Aberrant REDD1-mTORCL responses to insulin in skeletal muscle from type 2 diabetics

David L. Williamson, Cory M. Dungan, Abeer M. Mahmoud, Jacob T. Mey, Brian K. Blackburn, Jacob M. Haus

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33 Scopus citations


The objective of this study was to establish whether alterations in the REDD1-mTOR axis underlie skeletal muscle insensitivity to insulin in Type 2 diabetic (T2D), obese individuals. Vastus lateralis muscle biopsies were obtained from lean, control and obese, T2D subjects under basal and after a 2-h hyperinsulinemic (40 mU-m-2-min-1)-euglycemic (5 mM) clamp. Muscle lysates were examined for total REDD1, and phosphorylated Akt, S6 kinase 1 (S6K1), 4E-BP1, ERK1/2, and MEK1/2 via Western blot analysis. Under basal conditions [(-) insulin], T2D muscle exhibited higher S6K1 and ERK1/2 and lower 4E-BP1 phosphorylation (P < 0.05), as well as elevations in blood cortisol, glucose, insulin, glycosylated hemoglobin (P < 0.05) vs. lean controls. Following insulin infusion, whole body glucose disposal rates (GDR; mg/kg/ min) were lower (P < 0.05) in the T2D vs. the control group. The basal-to-insulin percent change in REDD1 expression was higher (P < 0.05) in muscle from the T2D vs. the control group. Whereas, the basal-to-insulin percent change in muscle Akt, S6K1, ERK1/2, and MEK1/2 phosphorylation was significantly lower (P < 0.05) in the T2D vs. the control group. Findings from this study propose a REDD1-regulated mechanism in T2D skeletal muscle that may contribute to whole body insulin resistance and may be a target to improve insulin action in insulin-resistant individuals.

Original languageEnglish
Pages (from-to)R855-R863
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number8
StatePublished - 2015

Bibliographical note

Publisher Copyright:
© 2015 the American Physiological Society.


  • Glucocorticoid
  • Insulin resistance
  • Signaling
  • mTOR

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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