Aberrant REDD1-mTORC1 responses to insulin in skeletal muscle from Type 2 diabetics.
Am J Physiol Regul Integr Comp Physiol
; 309(8): R855-63, 2015 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-26269521
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Músculo Esquelético
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Complexos Multiproteicos
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Diabetes Mellitus Tipo 2
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Serina-Treonina Quinases TOR
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Insulina
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Physiol Regul Integr Comp Physiol
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article