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Cited by 378Metabolism, Diabetes, and CancerPI3K/AKT/mTOR signaling in cancerPancreatic function and diabetes

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

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Jiang, Zhen Y., Zhou, Qiong L., Coleman, Kerri A., Chouinard, My, Boese, Queta, Czech, Michael P.·2003·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1332633100PMC PMC164627
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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.

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Authors
Jiang, Z. Y., Zhou, Q. L., Coleman, K. A., Chouinard, M., Boese, Q., & Czech, M. P.
Affiliations
University of Massachusetts Chan Medical School (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2003-06-13
Volume
100
Issue
13
Pages
7569-7574
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1332633100
PMC
PMC164627
OpenAlex
W2013829707
Cited by
378
References
36
Citations by year
2026: 3 · 2025: 2 · 2024: 5 · 2023: 9 · 2022: 11 · 2021: 8 · 2020: 9 · 2019: 9 · 2018: 13 · 2017: 16 · 2016: 10 · 2015: 16 · 2014: 17 · 2013: 11 · 2012: 20
FWCI
12.90
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (DK 30648, DK-60837, R01DK060837, R01DK030648)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
insulin signaling, AKT1, AKT2, Akt, glucose transporter 4, GLUT4 translocation, hexose transport, phosphatidylinositol 3-kinase, adipocytes, 3T3-L1 cells, gene silencing, functional redundancy, glucose homeostasis
MeSH terms
Animals, Biological Transport, Cells, Cultured, Deoxyglucose, Fibroblasts, Glucose, Humans, Insulin, Microscopy, Fluorescence, Phosphorylation, Plasmids, Proto-Oncogene Proteins, Time Factors, Blotting, Western, Signal Transduction, 3T3 Cells, Protein Serine-Threonine Kinases, Adipocytes, Electroporation, Phosphatidylinositol 3-Kinases, Gene Silencing, RNA, Small Interfering, Proto-Oncogene Proteins c-akt, Mice

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