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Glucose Metabolism Activation by SHIP2 Inhibitors via Up-Regulation of GLUT1 Gene in L6 Myotubes

Glucose Metabolism Activation by SHIP2 Inhibitors via Up-Regulation of GLUT1 Gene in L6 Myotubes

Akira Suwa, Takeshi Kurama, Tadashi Yamamoto, Akihiko Sawada, Teruhiko Shimokawa, Ichiro Aramori

Eur J Pharmacol. 2010 Sep 10;642(1-3):177-82.

PMID: 20558154

Abstract:

Lipid phosphatase SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2) plays an important role in the regulation of insulin signaling. In this report, we identified AS1938909, a novel small-molecule SHIP2 inhibitor. AS1938909 showed potent inhibition of SHIP2 (Ki=0.44 microuM) and significant selectivity over other related phosphatases. Further, AS1938909 increased Akt phosphorylation, glucose consumption, and glucose uptake in L6 myotubes. Treatment of L6 myotubes with SHIP2 inhibitors for 48 h significantly induced expression of GLUT1 mRNA, but not that of GLUT4. These results suggest that pharmacological inhibition of SHIP2 activates glucose metabolism due, at least in part, to up-regulation of GLUT1 gene expression.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42416418	SHIP2 Inhibitor, AS1938909			Price

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