Musclin inhibits insulin activation of Akt/protein kinase B in rat skeletal muscle.
Musclin is a muscle-derived secretory peptide that induces insulin resistance in vitro. We studied the effect of musclin (0.5 microg/ml) on insulin-stimulated glucose uptake in rat skeletal muscles and also the effect of rosiglitazone (0.4 microg/ml). Preincubation of muscles with musclin resulted in decreased insulin-stimulated glucose uptake. Musclin also reduced expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and liver X receptor alpha (LXRalpha) mRNAs, although expression of glucose transporter 4 mRNA was unaltered. Rosiglitazone attenuated the effects of musclin on glucose uptake and PPARgamma and LXRalpha mRNA expression. Western blotting demonstrated that activation of protein kinase B (Akt/PKB) in the insulin-signalling cascade was decreased by musclin but corrected by rosiglitazone. These findings suggest that musclin-induced impairment of insulin-stimulated glucose uptake in skeletal muscle is related to Akt/PKB inhibition and might be modulated by PPARgamma/LXRalpha.
Department of Endocrinology, The First Hospital, China Medical University, Shenyang, Liaoning, China.
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Liu
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Huo
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Pang
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Zong
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Meng
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Liu
D000818:Animals; D015153:Blotting, Western; D003720:Densitometry; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009124:Muscle Proteins / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D009124:Muscle Proteins; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose