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胰岛素对四氧嘧啶糖尿病大鼠心肌中丙酮酸脱氢酶相互转化的影响。

The effect of insulin on pyruvate dehydrogenase interconversion in heart muscle of alloxan-diabetic rats.

作者信息

Ohlen J, Siess E A, Löffler G, Wieland O H

出版信息

Diabetologia. 1978 Feb;14(2):135-9. doi: 10.1007/BF01263452.

DOI:10.1007/BF01263452
PMID:631458
Abstract

Evidence is presented for regulation by insulin of pyruvate dehydrogenase (pdh) interconversion in rat heart muscle in vivo and in vitro. In the alloxan diabetic rat the active (dephospho) enzyme amounted only to 12% of total PDH and was restored to 42% by insulin. Antilipolytic treatment of the dibetic animals was ineffective, indicating that the action of insulin was independent of a lowering of plasma non-esterified fatty acid concentration. On perfusion of isolated hearts from diabetic rats in the presence of glucose the proportion of pyruvate dehydrogenase in the active form remained low but was fully restored upon addition of insulin (2mU/ml) to the medium. No effect of insulin was obtained in the absence of glucose. The correlation between the rate of pyruvate decarboxylation in the perfused heart and of pyruvate dehydrogenase activity, in vitro, suggests that in the diabetic heart the entry of pyruvate into the citric acid cycle is largely controlled by covalent modification of the pyruvate dehydrogenase complex rather than by feedback inhibition. The possible role of insulin therein is discussed.

摘要

有证据表明,胰岛素在体内和体外均可调节大鼠心肌中丙酮酸脱氢酶(PDH)的相互转化。在四氧嘧啶糖尿病大鼠中,活性(去磷酸化)酶仅占总PDH的12%,而胰岛素可将其恢复至42%。对糖尿病动物进行抗脂解治疗无效,这表明胰岛素的作用与血浆非酯化脂肪酸浓度的降低无关。在葡萄糖存在的情况下,灌注糖尿病大鼠的离体心脏时,活性形式的丙酮酸脱氢酶比例仍然很低,但向培养基中添加胰岛素(2mU/ml)后可完全恢复。在没有葡萄糖的情况下,胰岛素没有作用。灌注心脏中丙酮酸脱羧速率与体外丙酮酸脱氢酶活性之间的相关性表明,在糖尿病心脏中,丙酮酸进入柠檬酸循环在很大程度上受丙酮酸脱氢酶复合物的共价修饰控制,而非反馈抑制。文中讨论了胰岛素在其中可能发挥作用。

相似文献

1
The effect of insulin on pyruvate dehydrogenase interconversion in heart muscle of alloxan-diabetic rats.胰岛素对四氧嘧啶糖尿病大鼠心肌中丙酮酸脱氢酶相互转化的影响。
Diabetologia. 1978 Feb;14(2):135-9. doi: 10.1007/BF01263452.
2
Regulation of pyruvate dehydrogenase in rat heart. Mechanism of regulation of proportions of dephosphorylated and phosphorylated enzyme by oxidation of fatty acids and ketone bodies and of effects of diabetes: role of coenzyme A, acetyl-coenzyme A and reduced and oxidized nicotinamide-adenine dinucleotide.大鼠心脏中丙酮酸脱氢酶的调节。脂肪酸和酮体氧化对去磷酸化和磷酸化酶比例的调节机制以及糖尿病的影响:辅酶A、乙酰辅酶A以及还原型和氧化型烟酰胺腺嘌呤二核苷酸的作用
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3
Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in starved and alloxan-diabetic rats.脂肪酸氧化抑制剂2-十四烷基缩水甘油酸对饥饿和四氧嘧啶糖尿病大鼠丙酮酸脱氢酶复合体活性的影响。
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5
Regulation of pyruvate dehydrogenase during infusion of fatty acids of varying chain lengths in the perfused rat heart.灌注大鼠心脏中不同链长脂肪酸输注期间丙酮酸脱氢酶的调节
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"In vitro" effects of insulin on the PDH complex of the isolated perfused heart of rats fed a sucrose-rich diet.胰岛素对喂食高蔗糖饮食大鼠离体灌注心脏的丙酮酸脱氢酶复合体的“体外”效应
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Effects of increased cardiac work on pyruvate dehydrogenase activity in hearts from diabetic animals.心脏工作负荷增加对糖尿病动物心脏丙酮酸脱氢酶活性的影响。
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The effect of ischaemia on the activity of pyruvate dehydrogenase complex in rat heart.缺血对大鼠心脏丙酮酸脱氢酶复合体活性的影响。
J Mol Cell Cardiol. 1984 Aug;16(8):723-33. doi: 10.1016/s0022-2828(84)80656-2.

