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急性糖尿病大鼠离体工作心脏中的三酰甘油周转率

Triacylglycerol turnover in isolated working hearts of acutely diabetic rats.

作者信息

Saddik M, Lopaschuk G D

机构信息

Department of Pediatrics and Department of Pharmacology, University of Alberta, Edmonton, Canada.

出版信息

Can J Physiol Pharmacol. 1994 Oct;72(10):1110-9. doi: 10.1139/y94-157.

Abstract

Although myocardial triacylglycerol may be a potentially important source of fatty acids for beta-oxidation in diabetes, few studies have measured triacylglycerol turnover directly in hearts from diabetic animals. In this study, myocardial triacylglycerol turnover was directly measured in isolated working hearts from streptozotocin-induced acutely diabetic rats. Hearts were initially perfused in the presence of 1.2 mM [14C]palmitate and 11 mM glucose for 1 h (pulse) to label the endogenous lipid pools, followed by a 10-min washout perfusion. Hearts were then perfused for another hour (chase) with buffer containing 11 mM glucose +/- 1.2 mM [3H]palmitate. During the chase, both 14CO2 and 3H2O production (measures of endogenous and exogenous fatty acid oxidation, respectively) were determined. A second series of hearts were perfused using the same protocol, except that unlabeled palmitate was used during the pulse and 11 mM [14C(U),5-3H]glucose +/- unlabeled palmitate was present during the chase. Both glycolysis (3H2O production) and glucose oxidation (14CO2 production) rates were measured in this series. Myocardial triacylglycerol levels were significantly higher in the diabetic rat hearts (77.5 +/- 4.6 vs. 33.7 +/- 4.1 mumol fatty acid/g dry mass in control hearts). In diabetic rat hearts chased with 1.2 mM palmitate, triacylglycerol lipolysis was increased, although endogenous [14C]palmitate oxidation rates were similar to control hearts and contributed 10.1% of overall ATP production. The majority of fatty acids derived from triacylglycerol lipolysis were released into the perfusate. In the absence of palmitate, both triacylglycerol lipolysis and endogenous [14C]palmitate oxidation rates were significantly increased in diabetic rat hearts, compared with control.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

尽管心肌三酰甘油可能是糖尿病中β氧化的脂肪酸潜在重要来源,但很少有研究直接测量糖尿病动物心脏中三酰甘油的周转率。在本研究中,直接测量了链脲佐菌素诱导的急性糖尿病大鼠离体工作心脏中的心肌三酰甘油周转率。心脏首先在含有1.2 mM [14C]棕榈酸酯和11 mM葡萄糖的条件下灌注1小时(脉冲)以标记内源性脂质池,随后进行10分钟的洗脱灌注。然后心脏再用含有11 mM葡萄糖±1.2 mM [3H]棕榈酸酯的缓冲液灌注1小时(追踪)。在追踪期间,分别测定了14CO2和3H2O的产生(分别为内源性和外源性脂肪酸氧化的指标)。第二组心脏采用相同方案进行灌注,不同之处在于脉冲期间使用未标记的棕榈酸酯,追踪期间存在11 mM [14C(U),5-3H]葡萄糖±未标记的棕榈酸酯。在这组实验中测量了糖酵解(3H2O产生)和葡萄糖氧化(14CO2产生)速率。糖尿病大鼠心脏中的心肌三酰甘油水平显著更高(糖尿病大鼠心脏为77.5±4.6 μmol脂肪酸/克干重,对照心脏为33.7±4.1 μmol脂肪酸/克干重)。在用1.2 mM棕榈酸酯追踪的糖尿病大鼠心脏中,三酰甘油脂解增加,尽管内源性[14C]棕榈酸酯氧化速率与对照心脏相似,且占总ATP产生的10.1%。源自三酰甘油脂解的大多数脂肪酸释放到灌注液中。在没有棕榈酸酯的情况下,与对照相比,糖尿病大鼠心脏中的三酰甘油脂解和内源性[14C]棕榈酸酯氧化速率均显著增加。(摘要截断于250字)

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