N. T. Jenkins: 115M Ramsey Center, Department of Kinesiology, University of Georgia, 330 River Road, Athens, GA 30602-6554, USA.
Exp Physiol. 2014 Jan;99(1):262-71. doi: 10.1113/expphysiol.2013.074047. Epub 2013 Aug 30.
The vascular actions of insulin are complex, because it can stimulate both nitric oxide-mediated dilatation and endothelin (ET)-1-mediated constriction. We examined vasoreactivity to insulin in isolated feed arteries of the gastrocnemius (GFA) and soleus muscles (SFA) of 32-week-old Long-Evans Tokushima Otsuka (LETO) and Otsuka Long-Evans Tokushima fatty (OLETF) rats, a hyperphagic rodent model of obesity and insulin resistance. The insulin-induced vasoreactivity of SFA and GFA was similar in LETO (healthy) and OLETF (obese/insulin-resistant) rats. However, examination of between-vessel effects revealed a number of novel insights into the heterogeneous vascular effects of insulin. Soleus feed arteries dilated more than GFA in LETO at 100 and 1000 μIU ml(-1) insulin (23 versus 6 and 28 versus 0%, respectively; P < 0.05 for between-vessel differences). Likewise, in OLETF rats there was significantly greater dilatation in SFA than GFA at 10, 100 and 1000 μIU ml(-1) insulin (28 versus 3, 30 versus 0 and 34 versus 0%, respectively; all P < 0.05). In the presence of 3 μm tezosentan, a non-specific endothelin-1 receptor blocker, insulin-induced dilatation of the GFA was enhanced such that differences between vessels were largely abolished in both groups. Furthermore, acetylecholine-induced dilatation was significantly greater in SFA than GFA within each group, whereas sodium nitroprusside-induced dilatory responses were greater in the GFA compared with the SFA. Overall, our findings indicate that the insulin/endothelin-1 vasoconstrictor pathway is more active in GFA than in SFA, independent of obesity in the OLETF rat model.
胰岛素的血管作用较为复杂，因为它既能刺激一氧化氮介导的扩张，又能刺激内皮素（ET）-1介导的收缩。我们检测了 32 周龄长野德岛大耳白兔（LETO）和德岛肥胖糖尿病（OLETF）大鼠腓肠肌（GFA）和比目鱼肌（SFA）孤立供养动脉对胰岛素的血管反应。OLETF 大鼠为肥胖和胰岛素抵抗的杂食性啮齿动物模型。LETO（健康）和 OLETF（肥胖/胰岛素抵抗）大鼠的 SFA 和 GFA 对胰岛素的血管反应相似。然而，对血管间作用的检测揭示了胰岛素对血管的不均匀作用的一些新见解。在 LETO 中，100 和 1000μIU/ml 胰岛素时，比目鱼肌的供养动脉比腓肠肌扩张得更明显（分别为 23%比 6%和 28%比 0%；血管间差异 P < 0.05）。同样，在 OLETF 大鼠中，10、100 和 1000μIU/ml 胰岛素时，比目鱼肌的供养动脉比腓肠肌扩张得更明显（分别为 28%比 3%、30%比 0%和 34%比 0%；所有 P < 0.05）。在 3μm 特索伦坦（非特异性内皮素-1 受体阻滞剂）存在的情况下，GFA 的胰岛素诱导扩张增强，两组之间的血管差异基本消失。此外，乙酰胆碱诱导的扩张在 SFA 中比 GFA 中更明显，而硝普钠诱导的舒张反应在 GFA 中比 SFA 中更明显。总的来说，我们的发现表明，在 OLETF 大鼠模型中，无论肥胖与否，GFA 中的胰岛素/内皮素-1 收缩通路比 SFA 更活跃。
