Abstract
Insulin resistance is often accompanied by elevated circulating branched-chain amino acids (BCAA). We investigated the effects of insulin resistance on the mitochondrial BCAA transporter, SLC25A44, using a myotube model of insulin resistance. Insulin sensitivity and SLC25A44 expression were assessed via Western blot. Liquid chromatography-mass spectrometry was used to evaluate extracellular BCAA media content. Insulin resistance reduced pAkt activation following insulin stimulation but did not alter SLC25A44 expression. Under select conditions, insulin resistance led to the accumulation of extracellular BCAA.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
Abbreviations
- BCAA:
-
Branched-chain amino acids
- BCAT:
-
Branched-chain aminotransferase
- BCKDH:
-
Branched-chain alpha-keto acid dehydrogenase
- IRS-1:
-
Insulin receptor substrate 1
- LAT1:
-
L-type amino acid transporter 1
- PI3K:
-
Phosphoinositide 3 kinase
- SLC25A44:
-
Solute carrier family 25 member 44
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Funding
This work was supported by the Department of Health and Human Performance within the Congdon School of Health Sciences. Additional support was provided by the High Point University Undergraduate Research and Creative Works Small Project Support Grant (F-22-14). RMW was supported by the HPU Natural Science Fellows Program. Instrumentation support was provided by the Shimadzu Partnership for Academics, Research and Quality of Life (SPARQ) Program. We would also like to thank the Department of Physical Therapy (Congdon School of Health Sciences) for the use of shared lab space and equipment.
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CNR, RMW, and AJW conducted experiments and assisted with manuscript preparation. RAV conceived the study, conducted, and oversaw experiments, performed all statistical analyses, and oversaw manuscript preparation. All authors have read and approved the final manuscript.
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Rivera, C.N., Watne, R.M., Wommack, A.J. et al. The effect of insulin resistance on extracellular BCAA accumulation and SLC25A44 expression in a myotube model of skeletal muscle insulin resistance. Amino Acids 55, 1701–1705 (2023). https://doi.org/10.1007/s00726-023-03336-8
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DOI: https://doi.org/10.1007/s00726-023-03336-8