Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 559, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2022.111800
Keywords
Leucine; Isoleucine; Valine; pAkt; Akt; Insulin resistance; Diabetes
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Insulin resistance, but not BCAA treatment, promotes extracellular BCAA accumulation independent of changes in LAT1 content, suggesting insulin resistance as a causal agent of extracellular BCAA accumulation.
Purpose: Type 2 diabetes is characterized by reduced insulin sensitivity which correlates with increased circu-lating BCAA. These experiments investigated the effects of insulin resistance with and without excess BCAA on myotube insulin sensitivity and L-type amino acid transporter-1 (LAT1).Methods: C2C12 myotubes were treated with or without excess BCAA for 1 or 6 days, both with and without insulin resistance. Western blot was used to assess insulin sensitivity and LAT1 content. Liquid chromatography -mass spectrometry was used to evaluate BCAA media content.Results: Insulin resistance was associated with significantly increased extracellular BCAA accumulation inde-pendent of LAT1 content. Conversely, prior BCAA treatment was not associated with extracellular BCAA accu-mulation regardless of level of insulin sensitivity.Conclusion: These data suggest insulin resistance, but not BCAA treatment, promotes extracellular BCAA accu-mulation independent of changes in LAT1 content, implicating insulin resistance as a causal agent of extracel-lular BCAA accumulation.
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