PMID- 21527668 OWN - NLM STAT- MEDLINE DCOM- 20130708 LR - 20211203 IS - 1522-1601 (Electronic) IS - 0161-7567 (Linking) VI - 111 IP - 1 DP - 2011 Jul TI - An amino acid mixture enhances insulin-stimulated glucose uptake in isolated rat epitrochlearis muscle. PG - 163-9 LID - 10.1152/japplphysiol.01368.2010 [doi] AB - Protein and certain amino acids (AA) have been found to lower blood glucose. Although these glucose-lowering AA are important modulators of skeletal muscle metabolism, their impact on muscle glucose uptake remains unclear. We therefore examined how an AA mixture consisting of 2 mM isoleucine, 0.012 mM cysteine, 0.006 mM methionine, 0.0016 mM valine, and 0.014 mM leucine impacts skeletal muscle glucose uptake in the absence or presence of a submaximal (sINS) or maximal insulin (mINS) concentration. The AA mixture, sINS, and mINS significantly increased 2-[(3)H]deoxyglucose (2-DG) uptake by 63, 79, and 298% above basal, respectively. When the AA mixture was combined with sINS and mINS, 2-DG uptake was further increased significantly by 26% (P = 0.028) and 14% (P = 0.032), respectively. Western blotting analysis revealed that the AA mixture increased basal and sINS Akt substrate of 160 kDa (AS160) phosphorylation, while AA mixture did not change phosphorylation of Akt or mammalian target of rapamycin (mTOR) under these conditions. Interestingly, addition of the AA mixture to mINS increased phosphorylation of mTOR, Akt as well as AS160, compared with mINS alone. These data suggest that certain AA increase glucose uptake in the absence of insulin and augment insulin-stimulated glucose uptake in an additive manner. Furthermore, these effects appear to be mediated via a pathway that is independent from the canonical insulin cascade and therefore may prove effective as an alternative therapeutic treatment for insulin resistance. FAU - Kleinert, Maximilian AU - Kleinert M AD - Department of Kinesiology and Health Education, University of Texas at Austin, Austin, Texas 78712, USA. FAU - Liao, Yi-Hung AU - Liao YH FAU - Nelson, Jeffrey L AU - Nelson JL FAU - Bernard, Jeffrey R AU - Bernard JR FAU - Wang, Wanyi AU - Wang W FAU - Ivy, John L AU - Ivy JL LA - eng PT - Journal Article DEP - 20110428 PL - United States TA - J Appl Physiol (1985) JT - Journal of applied physiology (Bethesda, Md. : 1985) JID - 8502536 RN - 0 (Amino Acids) RN - 0 (GTPase-Activating Proteins) RN - 0 (Insulin) RN - 0 (TBC1D4 protein, rat) RN - 0 (Tubulin) RN - 020IUV4N33 (Phosphocreatine) RN - 04Y7590D77 (Isoleucine) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - 9G2MP84A8W (Deoxyglucose) RN - AE28F7PNPL (Methionine) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - GMW67QNF9C (Leucine) RN - HG18B9YRS7 (Valine) RN - K848JZ4886 (Cysteine) SB - IM MH - Adenosine Triphosphate/metabolism MH - Amino Acids/*metabolism MH - Animals MH - Biological Transport MH - Blotting, Western MH - Cysteine/metabolism MH - Deoxyglucose/*metabolism MH - *Energy Metabolism MH - GTPase-Activating Proteins/metabolism MH - In Vitro Techniques MH - Insulin/*metabolism MH - Isoleucine/metabolism MH - Kinetics MH - Leucine/metabolism MH - Male MH - Methionine/metabolism MH - Muscle, Skeletal/*metabolism MH - Phosphocreatine/metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - TOR Serine-Threonine Kinases/metabolism MH - Tubulin/metabolism MH - Valine/metabolism EDAT- 2011/04/30 06:00 MHDA- 2013/07/09 06:00 CRDT- 2011/04/30 06:00 PHST- 2011/04/30 06:00 [entrez] PHST- 2011/04/30 06:00 [pubmed] PHST- 2013/07/09 06:00 [medline] AID - japplphysiol.01368.2010 [pii] AID - 10.1152/japplphysiol.01368.2010 [doi] PST - ppublish SO - J Appl Physiol (1985). 2011 Jul;111(1):163-9. doi: 10.1152/japplphysiol.01368.2010. Epub 2011 Apr 28.