Exercise (E) in ZDF Rats Delays T2DM, Protects Muscle Protein Synthetic Pathways, and Alleviates Amino Acid (AA) Restraint of Glucose Uptake
Canadian Journal of Diabetes(2008)
摘要
Muscle protein metabolism is abnormal in T2DM, but improved by therapeutic interventions. T2DM is delayed dramatically in ZDF rats by E preventing insulin hypersecretion decline, and less by restraint stress (S), via reduced basal neuroendocrine activity and hyperinsulinemia to between E and untreated controls (OC). Elevated AA attenuate insulin-mediated glucose uptake. We hypothesized that E and S decrease T2DM effects on skeletal muscle synthetic and proteolytic pathways. Groups of ≥ 7 ♂ ZDF that underwent 1 h/d, 5d/wk E or S from ages 6 – 19 wk were compared OC and lean (LC) controls. Chow intake and growth were the same in E and OC, slightly less in S, and all were greater than LC. Together, all obese rats had greater (P < 0.05 vs LC) gastronemius muscle phosphorylation (ph) of Akt (82%) and mTOR (58%) (activation) and of translation inhibitor 4E-BP1 (11%) (less inhibition), consistent with increased protein synthesis. Serum total branched- chain AA (BCAA) in OC and S were 50% > LC (P < 0.05). In contrast, E attenuated phAkt and phmTOR to those of LC, but ph4EBP1 remained greater (P < 0.05). Notably, BCAA in E were = LC. Surprisingly, mRNA expression of indices of ubiquitin-dependent proteolysis were unaffected, suggesting no increase in this pathway. Across 4 groups, correlations existed between many essential AA and phAkt and phS6K1 and between phAkt and glucose, fed (P = 0.005), and AUC (P = 0.003). Thus: metabolic dysregulation in S and OC (VS. LC) was associated with higher AA, increased translation initiation signaling, yet marked insulin resistance and T2DM. In contrast, E maintained signaling and AA closer to LC, so delayed T2DM could result from sustained hyperinsulinemia plus lesser AA attenuation of insulin-mediated glucose uptake.
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关键词
zdf rats delays t2dm,glucose uptake,exercise
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