Halberstam M, Cohen N, Shlimovich P, Rossetti L, Shamoon H
Department of Medicine, Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Diabetes. 1996 May;45(5):659-66. doi: 10.2337/diab.45.5.659.
We compared the effects of oral vanadyl sulfate (100 mg/day) in moderately obese NIDDM and nondiabetic subjects. Three-hour euglycemic-hyperinsulinemic (insulin infusion 30 mU / m / min) clamps were performed after 2 weeks of placebo and 3 weeks of vanadyl sulfate treatment in six nondiabetic control subjects (age 37 +/- 3 years; BMI 29.5 +/- 2.4 kg/m2 ) and seven NIDDM subjects (age 53 +/- 2 years; BMI 28.7 +/-1.8 kg/m2). Glucose turnover ([3-3 H]glucose), glycolysis from plasma glucose, glycogen synthesis, and whole-body carbohydrate and lipid oxidation were evaluated. Decreases in fasting plasma glucose (by approximately 1.7 mmol/l) and HbAlc (both P < 0.05) were observed in NIDDM subjects during treatment; plasma glucose was unchanged in control subjects. In the latter, the glucose infusion rate (GIR) required to maintain euglycemia (40.1 +/- 5.7 and 38.1 +/- 4.8 micromol / kg fat-free mass FFM / min) and glucose disposal (Rd) (41.7 +/- 5.7 and 38.9 +/-4.7 micromol / kg FFM / min were similar during placebo and vanadyl sulfate administration, respectively. Hepatic glucose output (HGO) was completely suppressed in both studies. In contrast, in NIDDM subjects, vanadyl sulfate increased GIR approximately 82% (17.3 +/- 4.7 to 30.9 +/- 2.7 micromol / kg FFM / min, P < 0.05); this improvement in insulin sensitivity was due to both augmented stimulation of Rd (26.0 +/-4.0 vs. 33.6 +/- 2.22 micromol / kg FFM / min, P < 0.05) and enhanced suppression of HGO (7.7 +/- 3.1 vs. 1.3 +/- 0.9 micromol / kg FFM / min, P < 0.05). Increased insulin-stimulated glycogen synthesis accounted for >80% of the increased Rd with vanadyl sulfate (P < 0.005), but plasma glucose flux via glycolysis was unchanged. In NIDDM subjects, vanadyl sulfate was also associated with greater suppression of plasma free fatty acids (FFAs) (P < 0.01) and lipid oxidation (P < 0.05) during clamps. The reduction in HGO and increase in Rd were both highly correlated with the decline in plasma FFA concentrations during the clamp period (P < 0.001). In conclusion, small oral doses of vanadyl sulfate do not alter insulin sensitivity in nondiabetic subjects, but it does improve both hepatic and skeletal muscle insulin sensitivity in NIDDM subjects in part by enhancing insulin's inhibitory effect on lipolysis. These data suggest that vanadyl sulfate may improve a defect in insulin signaling specific to NIDDM.
我们比较了口服硫酸氧钒（100毫克/天）对中度肥胖的非胰岛素依赖型糖尿病（NIDDM）患者和非糖尿病患者的影响。在6名非糖尿病对照受试者（年龄37±3岁；体重指数29.5±2.4千克/平方米）和7名NIDDM受试者（年龄53±2岁；体重指数28.7±1.8千克/平方米）中，先进行2周的安慰剂治疗，然后进行3周的硫酸氧钒治疗，之后进行3小时的正常血糖-高胰岛素血症（胰岛素输注速率为30微单位/平方米/分钟）钳夹试验。评估了葡萄糖周转率（[3-³H]葡萄糖）、血浆葡萄糖的糖酵解、糖原合成以及全身碳水化合物和脂质氧化情况。治疗期间，NIDDM受试者的空腹血糖（降低约1.7毫摩尔/升）和糖化血红蛋白（两者P<0.05）均下降；对照受试者的血浆葡萄糖未发生变化。对于后者，在安慰剂和硫酸氧钒给药期间，维持正常血糖所需的葡萄糖输注速率（GIR）（分别为40.1±5.7和38.1±4.8微摩尔/千克去脂体重/分钟）和葡萄糖处置率（Rd）（分别为41.7±5.7和38.9±4.7微摩尔/千克去脂体重/分钟）相似。在两项研究中，肝葡萄糖输出（HGO）均被完全抑制。相比之下，在NIDDM受试者中，硫酸氧钒使GIR增加了约82%（从17.3±4.7增至30.9±2.7微摩尔/千克去脂体重/分钟，P<0.05）；胰岛素敏感性的这种改善归因于Rd刺激增强（从26.0±4.0增至33.6±2.22微摩尔/千克去脂体重/分钟，P<0.05）以及HGO抑制增强（从7.7±3.1降至1.3±0.9微摩尔/千克去脂体重/分钟，P<0.05）。硫酸氧钒使胰岛素刺激的糖原合成增加，占Rd增加量的80%以上（P<0.005），但通过糖酵解的血浆葡萄糖通量未发生变化。在NIDDM受试者中，硫酸氧钒还与钳夹期间血浆游离脂肪酸（FFA）的更大抑制（P<0.01）和脂质氧化抑制（P<0.05）相关。HGO的降低和Rd的增加均与钳夹期间血浆FFA浓度的下降高度相关（P<0.001）。总之，小剂量口服硫酸氧钒不会改变非糖尿病受试者的胰岛素敏感性，但它确实能改善NIDDM受试者的肝脏和骨骼肌胰岛素敏感性，部分原因是增强了胰岛素对脂肪分解的抑制作用。这些数据表明，硫酸氧钒可能改善NIDDM特有的胰岛素信号缺陷。
