Acute inhibition of protein deacetylases does not impact skeletal muscle insulin action.
Acute inhibition of protein deacetylases does not impact skeletal muscle insulin action.
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蛋白质脱乙酰酶的急性抑制不会影响骨骼肌胰岛素的作用。
DOI：
10.1152/ajpcell.00159.2019
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Schenk,Simon
中科院分区：
文献类型：
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作者：
Martins,VitorF;Begur,Maedha;Lakkaraju,Shivani;Svensson,Kristoffer;Park,Ji;Hetrick,Byron;McCurdy,CarrieE;Schenk,Simon
是否组蛋白脱乙酰基酶（HDAC）和沉默调节蛋白家族的蛋白脱乙酰基酶调节胰岛素刺激的葡萄糖摄取，独立于他们的转录效应，还没有研究。我们的目的是确定HDACs和sirtuins在调节骨骼肌胰岛素作用中的非转录作用。在来自用HDAC（帕比司他汀A、帕比司他、TMP 195）和沉默调节蛋白抑制剂（烟酰胺）急性（1小时）处理的C57 BL/6 J小鼠的L 6肌管和骨骼肌中评估基础和胰岛素刺激的葡萄糖摄取和信号传导以及乙酰化。用HDAC抑制剂处理L 6肌管或用HDAC和沉默调节蛋白抑制剂的组合处理骨骼肌增加了微管蛋白和泛蛋白乙酰化，证明了HDAC和沉默调节蛋白脱乙酰酶活性的有效损害。尽管如此，基础或胰岛素刺激的葡萄糖摄取或胰岛素信号传导均未受到影响。HDAC和/或sirtuins的脱乙酰酶活性的急性降低不影响骨骼肌中的胰岛素作用。
Whether the histone deacetylase (HDAC) and sirtuin families of protein deacetylases regulate insulin-stimulated glucose uptake, independent of their transcriptional effects, has not been studied. Our objective was to determine the nontranscriptional role of HDACs and sirtuins in regulation of skeletal muscle insulin action. Basal and insulin-stimulated glucose uptake and signaling and acetylation were assessed in L6 myotubes and skeletal muscle from C57BL/6J mice that were treated acutely (1 h) with HDAC (trichostatin A, panobinostat, TMP195) and sirtuin inhibitors (nicotinamide). Treatment of L6 myotubes with HDAC inhibitors or skeletal muscle with a combination of HDAC and sirtuin inhibitors increased tubulin and pan-protein acetylation, demonstrating effective impairment of HDAC and sirtuin deacetylase activities. Despite this, neither basal nor insulin-stimulated glucose uptake or insulin signaling was impacted. Acute reduction of the deacetylase activity of HDACs and/or sirtuins does not impact insulin action in skeletal muscle.