Differential modulation of glucose, lactate, and pyruvate oxidation by insulin and dichloroacetate in the rat heart
Differential modulation of glucose, lactate, and pyruvate oxidation by insulin and dichloroacetate in the rat heart
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DOI：
10.1152/ajpheart.01117.2002
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发表时间：
2003-07-01
影响因子：
4.8
通讯作者：
Chatham, JC
中科院分区：
文献类型：
--
作者：
Lloyd, S;Brocks, C;Chatham, JC
尽管乳酸和丙酮酸是体内能量产生的潜在底物，但我们对碳水化合物代谢的控制和调节的理解主要基于葡萄糖是唯一可用碳水化合物的研究。因此，本研究的目的是确定乳酸，丙酮酸和葡萄糖的贡献，能量产生的隔离，灌注大鼠心脏在一系列的胰岛素浓度和丙酮酸脱氢酶与二氯乙酸（DCA）激活后。用生理浓度的[1-C-13]葡萄糖、[1-C-13]乳酸盐、[2-C-13]丙酮酸盐和未标记的棕榈酸盐灌注心脏45 min。将心脏冷冻夹闭，并对组织提取物进行C-13 NMR谷氨酸盐同位素异构体分析。葡萄糖、乳酸盐和丙酮酸盐均对心肌能量产生有显著贡献;然而，在不存在胰岛素的情况下，葡萄糖仅贡献总丙酮酸盐氧化的25-30%。即使在碳水化合物占进入三羧酸（TCA）循环的底物的>95%的条件下，我们发现葡萄糖占总碳水化合物氧化的至多50-60%。尽管丙酮酸的浓度仅为0.1 mM，但它对进入TCA循环的总乙酰辅酶A的贡献率约为10%-30%。我们还发现，胰岛素和DCA不仅增加葡萄糖氧化，而且还增加外源性丙酮酸氧化;然而，乳酸氧化没有增加。胰岛素和DCA对丙酮酸和乳酸氧化的不同作用为心脏碳水化合物代谢的区室化提供了进一步的证据。这些结果可能对理解增加心脏碳水化合物代谢的有益作用的机制具有重要意义。
Despite the fact that lactate and pyruvate are potential substrates for energy production in vivo, our understanding of the control and regulation of carbohydrate metabolism is based principally on studies where glucose is the only available carbohydrate. Therefore, the purpose of this study was to determine the contributions of lactate, pyruvate, and glucose to energy production in the isolated, perfused rat heart over a range of insulin concentrations and after activation of pyruvate dehydrogenase with dichloroacetate (DCA). Hearts were perfused with physiological concentrations of [1-C-13] glucose, [U-C-13] lactate, [2-C-13]pyruvate, and unlabeled palmitate for 45 min. Hearts were freeze clamped, and C-13 NMR glutamate isotopomer analysis was performed on tissue extracts. Glucose, lactate, and pyruvate all contributed significantly to myocardial energy production; however, in the absence of insulin, glucose contributed only 25-30% of total pyruvate oxidation. Even under conditions where carbohydrates represented >95% of substrate entering the tricarboxylic acid (TCA) cycle, we found that glucose contributed at most 50-60% of total carbohydrate oxidation. Despite being present at only 0.1 mM, pyruvate contributed between similar to10% and 30% of total acetyl-CoA entry into the TCA cycle. We also found that insulin and DCA not only increased glucose oxidation but also exogenous pyruvate oxidation; however, lactate oxidation was not increased. The differential effects of insulin and DCA on pyruvate and lactate oxidation provide further evidence for compartmentation of cardiac carbohydrate metabolism. These results may have important implications for understanding the mechanisms underlying the beneficial effects of increasing cardiac carbohydrate metabolism.