemia and elevated 2-deoxyglucose uptake toward more fast-twitch, type II, particularly type IIb fibers, whereas the proportion of slow-twitch, type I fibers, diminished. Capillary density was elevated per unit muscle surface area as well as per muscle fiber. This was paralleled by increased insulin sensitivity systemically and in muscles. These results suggest that muscle fiber composition alterations may be a consequence rather than a cause of hyperinsulinemia and that capillarization rather than fiber composition is of importance for insulin sensitivity in muscle.
统计学研究反复表明，全身胰岛素抵抗与大量高糖酵解、相对胰岛素不敏感的肌纤维以及肌肉毛细血管低密度之间存在关联。然而，这些观察结果之间关系的本质尚不清楚。通过植入渗透微型泵使雌性大鼠高胰岛素血症持续7天。另一个装有普萘洛尔的微型泵控制肾上腺素能活性升高和糖皮质激素分泌，通过糖皮质激素替代控制肾上腺切除术。这导致了高胰岛素血症和中度低血糖，后者可能分别通过暴饮暴食和胰高血糖素分泌增加得到抵消，体重增加和肝糖原含量降低表明了这一点。用高胰岛素-正常血糖钳夹技术测量全身胰岛素敏感性增加。这与通过在子宫旁、腹膜后和腹股沟脂肪组织以及比目鱼肌和趾长伸肌中摄取2-脱氧葡萄糖估计的葡萄糖利用率升高相平行。比目鱼肌中的糖原合成也升高。随着高胰岛素血症和2-脱氧葡萄糖摄取增加，肌纤维组成向更多的快肌纤维、II型，特别是IIb型纤维转变，而慢肌纤维、I型纤维的比例减少。单位肌肉表面积以及每条肌纤维的毛细血管密度均升高。这与全身和肌肉中胰岛素敏感性增加相平行。这些结果表明，肌纤维组成改变可能是高胰岛素血症的结果而非原因，并且毛细血管化而非纤维组成对肌肉中的胰岛素敏感性很重要。
