DOI: 10.1073/pnas.1332633100. Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing

Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing

10.1073/pnas.1332633100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Glucose homeostasis is controlled by insulin in part through the translocation of intracellular glucose transporter 4 to the plasma membrane in muscle and fat cells. Akt/protein kinase B downstream of phosphatidylinositol 3-kinase has been implicated in this insulin-signaling pathway, but results with a variety of reagents including Akt1 – / – and Akt2 – / – mice have been equivocal. Here we report the application of small interfering RNA-directed gene silencing to deplete both Akt1 and Akt2 in cultured 3T3-L1 adipocytes. Loss of Akt1 alone slightly impaired insulin-mediated hexose transport activity but had no detectable effect on glycogen synthase kinase (GSK)-3 phosphorylation. In contrast, depletion of Akt2 alone by 70% inhibited approximately half of the insulin responsiveness. Combined depletions of Akt1 plus Akt2 in these cells even more markedly attenuated insulin action on glucose transporter 4 movements, hexose transport activity, and GSK-3 phosphorylation. These data demonstrate a primary role of Akt2 in insulin signaling, significant functional redundancy of Akt1 and Akt2 isoforms in this pathway, and an absolute requirement of Akt protein kinases for regulation of glucose transport and GSK-3 in cultured adipocytes.

Bibliography

Jiang, Z. Y., Zhou, Q. L., Coleman, K. A., Chouinard, M., Boese, Q., & Czech, M. P. (2003). Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing. Proceedings of the National Academy of Sciences, 100(13), 7569â7574.

Authors 6

Zhen Y. Jiang (first)
Qiong L. Zhou (additional)
Kerri A. Coleman (additional)
My Chouinard (additional)
Queta Boese (additional)
Michael P. Czech (additional)

References 35 Referenced 303

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Dates

Type	When
Created	22 years, 2 months ago (June 24, 2003, 1:47 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 11:13 p.m.)
Indexed	1 month, 2 weeks ago (July 11, 2025, 6:45 a.m.)
Issued	22 years, 2 months ago (June 13, 2003)
Published	22 years, 2 months ago (June 13, 2003)
Published Online	22 years, 2 months ago (June 13, 2003)
Published Print	22 years, 2 months ago (June 24, 2003)

Funders 0

None

BibTeX

@article{Jiang_2003, title={Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1332633100}, DOI={10.1073/pnas.1332633100}, number={13}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Jiang, Zhen Y. and Zhou, Qiong L. and Coleman, Kerri A. and Chouinard, My and Boese, Queta and Czech, Michael P.}, year={2003}, month=jun, pages={7569–7574} }

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