Cleveland Clinic, Division of Endocrinology, Diabetes, & Metabolism, Cleveland, Ohio, USA.
Metab Syndr Relat Disord. 2010 Oct;8(5):459-63. doi: 10.1089/met.2010.0018.
In vitro studies suggest that adiponectin plays an important role in nitric oxide (NO) generation. We studied the relationship between plasma adiponectin and skeletal muscle nitric oxide synthase (NOS) activity in type 2 diabetic (T2DM) patients.
We determined NOS activity in skeletal muscle of 7 T2DM and 8 nondiabetic control subjects under basal conditions and after a 4-h euglycemic insulin (80 mU/m2 x min) clamp.
Insulin-stimulated glucose disposal (Rd) (5.2 +/-0.4 vs. 9.0 +/-0.9 mg/kg-min, P < 0.01) and basal NOS activity (107 +/-45 vs. 459 +/- 100 pmol/min-mg protein, P < 0.05) were reduced in T2DM versus controls. In response to hyperinsulinemia, NOS activity increased approximately two-fold in controls (757 +/- 244, P < 0.05 vs basal) but failed to increase in T2DM (105 +/- 38, P < 0.01 vs. T2DM). Basal NOS protein content was similar in controls and T2DM and did not change following insulin. Plasma adiponectin was decreased in T2DM (4.5 +/- 0.8 vs. 7.0 +/-1.0 microg/mL, P < 0.02) and correlated with insulin-stimulated NOS activity (r = 0.49, P < 0.05) and with Rd (r = 0.50, P < 0.05). In controls and T2DM collectively, Rd correlated with insulin-stimulated NOS activity (r = 0.48, P < 0.05).
Decreased plasma adiponectin correlates with impaired insulin-stimulated NOS activity and severity of insulin resistance in T2DM. Because impaired NO generation plays a central role in endothelial dysfunction and development of atherosclerosis, our results may provide a link between reduced plasma adiponectin levels and accelerated atherosclerosis in T2DM.
体外研究表明脂联素在一氧化氮（NO）生成中发挥重要作用。我们研究了 2 型糖尿病（T2DM）患者血浆脂联素与骨骼肌一氧化氮合酶（NOS）活性之间的关系。
我们在基础状态下和 4 小时的正常血糖胰岛素（80 mU/m2 x min）钳夹后，测定了 7 例 T2DM 患者和 8 例非糖尿病对照者骨骼肌中的 NOS 活性。
与对照组相比，T2DM 患者的胰岛素刺激葡萄糖摄取（Rd）（5.2 +/-0.4 与 9.0 +/-0.9 mg/kg-min，P < 0.01）和基础 NOS 活性（107 +/-45 与 459 +/- 100 pmol/min-mg 蛋白，P < 0.05）均降低。在高胰岛素血症反应中，对照组 NOS 活性增加约两倍（757 +/- 244，P < 0.05 与基础值相比），但 T2DM 患者未能增加（105 +/- 38，P < 0.01 与 T2DM 相比）。对照组和 T2DM 患者的基础 NOS 蛋白含量相似，且胰岛素后无变化。T2DM 患者的血浆脂联素降低（4.5 +/- 0.8 与 7.0 +/-1.0 microg/mL，P < 0.02），并与胰岛素刺激的 NOS 活性（r = 0.49，P < 0.05）和 Rd（r = 0.50，P < 0.05）相关。在对照组和 T2DM 患者中，Rd 与胰岛素刺激的 NOS 活性相关（r = 0.48，P < 0.05）。
血浆脂联素降低与 T2DM 患者胰岛素刺激的 NOS 活性受损和胰岛素抵抗严重程度相关。因为 NO 生成受损在血管内皮功能障碍和动脉粥样硬化发展中起核心作用，我们的结果可能为 T2DM 患者血浆脂联素水平降低与动脉粥样硬化加速之间提供了联系。
