Opitz D, Lenzen E, Schiffer T, Hermann R, Hellmich M, Bloch W, Brixius K, Brinkmann C
Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne, Cologne, Germany.
Outpatient Clinic for Sports Traumatology and Public Health Consultation, German Sport University Cologne, Cologne, Germany.
Int J Sports Med. 2014 Dec;35(13):1065-71. doi: 10.1055/s-0034-1371838. Epub 2014 Jul 10.
Patients suffering from type 2 diabetes mellitus (T2DM) often exhibit chronic elevated lactate levels which can promote peripheral insulin resistance by disturbing skeletal muscle insulin-signaling. Monocarboxylate transporter (MCT) proteins transfer lactate molecules through cellular membranes. MCT-1 and MCT-4 are the main protein isoforms expressed in human skeletal muscle, with MCT-1 showing a higher affinity (lower Km) for lactate than MCT-4. T2DM patients have reduced membranous MCT-1 proteins. Consequently, the lactate transport between muscle cells and the circulation as well as within an intracellular lactate shuttle, involving mitochondria (where lactate can be further metabolized), can be negatively affected. This study investigates whether moderate cycling endurance training (3 times per week for 3 months) can change skele-tal muscle MCT contents in T2DM men (n=8, years=56±9, body mass index (BMI)=32±4 kg/m(2)). Protein content analyses (immuno-histochemical stainings) were performed in bio-psies taken from the vastus lateralis muscle. Intracellular MCT-1 proteins were up-regulated (relative increase+89%), while intracellular MCT-4 contents were down-regulated (relative decrease - 41%) following endurance training. Sarcolemmal MCT-1 and MCT-4 did not change. The question of whether the training-induced up-regulation of intracellular MCT-1 leads to an improved lactate transport (and clearance) in T2DM patients requires further research.
2型糖尿病(T2DM)患者常表现出慢性乳酸水平升高,这会通过干扰骨骼肌胰岛素信号传导来促进外周胰岛素抵抗。单羧酸转运蛋白(MCT)可将乳酸分子转运穿过细胞膜。MCT-1和MCT-4是人类骨骼肌中表达的主要蛋白质异构体,MCT-1对乳酸的亲和力(较低的Km)高于MCT-4。T2DM患者的膜性MCT-1蛋白减少。因此,肌肉细胞与循环系统之间以及细胞内乳酸穿梭(涉及线粒体,乳酸可在其中进一步代谢)中的乳酸转运可能会受到负面影响。本研究调查了中度骑行耐力训练(每周3次,共3个月)是否能改变T2DM男性患者(n = 8,年龄= 56±9岁,体重指数(BMI)= 32±4 kg/m²)的骨骼肌MCT含量。对取自股外侧肌的活检组织进行蛋白质含量分析(免疫组织化学染色)。耐力训练后,细胞内MCT-1蛋白上调(相对增加89%),而细胞内MCT-4含量下调(相对减少41%)。肌膜上的MCT-1和MCT-4没有变化。训练诱导的细胞内MCT-1上调是否会改善T2DM患者的乳酸转运(和清除)这一问题仍需进一步研究。