Fritz Tomas, Krämer David K, Karlsson Håkan K R, Galuska Dana, Engfeldt Peter, Zierath Juleen R, Krook Anna
Centre of Family Medicine, Karolinska University Hospital, Karolinska Institutet, 171 11 Stockholm, Sweden.
Diabetes Metab Res Rev. 2006 Nov-Dec;22(6):492-8. doi: 10.1002/dmrr.656.
Physical exercise provides health benefits for people with type 2 diabetes mellitus, partly by enhancing skeletal muscle insulin action. We tested the hypothesis that changes in expression of key genes in skeletal muscles relate to exercise-induced improvements in type 2 diabetic patients.
We determined mRNA expression of 20 selected genes following a self-supervised program of walking (> 150 min per week) over a 4-month period.
This level of physical activity improved clinical parameters in approximately half the participants, as determined by reduced hypertension and enhanced insulin sensitivity (defined by reduced plasma-insulin levels and improved homeostasis model assessment (HOMA)). Skeletal muscle mRNA expression of Cbl-associated protein (CAP), diacylglycerol kinase (DGK)delta, uncoupling protein (UCP) 3, nuclear respiratory factor (NRF)-1, and peroxisome proliferator-activated receptor (PPAR)delta tended to increase in type 2 diabetic patients with an improved clinical profile. Skeletal muscle protein expression of PPARdelta and UCP3 was increased significantly after physical exercise in patients with an improved clinical profile, but were unchanged in patients who did not show exercise-mediated improvements in clinical parameters.
This study provides clinical evidence that improvements in insulin sensitivity can be achieved in type 2 diabetic patients after individually executed low-intensity exercise training. Moreover, the positive clinical response to exercise is correlated with changes in skeletal muscle proteins involved in the regulation of mitochondrial biogenesis and metabolism. These changes in skeletal muscle gene expression offer a possible molecular explanation for the improvements in clinical outcomes.
体育锻炼对2型糖尿病患者有益健康,部分原因是增强了骨骼肌胰岛素作用。我们检验了以下假设:骨骼肌中关键基因的表达变化与2型糖尿病患者运动诱导的改善有关。
我们在4个月的时间里,根据一个自我监督的步行计划(每周>150分钟),测定了20个选定基因的mRNA表达。
通过降低高血压和提高胰岛素敏感性(由降低血浆胰岛素水平和改善稳态模型评估(HOMA)定义)来确定,这种运动量改善了大约一半参与者的临床参数。在临床状况改善的2型糖尿病患者中,与Cbl相关蛋白(CAP)、二酰甘油激酶(DGK)δ、解偶联蛋白(UCP)3、核呼吸因子(NRF)-1和过氧化物酶体增殖物激活受体(PPAR)δ的骨骼肌mRNA表达趋于增加。在临床状况改善的患者中,体育锻炼后PPARδ和UCP3的骨骼肌蛋白表达显著增加,但在临床参数未显示运动介导改善的患者中则无变化。
本研究提供了临床证据,表明2型糖尿病患者在进行个体化的低强度运动训练后,胰岛素敏感性可以得到改善。此外,运动的积极临床反应与参与线粒体生物发生和代谢调节的骨骼肌蛋白变化相关。骨骼肌基因表达的这些变化为临床结果的改善提供了一种可能的分子解释。