The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Metformin and Insulin Suppress Hepatic Gluconeogenesis through Phosphorylation of CREB Binding Protein
Open accessAbstract
SUMMARY Insulin resistance and elevated glucagon levels result in non-suppressible hepatic glucose production and hyperglycemia in patients with type 2 diabetes. The CREB co-activator complex controls transcription of hepatic gluconeogenic enzyme genes. Here we show that both the antidiabetic agent metformin and insulin phosphorylate the transcriptional co-activator CBP at serine 436 via PKCι/λ. This event triggers the dissociation of the CREB-CBP-TORC2 transcription complex and reduces gluconeogenic enzyme gene expression. Mice carrying a germline mutation of this CBP phosphorylation site (S436A) demonstrate resistance to the hypoglycemic effect of both insulin and metformin. Obese, hyperglycemic mice display hepatic insulin resistance, but metformin is still effective in treating the hyperglycemia of these mice since it stimulates CBP phosphorylation by bypassing the block in insulin signaling.
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Cites
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Cited by
Cellular and molecular mechanisms of metformin: an overview
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Metformin: from mechanisms of action to therapies
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Metformin improves healthspan and lifespan in mice
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Metadata
- Authors
- He, L., Sabet, A., Djedjos, S., Miller, R., Sun, X., Hussain, M. A., Radovick, S., & Wondisford, F. E.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 137
- Issue
- 4
- Pages
- 635-646
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2000047954
- Cited by
- 481
- References
- 31
- FWCI
- 11.64
- Type
- journal article
- Language
- en
- Open access
- bronze
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- He, L., Sabet, A., Djedjos, S., Miller, R., Sun, X., Hussain, M. A., Radovick, S., & Wondisford, F. E. (2009). Metformin and Insulin Suppress Hepatic Gluconeogenesis through Phosphorylation of CREB Binding Protein. Cell. https://doi.org/10.1016/j.cell.2009.03.016
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