Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 2/20/2009
Publication Date: 4/2/2009
Publication URL: www.fasebj.org/cgi/content/meeting_abstract/23/1_MeetingAbstracts/228.3
Citation: Suryawan, A., Orellana, R., Nguyen, H., Davis, T. 2009. The abundance and activation of mTORC1 regulators in skeletal muscle of neonatal pigs are modulated by insulin, amino acids, and age [abstract]. Federation of American Societies for Experimental Biology Conference: Today's Research: Tomorrow's Health. Session: Nutrient-sensing mechanisms. April 18-22, 2009, New Orleans, Louisiana. Electronic Abstract: 23(1) Abstract No. 228.3. Interpretive Summary:
Technical Abstract: Previously we demonstrated that the insulin (INS) and amino acid (AA) -induced activation of the mammalian target of rapamycin complex 1 (mTORC1) is developmentally regulated in neonatal pigs. This study aimed to determine the effects of the post-prandial rise in INS and AA on the activation and abundance of mTORC1 regulators and how this is modified by development. Overnight-fasted 6- and 26-day-old pigs were infused for 2 h with saline (Control) or with INS or AA to achieve fed levels. Phosphorylation of Proline-rich Akt Substrate of 40 kDa (PRAS40) by protein kinase B alleviates the inhibitory effect of PRAS40 on mTORC1 activation. INS, but not AA, enhanced PRAS40 phosphorylation, and this effect was higher in younger pigs. AMP-activated protein kinase inactivates mTORC1 by phosphorylating raptor. Neither INS, AA, or age altered the phosphorylation of raptor. Rheb, vacuolar protein sorting mutant 34 (Vps34), and ras-related GTP-binding protein B (Rag B) are activators, while FK506-binding protein 38 (FKBP38) is an inhibitor of mTORC1. Neither INS, AA, or age altered the abundance of rheb, Vps34, or FKBP38. Although INS and AA had no effect, the abundance of Rag B was greater in young than in older pigs. Our results suggest that the higher mTORC1 activation in young than in older pigs is in part due to regulation by PRAS40 and the Rag GTPases.