引用本文的文献

1
Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid on pyruvate dehydrogenase complex activity in starved and alloxan-diabetic rats.脂肪酸氧化抑制剂2-十四烷基缩水甘油酸对饥饿和四氧嘧啶糖尿病大鼠丙酮酸脱氢酶复合体活性的影响。
Biochem J. 1982 Oct 15;208(1):53-60. doi: 10.1042/bj2080053.
2
Pyruvate dehydrogenase complex activity in normal and deficient fibroblasts.正常和成纤维细胞缺陷型中的丙酮酸脱氢酶复合物活性
J Clin Invest. 1981 May;67(5):1463-71. doi: 10.1172/jci110176.
3
Influence of insulin and glucose on pyruvate catabolism in perfused rat hindlimbs.

本文引用的文献

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The colorimetric micro-determination of long-chain fatty acids.长链脂肪酸的比色微量测定法。
Biochem J. 1963 Jul;88(1):7-10. doi: 10.1042/bj0880007.
2
Regulation of glucose uptake in muscle. I. The effects of insulin and anoxia on glucose transport and phosphorylation in the isolated, perfused heart of normal rats.肌肉中葡萄糖摄取的调节。I. 胰岛素和缺氧对正常大鼠离体灌流心脏中葡萄糖转运和磷酸化的影响。
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胰岛素和葡萄糖对灌注大鼠后肢丙酮酸分解代谢的影响。
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ATP-dependent inactivation of heart muscle pyruvate dehydrogenase and reactivation by Mg(++).心肌丙酮酸脱氢酶的ATP依赖性失活及Mg(++)介导的再激活
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Interconversion of pyruvate dehydrogenase in rat heart muscle upon perfusion with fatty acids or ketone bodies.大鼠心肌中丙酮酸脱氢酶在脂肪酸或酮体灌注时的相互转化。
FEBS Lett. 1971 Jul 1;15(4):295-298. doi: 10.1016/0014-5793(71)80641-5.
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Concentrations of glycerides and phospholipids in rat heart and gastrocnemius muscles. Effects of alloxan-diabetes and perfusion.大鼠心脏和腓肠肌中甘油酯和磷脂的浓度。四氧嘧啶糖尿病及灌注的影响。
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Insulin-like activity of dilute human serum assayed by an isolated adipose cell method.采用分离脂肪细胞法测定稀释人血清的胰岛素样活性。
Diabetes. 1965 Oct;14(10):643-9. doi: 10.2337/diab.14.10.643.
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Triglyceride breakdown in rat liver. The demonstration of three different lipases.大鼠肝脏中甘油三酯的分解。三种不同脂肪酶的证明。
Biochim Biophys Acta. 1969;187(2):173-85. doi: 10.1016/0005-2760(69)90025-3.
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Intracellular localization of pyruvate carboxylase and phosphoenolpyruvate carboxykinase in rat liver.大鼠肝脏中丙酮酸羧化酶和磷酸烯醇式丙酮酸羧激酶的细胞内定位
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Apparent reversal of insulin resistance in cardiac muscle in alloxan-diabetes by 2-bromostearate.2-溴硬脂酸盐可使四氧嘧啶糖尿病心肌中的胰岛素抵抗明显逆转。
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