title: Effects of exercise on AMPK signaling and downstream components to PI3K in rat with type 2 diabetes.
abstract: Exercise can increase skeletal muscle sensitivity to insulin, improve insulin resistance and regulate glucose homeostasis in rat models of type 2 diabetes. However, the potential mechanism remains poorly understood. In this study, we established a male Sprague-Dawley rat model of type 2 diabetes, with insulin resistance and β cell dysfunction, which was induced by a high-fat diet and low-dose streptozotocin to replicate the pathogenesis and metabolic characteristics of type 2 diabetes in humans. We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and downstream components of phosphatidylinositol 3-kinase (PI3K) signaling pathways in the soleus. As a result, blood glucose, triglyceride, total cholesterol, and free fatty acid were significantly increased, whereas insulin level progressively declined in diabetic rats. Interestingly, chronic and acute exercise reduced blood glucose, increased phosphorylation and expression of AMPKα1/2 and the isoforms AMPKα1 and AMPKα2, and decreased phosphorylation and expression of AMPK substrate, acetyl CoA carboxylase (ACC). Chronic exercise upregulated phosphorylation and expression of AMPK upstream kinase, LKB1. But acute exercise only increased LKB1 expression. In particular, exercise reversed the changes in protein kinase C (PKC)ζ/λ phosphorylation, and PKCζ phosphorylation and expression. Additionally, exercise also increased protein kinase B (PKB)/Akt1, Akt2 and GLUT4 expression, but AS160 protein expression was unchanged. Chronic exercise elevated Akt (Thr(308)) and (Ser(473)) and AS160 phosphorylation. Finally, we found that exercise increased peroxisome proliferator-activated receptor-γ coactivator 1 (PGC1) mRNA expression in the soleus of diabetic rats. These results indicate that both chronic and acute exercise influence the phosphorylation and expression of components of the AMPK and downstream to PIK3 (aPKC, Akt), and improve GLUT4 trafficking in skeletal muscle. These data help explain the mechanism how exercise regulates glucose homeostasis in diabetic rats.
authors.affiliation: Department of Sport Medicine, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning Province, China. caoshicheng@tom.com
authors.forename: Shicheng
authors.initials: S
authors.lastname: Cao
authors.forename: Bowen
authors.initials: B
authors.lastname: Li
authors.forename: Xuejie
authors.initials: X
authors.lastname: Yi
authors.forename: Bo
authors.initials: B
authors.lastname: Chang
authors.forename: Beibei
authors.initials: B
authors.lastname: Zhu
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Lian
authors.forename: Zhaoran
authors.initials: Z
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.forename: Huili
authors.initials: H
authors.lastname: Liu
authors.forename: He
authors.initials: H
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D015444:Exercise; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008297:Male; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics
chemical_list: D007328:Insulin; D051266:Nuclear Respiratory Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D055372:AMP-Activated Protein Kinases