title: Leucine facilitates the insulin-stimulated glucose uptake and insulin signaling in skeletal muscle cells: involving mTORC1 and mTORC2.
abstract: Leucine, a branched-chain amino acid, has been shown to promote glucose uptake and increase insulin sensitivity in skeletal muscle, but the exact mechanism remains unestablished. We addressed this issue in cultured skeletal muscle cells in this study. Our results showed that leucine alone did not have an effect on glucose uptake or phosphorylation of protein kinase B (AKT), but facilitated the insulin-induced glucose uptake and AKT phosphorylation. The insulin-stimulated glucose uptake and AKT phosphorylation were inhibited by the phosphatidylinositol 3-kinase inhibitor, wortmannin, but the inhibition was partially reversed by leucine. The inhibitor of mammalian target of rapamycin complex 1 (mTORC1), rapamycin, had no effect on the insulin-stimulated glucose uptake, but eliminated the facilitating effect of leucine in the insulin-stimulated glucose uptake and AKT phosphorylation. In addition, leucine facilitation of the insulin-induced AKT phosphorylation was neutralized by knocking down the core component of the mammalian target of rapamycin complex 2 (mTORC2) with specific siRNA. Together, these findings show that leucine can facilitate the insulin-induced insulin signaling and glucose uptake in skeletal muscle cells through both mTORC1 and mTORC2, implicating the potential importance of this amino acid in glucose homeostasis and providing new mechanistic insights.
authors.affiliation: Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, Hubei, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Yufang
authors.initials: Y
authors.lastname: Xiong
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Huailan
authors.initials: H
authors.lastname: Guo
authors.forename: Liping
authors.initials: L
authors.lastname: Hao
authors.forename: Ping
authors.initials: P
authors.lastname: Yao
authors.forename: Liegang
authors.initials: L
authors.lastname: Liu
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Yang
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007329:Insulin Antagonists / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D007930:Leucine / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D051381:Rats; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002352:Carrier Proteins; D007328:Insulin; D007329:Insulin Antagonists; D046912:Multiprotein Complexes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; C550254:rictor protein, rat; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D007930:Leucine; D005947:Glucose; D020123:Sirolimus; D000077191:Wortmannin