Effect of palmitate on carbohydrate utilization and Na/K-ATPase activity in aortic vascular smooth muscle from diabetic rats.
Effect of palmitate on carbohydrate utilization and Na/K-ATPase activity in aortic vascular smooth muscle from diabetic rats.
复制标题
棕榈酸酯对糖尿病大鼠主动脉血管平滑肌碳水化合物利用和 Na/K-ATP 酶活性的影响。
DOI：
10.1023/a:1006961005422
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发表时间：
1999
影响因子：
4.3
通讯作者：
Broderick,TL
中科院分区：
文献类型：
--
作者：
Smith,JM;Solar,SM;Paulson,DJ;Hill,NM;Broderick,TL
一些研究人员报道，糖尿病(DB)大鼠的血管中碳水化合物代谢受到抑制。然而，目前尚不清楚伴随着胰岛素缺乏而导致的长链脂肪酸氧化的交互增加的代谢物是否会加剧DB血管中这一途径的抑制。这种抑制可能会对血管平滑肌产生特别有害的后果，因为有氧糖酵解被认为优先为肌膜Na/K-ATPase提供能量。因此，本研究评估了生理浓度(0.4 mM)和升高浓度(1.2 mM)长链脂肪酸棕榈酸酯对胰岛素缺乏性糖尿病大鼠主动脉碳水化合物利用率和Na/K-ATPase活性的影响。取胸主动脉10周后静脉注射链脲佐菌素60 mg/kg。对照组(C)大鼠和主动脉内膜-中层标本在无棕榈酸酯或存在棕榈酸酯的情况下孵育。糖酵解(μM/g干质量/h)和葡萄糖氧化(μM/g干质量/h)分别用~3H-葡萄糖和~(14)C-葡萄糖定量。在没有和存在2 mM哇巴因的情况下，Na/K-ATPase活性通过测量86 Rb的摄取量来评估。在没有外源性棕榈酸酯的情况下，DB大鼠的主动脉糖酵解(p<；0.05)、葡萄糖氧化(p<；0.01)和估计的外源性葡萄糖产生的ATP减少。然而，尽管糖酵解率降低，但DB和C动脉的Na/K ATPase活性相似。棕榈酸酯(0.4 mM)对DB和C的Na/K-ATPase活性和葡萄糖氧化的抑制程度相似，但对糖酵解均无影响。棕榈酸酯浓度增加到1.2 mM时，对DB或C动脉的葡萄糖氧化、Na/K-ATPase活性或糖酵解没有额外的抑制作用。外源性棕榈酸酯的代谢使DB的ATP产量恢复到控制值。这些数据表明，尽管DB组织的糖酵解和葡萄糖氧化减少，但在没有或存在外源性长链脂肪酸的情况下，C和DB的主动脉Na/K ATPase活性是相似的。因此，糖尿病血管平滑肌中棕榈酸酯的加速氧化对糖酵解或Na/K-ATPase活性没有额外的抑制作用。这些数据表明，胰岛素缺乏的DB大鼠发生的底物利用模式的改变不会损害血管平滑肌的Na/K ATPase活性。
Several investigators have reported that carbohydrate metabolism is suppressed in blood vessels from diabetic (Db) rats. However, it is not known if metabolites from the reciprocal increase in oxidation of long-chain fatty acids that accompanies insulin-deficiency exacerbates the suppression of this pathway in the Db blood vessels. Such inhibition may have particularly deleterious consequences in vascular smooth muscle since aerobic glycolysis is believed to preferentially fuel the sarcolemmal Na/K ATPase in this tissue. Therefore, this study evaluated the effect of physiological (0.4 mM) and elevated (1.2 mM) concentrations of the long-chain fatty acid palmitate on both carbohydrate utilization and Na/K-ATPase activity in aorta from insulin-deficient Db rat. Thoracic aorta were removed from 10 week Db (streptozotocin 60 mg/Kg , i.v.) or control (C) rats and intima-media aortic preparations were incubated in the absence or presence of palmitate. Glycolysis (μM/g dry wt/h) and glucose oxidation (μM/g dry wt/h) were quantified using 3H-glucose and 14C-glucose, respectively. Na/K-ATPase activity was estimated by the measurement of 86rubidium uptake in the absence and presence of 2 mM ouabain.In the absence of exogenous palmitate, glycolysis (p < 0.05), glucose oxidation (p < 0.01) and the estimated ATP production from exogenous glucose were decreased in aorta from Db rat. However, despite this diminished rate of glycolysis, Na/K ATPase activity was similar in Db and C aorta. Palmitate (0.4 mM) inhibited Na/K ATPase activity and glucose oxidation to a similar extent in both Db and C but had no effect on glycolysis in either group. Elevation of palmitate to 1.2 mM had no additional inhibitory effect on glucose oxidation, Na/K ATPase activity or glycolysis in either the Db or C aorta. The metabolism of exogenous palmitate restored the ATP production in Db to control values.These data demonstrate that, despite the diminished glycolysis and glucose oxidation demonstrated in the Db tissue, Na/K ATPase activity was comparable in the C and Db aorta, in the absence or presence of exogenous long-chain fatty acid. Therefore, the accelerated oxidation of palmitate in diabetic vascular smooth muscle had no additional inhibitory effect on glycolysis or Na/K ATPase activity. These data suggest that Na/K ATPase activity in vascular smooth muscle is not impaired by the altered pattern of substrate utilization that occurs in insulin-deficient Db rats.