Adiponectin Sensitizes Insulin Signaling by Reducing p70 S6 Kinase-mediated Serine Phosphorylation of IRS-1
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Adiponectin functions as an insulin sensitizer, and yet the underlying molecular mechanism(s) remains largely unknown. We found that treating C2C12 myotubes with adiponectin or rapamycin enhanced the ability of insulin to stimulate IRS-1 tyrosine phosphorylation and Akt phosphorylation, concurrently with reduced p70 S6 kinase phosphorylation at Thr389 as well as IRS-1 phosphorylation at Ser302 and Ser636/639. Overexpression of dominant-negative AMP kinase (AMPK), but not dominant-negative p38 MAPK, reduced the insulin-sensitizing effect of adiponectin. Rapamycin, but not adiponectin, enhanced insulin-stimulated Akt phosphorylation in HeLa cells, which lack LKB1, and exogenous expression of LKB1 in HeLa cells rescued the insulin-sensitizing effect of adiponectin. Finally, overexpression of wild-type Rheb (Ras homology-enriched in brain) or the TSC2 mutant lacking the AMPK phosphorylation site (TSC2S1345A) inhibited the insulin-sensitizing effect of adiponectin in C2C12 cells. These results indicate that activation of the LKB1/AMPK/TSC1/2 pathway alleviates the p70 S6 kinase-mediated negative regulation of insulin signaling, providing a mechanism by which adiponectin increases insulin sensitivity in cells.
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Activation of AMPK by adiponectin enhances the ability of insulin to stimulate IRS1 and Akt phosphorylation concurrently, with reduced S6K1 phosphorylation at T389 as well as IRS1 phosphorylation at S302 and S636/639.
“Recent studies have shown that the activation of AMPK by adiponectin enhances the ability of insulin to stimulate IRS1 and Akt phosphorylation concurrently, with reduced S6K1 phosphorylation at T389 as well as IRS1 phosphorylation at S302 and S636/639 [160].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [160]
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- Authors
- Wang, C., Mao, X., Wang, L., Liu, M., Wetzel, M. D., Guan, K.-L., Dong, L. Q., & Liu, F.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- University of Michigan (US)
- Corresponding author
- Liu, Feng
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 282
- Issue
- 11
- Pages
- 7991-7996
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2164663878
- Cited by
- 210
- References
- 37
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 11 · 2022: 5 · 2021: 15 · 2020: 12 · 2019: 10 · 2018: 10 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 11 · 2013: 18 · 2012: 16
- FWCI
- 12.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK069930)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- adiponectin, insulin sensitivity, insulin signaling, IRS-1 serine phosphorylation, p70 S6 kinase, Akt phosphorylation, LKB1, AMPK, TSC2, Rheb, TSC1, rapamycin, myotubes
- MeSH terms
- Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Animals, Insulin, Models, Biological, Phosphoproteins, Phosphorylation, Serine, Transfection, Signal Transduction, Protein Serine-Threonine Kinases, Tumor Suppressor Proteins, Ribosomal Protein S6 Kinases, 70-kDa, p38 Mitogen-Activated Protein Kinases, Mice, Adiponectin, AMP-Activated Protein Kinases, Insulin Receptor Substrate Proteins
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