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

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

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 (US)
Pages (from-to)R855-R863
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume309
Issue number8
DOIs
StatePublished - Jan 1 2015

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Skeletal Muscle
Insulin
Ribosomal Protein S6 Kinases
Muscles
Control Groups
Phosphorylation
Quadriceps Muscle
Glycosylated Hemoglobin A
Insulin Resistance
Hydrocortisone
Blood Glucose
Western Blotting
Biopsy
Glucose

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Williamson, IV, David L. ; Dungan, Cory M. ; Mahmoud, Abeer M. ; Mey, Jacob T. ; Blackburn, Brian K. ; Haus, Jacob M. / Aberrant REDD1-mTORCL responses to insulin in skeletal muscle from type 2 diabetics. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2015 ; Vol. 309, No. 8. pp. R855-R863.
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Aberrant REDD1-mTORCL responses to insulin in skeletal muscle from type 2 diabetics. / Williamson, IV, David L.; Dungan, Cory M.; Mahmoud, Abeer M.; Mey, Jacob T.; Blackburn, Brian K.; Haus, Jacob M.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 309, No. 8, 01.01.2015, p. R855-R863.

Research output: Contribution to journalArticle

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T1 - Aberrant REDD1-mTORCL responses to insulin in skeletal muscle from type 2 diabetics

AU - Williamson, IV, David L.

AU - Dungan, Cory M.

AU - Mahmoud, Abeer M.

AU - Mey, Jacob T.

AU - Blackburn, Brian K.

AU - Haus, Jacob M.

PY - 2015/1/1

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N2 - 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.

AB - 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.

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