Smad5 regulates Akt2 expression and insulin-induced glucose uptake in L6 myotubes.

Abstract:

:Insulin-induced glucose uptake by skeletal muscle results from Akt2 activation and is severely impaired during insulin resistance. Recently, we and others have demonstrated that BMP9 improves glucose homeostasis in diabetic and non-diabetic rodents. However, the mechanism by which BMP9 modulates insulin action remains unknown. Here we demonstrate that Smad5, a transcription factor activated by BMP9, and Akt2, are upregulated in differentiated L6 myotubes. Smad5, rather than Smad1/8, is downregulated "in vivo" and "in vitro" by dexamethasone. Smad5 knockdown decreased Akt2 expression and serine phosphorylation and insulin-induced glucose uptake, and increased the expression of the lipid phosphatase Ship2. Additionally, binding of Smad5 to Akt2 gene is decreased in dexamethasone-treated rats and increased in L6 myotubes compared to myoblasts. The present study indicates that Smad5 regulates glucose uptake in skeletal muscle by controlling Akt2 expression and phosphorylation. These finding reveals Smad5 as a potential target for the therapeutic of type 2 diabetes.

journal_name

Mol Cell Endocrinol

authors

Anhê FF,Lellis-Santos C,Leite AR,Hirabara SM,Boschero AC,Curi R,Anhê GF,Bordin S

doi

10.1016/j.mce.2010.01.003

subject

Has Abstract

pub_date

2010-05-05 00:00:00

pages

30-8

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(10)00005-5

journal_volume

319

pub_type

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