Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery
Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery
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2 型糖尿病改变运动和恢复过程中葡萄糖和氨基酸代谢的代谢和转录特征
DOI：
10.1007/s00125-015-3584-x
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发表时间：
2015-08-01
期刊：
影响因子：
8.2
通讯作者：
Weigert, Cora
中科院分区：
文献类型：
--
作者：
Hansen, Jakob S.;Zhao, Xinjie;Weigert, Cora
目的/假设体育锻炼对预防和治疗2型糖尿病的疗效已被普遍接受。然而，该疾病对急性代谢反应的影响尚不清楚。为此，我们使用互补代谢组学/转录组学方法研究了2型糖尿病对运动诱导的血浆代谢物变化和肌肉转录反应的影响。方法对年龄、体脂百分比和最大耗氧量相匹配的2型糖尿病患者和健康对照者进行了60分钟自行车测力仪运动和180分钟恢复阶段，分析了9个时间点139种血浆代谢物和激素，以及3个时间点骨骼肌全基因组表达。结果运动后差异调节基因通路分析显示，与对照组相比，糖尿病参与者的GLUT4调节因子（SLC2A4RG、FLOT1、EXOC7、RAB13、rabgap1和cblb）、糖酵解（HK2、PFKFB1、PFKFB3、PFKM、fbp2和ldha）和胰岛素信号介质上调。值得注意的是，运动后，糖尿病参与者的乳酸和胰岛素水平以及葡萄糖的出现和消失都达到了正常水平。他们还发现了运动诱导的与氨基酸的生物合成和代谢有关的基因（PSPH，GATM， nos1和gldc）的代偿调节，这对氨基酸谱的差异（持续降低血浆中甘氨酸，半胱氨酸和精氨酸的水平）做出了反应。脂肪氧化（酰基肉碱）和脂肪分解（甘油）的标记并不表明糖尿病参与者在运动过程中代谢灵活性受损。结论/解释2型糖尿病个体表现出特定的运动调节基因表达。这些数据为改善与2型糖尿病相关的葡萄糖和氨基酸代谢紊乱的潜在机制提供了新的见解。
Aims/hypothesisThe therapeutic benefit of physical activity to prevent and treat type 2 diabetes is commonly accepted. However, the impact of the disease on the acute metabolic response is less clear. To this end, we investigated the effect of type 2 diabetes on exercise-induced plasma metabolite changes and the muscular transcriptional response using a complementary metabolomics/transcriptomics approach.MethodsWe analysed 139 plasma metabolites and hormones at nine time points, and whole genome expression in skeletal muscle at three time points, during a 60 min bicycle ergometer exercise and a 180 min recovery phase in type 2 diabetic patients and healthy controls matched for age, percentage body fat and maximal oxygen consumption ().ResultsPathway analysis of differentially regulated genes upon exercise revealed upregulation of regulators of GLUT4 (SLC2A4RG,FLOT1,EXOC7,RAB13,RABGAP1andCBLB), glycolysis (HK2,PFKFB1,PFKFB3,PFKM,FBP2andLDHA) and insulin signal mediators in diabetic participants compared with controls. Notably, diabetic participants had normalised rates of lactate and insulin levels, and of glucose appearance and disappearance, after exercise. They also showed an exercise-induced compensatory regulation of genes involved in biosynthesis and metabolism of amino acids (PSPH,GATM,NOS1andGLDC), which responded to differences in the amino acid profile (consistently lower plasma levels of glycine, cysteine and arginine). Markers of fat oxidation (acylcarnitines) and lipolysis (glycerol) did not indicate impaired metabolic flexibility during exercise in diabetic participants.Conclusions/interpretationType 2 diabetic individuals showed specific exercise-regulated gene expression. These data provide novel insight into potential mechanisms to ameliorate the disturbed glucose and amino acid metabolism associated with type 2 diabetes.