Differential Contribution of Insulin and Amino Acids to the mTORC1-Autophagy Pathway in the Liver and Muscle |
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Authors: | Takako Naito Akiko Kuma Noboru Mizushima |
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Affiliation: | From the ‡Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.;the §Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan, and ;the ¶Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Tokyo 102-0076, Japan |
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Abstract: | Autophagy is a highly inducible intracellular degradation process. It is generally induced by nutrient starvation and suppressed by food intake. Mammalian (or mechanistic) target of rapamycin complex 1 (mTORC1) is considered to be the major regulator of autophagy, but the precise mechanism of in vivo regulation remains to be fully characterized. Here, we examined the autophagy-suppressive effect of glucose, insulin, and amino acids in the liver and muscle in mice starved for 1 day. Refeeding after starvation with a standard mouse chow rapidly suppressed autophagy in both tissues, and this suppression was inhibited by rapamycin administration almost completely in the liver and partially in muscle, confirming that mTORC1 is indeed a crucial regulator in vivo. As glucose administration showed no major suppressive effect on autophagy, we examined the role of insulin and amino acids using hyperinsulinemic-euglycemic clamp and intravenous amino acid infusion techniques. Insulin administration showed a clear effect on the mTORC1-autophagy pathway in muscle, but had only a very weak effect in the liver. By contrast, amino acids were able to regulate the mTORC1-autophagy pathway in the liver, but less effectively in muscle. These results suggest that autophagy is differentially regulated by insulin and amino acids in a tissue-dependent manner. |
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Keywords: | Amino Acid Autophagy Insulin mTOR Complex (mTORC) Protein Degradation |
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