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Effect of valine on myotube insulin sensitivity and metabolism with and without insulin resistance.
Molecular and Cellular Biochemistry ( IF 4.3 ) Pub Date : 2020-03-28 , DOI: 10.1007/s11010-020-03720-y
Madison E Rivera 1 , Emily S Lyon 1 , Michele A Johnson 1 , Kyle L Sunderland 2 , Roger A Vaughan 1
Affiliation  

Population data have consistently demonstrated a correlation between circulating branched-chain amino acids (BCAA) and insulin resistance. Most recently valine catabolite, 3-hydroxyisobutyrate, has emerged as a potential cause of BCAA-mediated insulin resistance; however, it is unclear if valine independently promotes insulin resistance. It is also unclear if excess valine influences the ability of cells to degrade BCAA. Therefore, this study investigated the effect of valine on muscle insulin signaling and related metabolism in vitro. C2C12 myotubes were treated with varying concentrations (0.5 mM-2 mM) of valine for up to 48 h. qRT-PCR and western blot were used to measure metabolic gene and protein expression, respectively. Insulin sensitivity (indicated by pAkt:Akt), metabolic gene and protein expression, and cell metabolism were also measured following valine treatment both with and without varying levels of insulin resistance. Mitochondrial and glycolytic metabolism were measured via oxygen consumption and extracellular acidification rate, respectively. Valine did not alter regulators of mitochondrial biogenesis or glycolysis; however, valine reduced branched-chain alpha-keto acid dehydrogenase a (Bckdha) mRNA (but not protein) expression which was exacerbated by insulin resistance. Valine treatment had no effect on pAkt:Akt following either acute or 48-h treatment, regardless of insulin stimulation or varying levels of insulin resistance. In conclusion, despite consistent population data demonstrating a relationship between circulating BCAA (and related metabolites) and insulin resistance, valine does not appear to independently alter insulin sensitivity or worsen insulin resistance in the myotube model of skeletal muscle.

中文翻译:

缬氨酸对有无胰岛素抵抗的肌管胰岛素敏感性和代谢的影响。

人口数据一致地证明了循环支链氨基酸(BCAA)与胰岛素抵抗之间的相关性。最近,缬氨酸分解代谢产物3-羟基异丁酸酯已成为BCAA介导的胰岛素抵抗的潜在原因。然而,尚不清楚缬氨酸是否独立地促进胰岛素抵抗。还不清楚过量的缬氨酸是否会影响细胞降解BCAA的能力。因此,本研究调查了缬氨酸在体外对肌肉胰岛素信号传导和相关代谢的影响。用不同浓度(0.5 mM-2 mM)的缬氨酸处理C2C12肌管长达48小时。qRT-PCR和蛋白质印迹分别用于测量代谢基因和蛋白质表达。胰岛素敏感性(以pAkt:Akt表示),代谢基因和蛋白质表达,缬氨酸治疗后,无论是否存在不同水平的胰岛素抵抗,都应测量细胞的代谢和细胞代谢。线粒体和糖酵解代谢分别通过耗氧量和细胞外酸化率进行测量。缬氨酸没有改变线粒体生物发生或糖酵解的调节剂。然而,缬氨酸降低了支链α-酮酸脱氢酶a(Bckdha)mRNA(但不是蛋白质)的表达,这被胰岛素抵抗所加剧。缬氨酸治疗对急性或48小时治疗后的pAkt:Akt无影响,无论胰岛素刺激或胰岛素抵抗水平如何。总之,尽管一致的人群数据表明循环BCAA(和相关代谢产物)与胰岛素抵抗之间存在关联,
更新日期:2020-04-22
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