Přejít k obsahu
Merck
  • Alternative signaling pathways from IGF1 or insulin to AKT activation and FOXO1 nuclear efflux in adult skeletal muscle fibers.

Alternative signaling pathways from IGF1 or insulin to AKT activation and FOXO1 nuclear efflux in adult skeletal muscle fibers.

The Journal of biological chemistry (2020-09-02)
Sarah J Russell, Martin F Schneider
ANOTACE

Muscle atrophy is regulated by the balance between protein degradation and synthesis. FOXO1, a transcription factor, helps to determine this balance by activating pro-atrophic gene transcription when present in muscle fiber nuclei. Foxo1 nuclear efflux is promoted by AKT-mediated Foxo1 phosphorylation, eliminating FOXO1's atrophy-promoting effect. AKT activation can be promoted by insulin-like growth factor 1 (IGF1) or insulin via a pathway including IGF1 or insulin, phosphatidylinositol 3-kinase, and AKT. We used confocal fluorescence time-lapse imaging of FOXO1-GFP in adult isolated living muscle fibers maintained in culture to explore the effects of IGF1 and insulin on FOXO1-GFP nuclear efflux with and without pharmacological inhibitors. We observed that although AKT inhibitor blocks the IGF1- or insulin-induced effect on FOXO1 nuclear efflux, phosphatidylinositol 3-kinase inhibitors, which we show to be effective in these fibers, do not. We also found that inhibition of the protein kinase ACK1 or ATM contributes to the suppression of FOXO1 nuclear efflux after IGF1. These results indicate a novel pathway that has been unexplored in the IGF1- or insulin-induced regulation of FOXO1 and present information useful both for therapeutic interventions for muscle atrophy and for further investigative areas into insulin insensitivity and type 2 diabetes.

MATERIÁLY
Číslo produktu
Značka
Popis produktu

Sigma-Aldrich
Collagenase from Clostridium histolyticum, for general use, Type I, ≥125 CDU/mg solid
Sigma-Aldrich
Wortmannin, Ready Made Solution, from Penicillium funiculosum, ≥95% (HPLC)
Sigma-Aldrich
Akt Inhibitor VIII, Akti-1/2, InSolution, ≥95%, Isozyme-Selective
Sigma-Aldrich
KU-55933, ≥98% (HPLC)
Sigma-Aldrich
Insulin-like Growth Factor-I from mouse, IGF-I, recombinant, expressed in E. coli, lyophilized powder, suitable for cell culture