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Fructose-induced AGEs-RAGE signaling in skeletal muscle contributes to impairment of glucose homeostasis

机译:骨肉肌肉中的果糖诱导的年龄 - 愤怒信号传导有助于葡萄糖稳定性的损伤

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摘要

Increased fructose intake has been linked to the development of dyslipidemia, obesity and impaired glucose tolerance. Due to its specific metabolic fate, fructose impairs normal lipid and carbohydrate metabolism and facilitates the non-enzymatic glycation reaction leading to enhanced accumulation of advanced glycation end products (AGEs). However, the formation of fructose-AGEs under in vivo setup and its tissue specific accumulation is less explored. Here, we investigated the impact of high fructose on AGEs accumulation in skeletal muscle and its causal role in impaired glucose homeostasis. In L6 rat skeletal muscle cells, chronic exposure to fructose induced AGEs accumulation and the cellular level of the receptor for AGEs (RAGE) and the effect was prevented by pharmacological inhibition of glycation. Under in vivo settings, Sprague Dawley rats exposed to 20% fructose in drinking water for 16 weeks, displayed increased fasting glycemia, impaired glucose tolerance, decreased skeletal muscle Akt (Ser-473) phosphorylation, and enhanced triglyceride levels in serum, liver and gastrocnemius muscle. We also observed a high level of AGEs in serum and gastrocnemius muscle of fructose-supplemented animals, associated with methylglyoxal accumulation and up regulated expression of RAGE in gastrocnemius muscle. Treatment with aminoguanidine inhibited fructose-induced AGEs accumulation and normalized the expression of RAGE and Dolichyl-Diphosphooligosaccharide-Protein Glycosyltransferase (DDOST) in gastrocnemius muscle. Inhibition of AGEs-RAGE axis counteracted fructose-mediated glucose intolerance without affecting energy metabolism. These data reveal diet-derived AGEs accumulation in skeletal muscle and the implication of tissue specific AGEs in metabolic derangement, that may open new perspectives in pathogenic mechanisms and management of metabolic diseases. (C) 2019 Elsevier Inc. All rights reserved.
机译:增加的果糖摄入量与血脂血症,肥胖和葡萄糖耐量受损的发展有关。由于其特定的代谢命运,果糖损害了正常的脂质和碳水化合物代谢,并促进了非酶促糖化反应,导致提高了先进的糖化末端产物(年龄)的积累。然而,探索了体内设置下的果糖 - 年龄及其组织特异性积累。在这里,我们调查了高果糖对骨骼肌中患者积累的影响及其在葡萄糖稳态受损的因果作用。在L6大鼠骨骼肌细胞中,慢性暴露于果糖诱导的年龄积累和受体的细胞水平(愤怒),通过药理抑制糖化的药物抑制来预防效果。在体内设置下,Sprague Dawley大鼠暴露于20%的饮用水果糖16周,呈现出速度血糖,葡萄糖耐量有损,骨骼肌损伤(Ser-473)磷酸化,血清,肝脏和胃肠中的增强甘油三酯水平增加肌肉。我们还观察到血清和腓肠肌肌肉的高级别,果糖补充动物的肌肉,与甲基乙二醛积累和胃肠肌肉中的愤怒表达相关。用氨基胍治疗抑制果糖诱导的年龄积累,并标准化了胃肠杆菌肌肉中愤怒和越氯基二磷寡糖 - 蛋白糖基转移酶(DDOST)的表达。抑制年龄愤怒轴的抑制抵消了果糖介导的葡萄糖不耐受,而不会影响能量代谢。这些数据揭示了骨骼肌中的饮食衍生的年龄积累以及组织特异性年龄在代谢紊乱中的含义,这可能在致病机制和代谢疾病的管理中开辟新的视角。 (c)2019 Elsevier Inc.保留所有权利。

著录项

  • 来源
    《The Journal of Nutritional Biochemistry》 |2019年第2019期|共10页
  • 作者单位

    Cent Drug Res Inst CSIR Biochem Div Sec 10 Jankipuram Extens Sitapur Rd Lucknow 226031 Uttar Pradesh India;

    Cent Drug Res Inst CSIR Biochem Div Sec 10 Jankipuram Extens Sitapur Rd Lucknow 226031 Uttar Pradesh India;

    Cent Drug Res Inst CSIR Biochem Div Sec 10 Jankipuram Extens Sitapur Rd Lucknow 226031 Uttar Pradesh India;

    Cent Drug Res Inst CSIR Biochem Div Sec 10 Jankipuram Extens Sitapur Rd Lucknow 226031 Uttar Pradesh India;

    Cent Drug Res Inst CSIR Biochem Div Sec 10 Jankipuram Extens Sitapur Rd Lucknow 226031 Uttar Pradesh India;

    Cent Drug Res Inst CSIR Biochem Div Sec 10 Jankipuram Extens Sitapur Rd Lucknow 226031 Uttar Pradesh India;

    Cent Drug Res Inst CSIR Pharmacokinet &

    Metab Div Lucknow 226031 Uttar Pradesh India;

    Cent Drug Res Inst CSIR Pharmacokinet &

    Metab Div Lucknow 226031 Uttar Pradesh India;

    Cent Drug Res Inst CSIR Biochem Div Sec 10 Jankipuram Extens Sitapur Rd Lucknow 226031 Uttar Pradesh India;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

    Fructose; AGEs; Glycation; Skeletal muscle; Glucose homeostasis;

    机译:果糖;年龄;糖化;骨骼肌;葡萄糖稳态;

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