The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
5′-AMP-activated Protein Kinase Phosphorylates IRS-1 on Ser-789 in Mouse C2C12 Myotubes in Response to 5-Aminoimidazole-4-carboxamide Riboside
Open accessAbstract
Exercise is known to increase insulin sensitivity and is an effective form of treatment for the hyperglycemia observed in type 2 diabetes. Activation of 5'-AMP-activated protein kinase (AMPK) by 5-aminoimidazole-4-carboxamide riboside (AICAR), exercise, or electrically stimulated contraction leads to increased glucose transport in skeletal muscle. Here we report the first evidence of a direct interaction between AMPK and the most upstream component of the insulin-signaling cascade, insulin receptor substrate-1 (IRS-1). We find that AMPK rapidly phosphorylates IRS-1 on Ser-789 in cell-free assays as well as in mouse C2C12 myotubes incubated with AICAR. In the C2C12 myotubes activation of AMPK by AICAR matched the phosphorylation of IRS-1 on Ser-789. This phosphorylation correlates with a 65% increase in insulin-stimulated IRS-1-associated phosphatidylinositol 3-kinase activity in C2C12 myotubes preincubated with AICAR. The binding of phosphatidylinositol 3-kinase to IRS-1 was not affected by AICAR. These results demonstrate the existence of an interaction between AMPK and early insulin signaling that could be of importance to our understanding of the potentiating effects of exercise on insulin signaling.
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“It has been reported that AMPK rapidly phosphorylates IRS1 on S789 in vitro and treatment with AICAR increases IRS1 S789 phosphorylation in mouse C2C12 myotubes, suggesting a possible link between the potentiating effects of exercise on insulin signaling [145].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [145]
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Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6
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“One possible explanation for the enhanced insulin sensitivity postexercise relates to the finding that AMPK phosphorylates insulin receptor substrate 1 (IRS-1) at Ser789 in vitro and that AICAR treatment in C2C12 muscle cells increases IRS-1 Ser-789 phosphorylation and insulin-stimulated IRS-1 associated PI3K activity…”
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“equivalent to Ser789 in rat IRS1, shown to be phosphorylated by AMPK ( Jakobsen et al, 2001 ).”
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“Interestingly, treatment of C2C12 muscle cells with the AMPK agonist 5-aminoimidazole-4carboxamide-1-β-D-ribofuranoside (AICAR) has an additive effect, with insulin, to promote IRS1-associated PI3K activity [145].”
Background
Metadata
- Authors
- Jakobsen, S. N., Hardie, D. G., Morrice, N., & Tornqvist, H. E.
- Affiliations
- Novo Nordisk (Denmark) (DK)
- Wellcome Trust (GB)
- University of Dundee (GB)
- Corresponding author
- Jakobsen, Søren N.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-12
- Volume
- 276
- Issue
- 50
- Pages
- 46912-46916
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2041502315
- Cited by
- 238
- References
- 36
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 4 · 2018: 9 · 2017: 10 · 2016: 6 · 2015: 6 · 2014: 11 · 2013: 16 · 2012: 13
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- AMPK, IRS-1, AICAR, phosphatidylinositol 3-kinase, insulin signaling, skeletal muscle, C2C12 myotubes, physical activity, insulin sensitivity, type 2 diabetes, glucose transport
- MeSH terms
- Aminoimidazole Carboxamide, Animals, Binding Sites, Biological Transport, Cells, Cultured, Dose-Response Relationship, Drug, Electrophoresis, Polyacrylamide Gel, Enzyme Activation, Glucose, Humans, Insulin, Multienzyme Complexes, Myocardium, Peptides, Phosphoproteins, Phosphorylation, Protein Binding, Recombinant Proteins, Ribonucleosides, Serine, Subcellular Fractions, Time Factors, Blotting, Western, Signal Transduction, Protein Serine-Threonine Kinases, Muscle, Skeletal, Phosphatidylinositol 3-Kinases, Mice, AMP-Activated Protein Kinases, Insulin Receptor Substrate Proteins
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