Fasting serum amino acids concentration is associated with insulin resistance and pro-inflammatory cytokines
Fasting serum amino acids concentration is associated with insulin resistance and pro-inflammatory cytokines
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DOI：
10.1016/j.diabres.2018.03.028
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发表时间：
2018-06-01
影响因子：
5.1
通讯作者：
Kim, Jeong-Ho
中科院分区：
文献类型：
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作者：
Lee, Sang-Guk;Yim, Ye Seal;Kim, Jeong-Ho
目的：探讨2型糖尿病(T2 DM)和空腹血糖受损(IFG)患者血清氨基酸(AAs)水平的变化，并探讨其发生机制。方法：对56例T2 DM患者、69例IFG患者和73例健康对照的空腹血清AAs、TNF-α和IL-6进行检测。结果：除支链氨基酸外，T2 DM患者血清中谷氨酸、赖氨酸、苯丙氨酸、精氨酸、丙氨酸、酪氨酸、天冬氨酸等空腹血清氨基酸水平高于正常血糖对照组。这些血清AA浓度与空腹血糖、胰岛素抵抗的稳态模型评估(HOMA-IR)和促炎细胞因子呈正相关。此外，HOMA-IR和促炎细胞因子是血清AA水平的两个重要独立预测因子。体外实验表明，棕榈酸酯处理C2C12肌管可诱导胰岛素抵抗，增加促炎细胞因子基因表达，增加MAFbx基因和蛋白表达。结论：空腹血清AAs升高可作为胰岛素抵抗的早期表现。胰岛素抵抗和炎性细胞因子诱导的肌肉蛋白分解增加可能是血清AA水平升高的机制之一。(C)2018爱思唯尔B.V.保留所有权利。
Aims: We evaluated specific alterations in amino acids (AAs) profile in patients with type 2 diabetes mellitus (T2DM) and impaired fasting glucose (IFG) compared with healthy controls In addition, we tried to find the mechanisms behind these AA alterations.Methods: Twenty AAs, TNF-alpha, and IL-6 were analyzed in fasting serum samples from a total of 198 individuals (56 drug-naive patients with T2DM, 69 patients IFG, and 73 healthy controls). The C2C12 mouse myoblast cell lines were used to examine the changes of MAFbx and MuRF1 expressions, which are muscle specific E3 ligases acting as major mediators of skeletal muscle proteolysis, after development of insulin resistance induced by palmitate treatment.Results: In addition to branched chain amino acids BCAAs, fasting serum AAs such as glutamic acid, lysine, phenylalanine, arginine, alanine, tyrosine, aspartic acid, were higher in patients with T2DM and intermediately elevated in patients with IFG compared with normoglycemic controls. These serum AA concentrations positively correlated with fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR), and pro-inflammatory cytokines. In addition, HOMA-IR and pro-inflammatory cytokines were two important independent predictors of serum AA levels. In vitro experiments showed that palmitate treatment in C2C12 myotubes induced insulin resistance, increased pro-inflammatory cytokine gene expression, and increased MAFbx gene and protein expression.Conclusions: The increase in fasting serum AAs can be an early manifestation of insulin resistance. Increased muscle proteolysis induced by insulin resistance and inflammatory cytokines can be a possible mechanism for the rise in serum AA levels. (C) 2018 Elsevier B.V. All rights reserved.