Metformin counters the insulin-induced suppression of fatty acid oxidation and stimulation of triacylglycerol storage in rodent skeletal muscle
Metformin counters the insulin-induced suppression of fatty acid oxidation and stimulation of triacylglycerol storage in rodent skeletal muscle
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DOI：
10.1152/ajpendo.00272.2005
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发表时间：
2006-07-01
影响因子：
5.1
通讯作者：
Dyck, David J.
中科院分区：
文献类型：
--
作者：
Collier, Cheryl A.;Bruce, Clinton R.;Dyck, David J.
美托洛尔对抗胰岛素诱导的脂肪酸氧化抑制和啮齿动物骨骼肌中三酰甘油储存的刺激。Am J Physiol Endocrinol Metab 291：E182-E189，2006.首次出版于2006年2月14日; doi：10.1152/ajpendo. 00272.2005.-本研究考察了二甲双胍对啮齿动物氧化比目鱼肌（SOL）和糖酵解滑车上肌（EPT）中脂肪酸（FA）代谢的急性影响。SOL和EPT在不存在或存在2 mM二甲双胍以及存在或不存在胰岛素（10 mU/ml）的情况下孵育30或180 min。二甲双胍没有改变基础FA代谢，但抵消了胰岛素对FA氧化和掺入三酰甘油（TAG）的影响。具体而言，二甲双胍阻止了SOL中胰岛素诱导的FA氧化抑制，但未改变FA掺入脂质池。相比之下，在EPT中，二甲双胍减弱了胰岛素存在时FA与TAG的结合，但未改变FA氧化。在SOL中，二甲双胍导致AMP活化蛋白激酶α 2活性增加50%，并阻止胰岛素诱导的丙二酰辅酶A含量增加。在两种纤维类型中，二甲双胍均未显著改变基础和胰岛素刺激的葡萄糖氧化。所有的影响是相似的，无论他们是否在30或180分钟后测量。因为增加肌肉脂质储存和受损的FA氧化与胰岛素抵抗在这个组织中，二甲双胍逆转这些异常的能力，在肌肉FA代谢可能是二甲双胍改善葡萄糖清除和胰岛素敏感性的机制的一部分。目前的数据还表明，增加的葡萄糖清除率不是由于其增强的后续氧化。需要进行更多的研究以确定长期二甲双胍治疗是否对肌肉FA代谢具有类似的影响。
Metformin counters the insulin-induced suppression of fatty acid oxidation and stimulation of triacylglycerol storage in rodent skeletal muscle. Am J Physiol Endocrinol Metab 291: E182-E189, 2006. First published February 14, 2006; doi: 10.1152/ajpendo. 00272.2005.-The present study examined the acute effects of metformin on fatty acid (FA) metabolism in oxidative soleus (SOL) and glycolytic epitrochlearis (EPT) rodent muscle. SOL and EPT were incubated for either 30 or 180 min in the absence or presence of 2 mM metformin and with or without insulin (10 mU/ml). Metformin did not alter basal FA metabolism but countered the effects of insulin on FA oxidation and incorporation into triacylglyerol (TAG). Specifically, metformin prevented the insulin-induced suppression of FA oxidation in SOL but did not alter FA incorporation into lipid pools. In contrast, in EPT metformin blunted the incorporation of FA into TAG when insulin was present but did not alter FA oxidation. In SOL, metformin resulted in a 50% increase in AMP-activated protein kinase alpha 2 activity and prevented the insulin-induced increase in malonyl-CoA content. In both fiber types, basal and insulin-stimulated glucose oxidation were not significantly altered by metformin. All effects were similar regardless of whether they were measured after 30 or 180 min. Because increased muscle lipid storage and impaired FA oxidation have been associated with insulin resistance in this tissue, the ability of metformin to reverse these abnormalities in muscle FA metabolism may be a part of the mechanism by which metformin improves glucose clearance and insulin sensitivity. The present data also suggest that increased glucose clearance is not due to its enhanced subsequent oxidation. Additional studies are warranted to determine whether chronic metformin treatment has similar effects on muscle FA metabolism.