Biomedical Research Group, Department of Science, Institute of Technology Tallaght Dublin, Ireland.
Metabolism. 2012 Nov;61(11):1528-37. doi: 10.1016/j.metabol.2012.05.003. Epub 2012 Jun 7.
Nitric oxide (NO·) exerts key regulatory functions including vasodilation and glucose uptake. Thus reduced NO· levels are associated with insulin resistance and hypertension. In this preliminary work we aimed to measure the levels of NO· metabolites in serum and skeletal muscle of obese and non-obese subjects, with or without type 2 diabetes mellitus (T2DM).
Fifteen sedentary male participants [7 obese controls (C) vs 5 obese and 3 non-obese T2DM; age 54±9 years] were selected according to their BMI (>30 kg/m(2) for obese and 23-27 kg/m(2) for non-obese participants) and evaluated for fasted values of blood glucose, HbA1c, lipid profile, serum CRP (C-reactive protein), erythrocyte glutathione (GSH) metabolism, plasma adiponectin, leptin and cytokines (TNF-α and INFγ), serum and skeletal muscle nitric oxide metabolites (nitrite and nitrates; tNOx) and skeletal muscle nNOS and iNOS expression. Body composition was measured by whole body DEXA and muscle microbiopsy was performed in the vastus lateralis.
We found that serum tNOx (total nitrite/nitrate; μmol/L) was lower in obese T2DM group (12.7±3.5) when compared with their controls (21.1±2.4), although the non-obese group presented higher concentration of tNOx (33.8±7.2). Skeletal muscle nNOS was higher in obese controls, lower in non-obese T2DM and undetected in obese T2DM. On the other hand, expression of iNOS had an inverse relationship with nNOS, showing higher expression in obese T2DM, decrease in non-obese T2DM and absence in obese control group. tNOx levels (μmol/mg protein) were decreased in the non-obese T2DM group (12.07±0.59) when compared with the obese control (21.68±6.2) and the obese T2DM group (26.3±7.26).
We conclude that the decreased serum NO∙ production in obese T2DM patients seems to be associated with adipose mass as lower adiposity was associated with normal NO∙ which was reduced in the skeletal muscle of the non-obese T2DM patients. We suggest that the lower adiposity (and higher adiponectin) in non-obese T2DM could be responsible for differential levels of NO∙ production and insulin resistance.
一氧化氮（NO·）具有关键的调节功能，包括血管舒张和葡萄糖摄取。因此，NO·水平降低与胰岛素抵抗和高血压有关。在这项初步研究中，我们旨在测量肥胖和非肥胖受试者（有或没有 2 型糖尿病（T2DM））血清和骨骼肌中 NO·代谢物的水平。
根据 BMI（肥胖者>30 kg/m²，非肥胖者 23-27 kg/m²）选择 15 名久坐的男性参与者[7 名肥胖对照者（C）与 5 名肥胖和 3 名非肥胖 T2DM 患者；年龄 54±9 岁]，并评估空腹血糖、HbA1c、血脂谱、血清 CRP（C 反应蛋白）、红细胞谷胱甘肽（GSH）代谢、血浆脂联素、瘦素和细胞因子（TNF-α和 INFγ）、血清和骨骼肌一氧化氮代谢物（亚硝酸盐和硝酸盐；tNOx）和骨骼肌 nNOS 和 iNOS 表达。全身 DEXA 测量身体成分，股外侧肌进行肌肉活检。
我们发现，与肥胖对照组相比（21.1±2.4μmol/L），肥胖 T2DM 组的血清 tNOx（总亚硝酸盐/硝酸盐；μmol/L）较低，而非肥胖组的 tNOx 浓度较高（33.8±7.2μmol/L）。肥胖对照组的 nNOS 较高，非肥胖 T2DM 组较低，肥胖 T2DM 组未检测到。另一方面，iNOS 的表达与 nNOS 呈反比，肥胖 T2DM 组表达较高，非肥胖 T2DM 组表达降低，肥胖对照组无表达。与肥胖对照组（21.68±6.2μmol/mg 蛋白）和肥胖 T2DM 组（26.3±7.26μmol/mg 蛋白）相比，非肥胖 T2DM 组（12.07±0.59μmol/mg 蛋白）的 tNOx 水平降低。
我们得出结论，肥胖 T2DM 患者血清中 NO·产生减少似乎与脂肪量有关，因为较低的体脂与正常的 NO·有关，而骨骼肌中 NO·在非肥胖 T2DM 患者中减少。我们认为，非肥胖 T2DM 中较低的体脂（和较高的脂联素）可能是导致不同水平的 NO·产生和胰岛素抵抗的原因。
