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.
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Abbreviations
- BCAA:
-
Branched-chain amino acids
- 2-DG:
-
2-Deoxy-d-glucose
- 2DG6P:
-
2-Deoxyglucose-6-phosphate
- 4EBP1:
-
eIF4E-binding proteins
- G6PDH:
-
Glucose-6-phosphate dehydrogenase
- IRS-1:
-
Insulin receptor substrate-1
- mTOR:
-
Mammalian target of rapamycin
- mTORC1:
-
Mammalian target of rapamycin complex 1
- mTORC2:
-
Mammalian target of rapamycin complex 2
- PI3-K:
-
Phosphatidylinositol 3-kinase
- PKB/AKT:
-
Protein kinase B
- Rictor:
-
Rapamycin-insensitive companion of mTOR
- S6K:
-
Ribosomal protein S6 kinase
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Acknowledgments
This work was supported by The National Natural Science Foundation of China (NSFC) (Grant No. 30800907 and No. 81373006) (to X.Y.), the Fundamental Research Funds for the Central Universities (HUST:2013TS006) (to X.Y.).
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The authors declare that they have no competing financial interests.
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Liu, H., Liu, R., Xiong, Y. et al. Leucine facilitates the insulin-stimulated glucose uptake and insulin signaling in skeletal muscle cells: involving mTORC1 and mTORC2. Amino Acids 46, 1971–1979 (2014). https://doi.org/10.1007/s00726-014-1752-9
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DOI: https://doi.org/10.1007/s00726-014-1752-9