Costa-Júnior José M, Ferreira Sandra M, Protzek André O, Santos Gustavo J, Cappelli Ana P, Silveira Leonardo R, Zoppi Cláudio, de Oliveira Camila A M, Boschero Antonio C, Carneiro Everardo M, Rezende Luiz F
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, Campinas, SP, CEP 13083-865, Brazil.
Department of Biochemistry and Immunology, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo (USP), Ribeirão Preto, SP, Brazil.
PLoS One. 2015 Mar 30;10(3):e0118809. doi: 10.1371/journal.pone.0118809. eCollection 2015.
Endurance training improves peripheral insulin sensitivity in the liver and the skeletal muscle, but the mechanism for this effect is poorly understood. Recently, it was proposed that insulin clearance plays a major role in both glucose homeostasis and insulin sensitivity. Therefore, our goal was to determine the mechanism by which endurance training improves insulin sensitivity and how it regulates insulin clearance in mice.
Mice were treadmill-trained for 4 weeks at 70-80% of maximal oxygen consumption (VO2 max) for 60 min, 5 days a week. The glucose tolerance and the insulin resistance were determined using an IPGTT and an IPITT, respectively, and the insulin decay rate was calculated from the insulin clearance. Protein expression and phosphorylation in the liver and the skeletal muscle were ascertained by Western blot.
Trained mice exhibited an increased VO2 max, time to exhaustion, glucose tolerance and insulin sensitivity. They had smaller fat pads and lower plasma concentrations of insulin and glucose. Endurance training inhibited insulin clearance and reduced expression of IDE in the liver, while also inhibiting insulin secretion by pancreatic islets. There was increased phosphorylation of both the canonical (IR-AKT) and the non-canonical (CaMKII-AMPK-ACC) insulin pathways in the liver of trained mice, whereas only the CaMKII-AMPK pathway was increased in the skeletal muscle.
Endurance training improved glucose homeostasis not only by increasing peripheral insulin sensitivity but also by decreasing insulin clearance and reducing IDE expression in the liver.
耐力训练可改善肝脏和骨骼肌的外周胰岛素敏感性，但其作用机制尚不清楚。最近，有人提出胰岛素清除率在葡萄糖稳态和胰岛素敏感性中均起主要作用。因此，我们的目标是确定耐力训练改善胰岛素敏感性的机制以及它如何调节小鼠的胰岛素清除率。
小鼠在跑步机上以最大耗氧量（VO2 max）的70 - 80%进行训练，每周5天，每次60分钟，持续4周。分别使用腹腔注射葡萄糖耐量试验（IPGTT）和腹腔注射胰岛素耐量试验（IPITT）测定葡萄糖耐量和胰岛素抵抗，并根据胰岛素清除率计算胰岛素衰减率。通过蛋白质印迹法确定肝脏和骨骼肌中的蛋白质表达及磷酸化情况。
经过训练的小鼠表现出更高的VO2 max、耐力时间、葡萄糖耐量和胰岛素敏感性。它们的脂肪垫更小，血浆胰岛素和葡萄糖浓度更低。耐力训练抑制了胰岛素清除率，降低了肝脏中胰岛素降解酶（IDE）的表达，同时也抑制了胰岛的胰岛素分泌。训练小鼠肝脏中经典的（胰岛素受体 - 蛋白激酶B，IR - AKT）和非经典的（钙/钙调蛋白依赖蛋白激酶Ⅱ - 腺苷酸活化蛋白激酶 - 乙酰辅酶A羧化酶，CaMKII - AMPK - ACC）胰岛素信号通路的磷酸化均增加，而骨骼肌中仅CaMKII - AMPK信号通路增加。
耐力训练不仅通过增加外周胰岛素敏感性，还通过降低胰岛素清除率和减少肝脏中IDE的表达来改善葡萄糖稳态。
