Mechanisms for the Sustained Effects of Prior Exercise on AS160 Phosphorylation and Insulin-Stimulated Glucose Transport in Rodent Skeletal Muscle.

Insulin Sensitivity;Bradykinin;Protein Phosphatase 1;Protein Phosphatase 2A;Protein Phosphatase 2B;Protein Phosphatase 2C;Physiology;Science;Kinesiology

Schweitzer, George GordonRui, Liangyou ;

University of Michigan

关键词: Insulin Sensitivity;    Bradykinin;    Protein Phosphatase 1;    Protein Phosphatase 2A;    Protein Phosphatase 2B;    Protein Phosphatase 2C;    Physiology;    Science;    Kinesiology;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/91584/ggschwei_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

One bout of exercise can lead to a long-lasting increase in insulin-stimulated glucose transport and a sustained increase in the phosphorylation of Akt Substrate of 160 kDa (AS160), a signaling protein proposed to be important for the post-exercise improvement in insulin sensitivity.The aims of the studies in this dissertation were to evaluate the roles of: 1) the Kallikrein-Kininogen System (KKS) in the increase in post-exercise insulin-stimulated glucose transport in rodent skeletal muscle; and 2) specific protein kinases and phosphatases for the sustained AS160 phosphorylation after acute exercise.KKS, previously proposed to be necessary for increased insulin-stimulated glucose transport after in vitro contractions, was studied with two genetic rodent models with deficits in KKS proteins: 1) mice null for the B2 receptor of bradykinin (B2R), and 2) rats deficient for plasma kininogen.The results indicated that neither the B2R in mice nor normal plasma kininogen levels in rats was essential for the post-exercise increase in insulin-stimulated glucose transport, suggesting that an intact KKS is not essential for enhanced muscle insulin sensitivity after exercise.The second part of the dissertation evaluated proteins regulating sustained AS160 phosphorylation after exercise.Results from these experiments demonstrated sustained phosphorylation of the Thr642 and Ser588 phospho-sites of AS160 in rat skeletal muscle 3-4 hours post-exercise.Each of the four known AS160 kinases (AMPK, Akt, RSK, and SGK) were studied, but only AMPK had greater phosphorylation immediately after exercise, and none had greater sustained phosphorylation in 3-4 hours post-exercise.Each of the four most abundant skeletal muscle serine/threonine phosphatases (PP1, PP2A, PP2B, and PP2C) was found to dephosphorylate AS160 in a cell-free assay, but only PP1 and PP2C were associated with AS160 based on co-immunoprecipitation analysis.PP1 and PP2C association with AS160 were unaltered post-exercise.The results suggest: 1) AMPK is likely to participate in the immediate post-exercise increase in AS160 phosphorylation; 2) sustained AS160^Thr642 and AS160^Ser588 phosphorylation 3-4 hours post-exercise is not attributable to greater phosphorylation of the known AS160 kinases; and 3) PP1 and PP2C may modulate AS160 phosphorylation in skeletal muscle because they are associated with AS160 and able to dephosphorylate AS160^Thr642 and AS160^Ser588.