Holmäng A, Jennische E, Björntorp P
Wallenberg Laboratory, Department of Heart and Lung Diseases, Sahlgrenska University Hospital, Göteborg, Sweden.
Diabetologia. 1996 Feb;39(2):206-11. doi: 10.1007/BF00403964.
Research has suggested a role for insulin delivery through capillaries in muscle in the regulation of insulin sensitivity. Therefore, the formation and turn-over of capillary endothelial cells in muscle were studied in relation to exposure to moderately elevated insulin concentrations with or without concomitant increase of corticosterone concentrations. Female rats were exposed to a moderate, physiological hyperinsulinaemia (approximately 450 pmol/l) for 24 h 48 h, 3 days, 7 days and 7 weeks. Propranolol was used to inhibit elevated adrenergic activity. In one insulin-exposed group, corticosterone secretion was controlled by adrenalectomy with substitution of corticosterone to maintain normal concentrations, while another group was left with adrenal corticosterone secretion intact. Rats were exposed to insulin with controlled, non-elevated corticosterone concentrations after adrenalectomy and corticosterone substitution; compared to controls, the number of mitoses in capillary endothelial cells in the soleus and extensor digitorum longus muscle were approximately doubled after 24 h, reaching a maximum, about fivefold higher than controls, after 3 days. After 7 weeks of insulin exposure there were no longer any significant differences between control and insulin-exposed rats. The number of capillaries per unit muscle surface area was moderately (10-15%) but significantly increased at 7 days (only the extensor digitorum longus muscle) and 7 weeks (the extensor digitorum longus and the soleus muscles). In rats exposed to insulin, with intact adrenals, endogenous corticosterone production resulted in concentrations about threefold higher than in rats adrenalectomized with subsequent corticosterone substitution. In these rats the increase in mitoses in capillary endothelium was totally abolished. The results of this study suggest that exposure to insulin in this rat model is followed by a dramatic short-term increase in the formation of new capillary endothelial cells in muscle. It is also suggested that this growth factor-like effect of insulin is abolished by corticosterone. It is suggested that insulin and corticosterone exert opposite effects on the capillary network in muscles, which might be important for the insulin supply to this tissue, and hence for regulation of insulin sensitivity.
研究表明，胰岛素通过肌肉中的毛细血管输送在胰岛素敏感性调节中发挥作用。因此，研究了肌肉中毛细血管内皮细胞的形成和更新与暴露于适度升高的胰岛素浓度（伴或不伴有皮质酮浓度升高）之间的关系。将雌性大鼠暴露于中度生理性高胰岛素血症（约450 pmol/l）中24小时、48小时、3天、7天和7周。使用普萘洛尔抑制升高的肾上腺素能活性。在一个胰岛素暴露组中，通过肾上腺切除术控制皮质酮分泌，并补充皮质酮以维持正常浓度，而另一组则保持肾上腺皮质酮分泌完整。大鼠在肾上腺切除和皮质酮替代后暴露于胰岛素且皮质酮浓度未升高的情况下；与对照组相比，比目鱼肌和趾长伸肌中毛细血管内皮细胞的有丝分裂数在24小时后约增加一倍，在3天后达到最大值，比对照组高约五倍。胰岛素暴露7周后，对照组和胰岛素暴露组大鼠之间不再有任何显著差异。每单位肌肉表面积的毛细血管数量在7天（仅趾长伸肌）和7周（趾长伸肌和比目鱼肌）时适度增加（10 - 15%）但显著增加。在肾上腺完整的胰岛素暴露大鼠中，内源性皮质酮产生导致的浓度比肾上腺切除后补充皮质酮的大鼠高约三倍。在这些大鼠中，毛细血管内皮中有丝分裂的增加完全被消除。本研究结果表明，在该大鼠模型中暴露于胰岛素后，肌肉中新毛细血管内皮细胞的形成会在短期内急剧增加。还表明胰岛素的这种生长因子样作用被皮质酮消除。提示胰岛素和皮质酮对肌肉中的毛细血管网络发挥相反作用，这可能对该组织的胰岛素供应很重要，因此对胰岛素敏感性的调节也很重要。
