ArticleAmerican journal of physiology. Endocrinology and metabolism2011
Feedback regulation of hepatic gluconeogenesis through modulation of SHP/Nr0b2 gene expression by Sirt1 and FoxO1.
Article in American journal of physiology. Endocrinology and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 51 citations in OpenAlex.
- Post-translational modifications in the pathophysiological process of metabolic dysfunction‑associated steatotic liver disease.Cell & bioscience · 2025Review
- Hepatic transcriptional responses to fasting and feeding.Genes & development · 2021Review
- Sirt1 coordinates with ERα to regulate autophagy and adiposity.Cell death discovery · 2021Article
- Review
- Loss of growth hormone-mediated signal transducer and activator of transcription 5 (STAT5) signaling in mice results in insulin sensitivity with obesity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Glucagon-Induced Acetylation of Energy-Sensing Factors in Control of Hepatic Metabolism.International journal of molecular sciences · 2019Review
- Global Analyses of Selective Insulin Resistance in Hepatocytes Caused by Palmitate Lipotoxicity.Molecular & cellular proteomics : MCP · 2018Article
- Gangliosides in Diabetic Wound Healing.Progress in molecular biology and translational science · 2018Review
- FOXO transcription factors protect against the diet-induced fatty liver disease.Scientific reports · 2017Article
- Interdependence of nutrient metabolism and the circadian clock system: Importance for metabolic health.Molecular metabolism · 2016Review
- Mathematical modelling of metabolic regulation in aging.Metabolites · 2015Review
- Ganglioside GM3 depletion reverses impaired wound healing in diabetic mice by activating IGF-1 and insulin receptors.The Journal of investigative dermatology · 2014Article
- Deleted in breast cancer 1 (DBC1) protein regulates hepatic gluconeogenesis.The Journal of biological chemistry · 2014Article
- Energy metabolism in the liver.Comprehensive Physiology · 2014Review
- Neuronal Sirt1 deficiency increases insulin sensitivity in both brain and peripheral tissues.The Journal of biological chemistry · 2013Article
- FOXO1/3 depletion in granulosa cells alters follicle growth, death and regulation of pituitary FSH.Molecular endocrinology (Baltimore, Md.) · 2013Article
- Article
- Genetic inactivation of pyruvate dehydrogenase kinases improves hepatic insulin resistance induced diabetes.PloS one · 2013Article
- A highly selective and potent PTP-MEG2 inhibitor with therapeutic potential for type 2 diabetes.Journal of the American Chemical Society · 2012Article
- Sirtuin biology and relevance to diabetes treatment.Diabetes management (London, England) · 2012Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Protein deacetylase Sirt1 has been implicated in the regulation of hepatic gluconeogenesis; however, the mechanisms are not fully understood. To further elucidate how Sirt1 regulates gluconeogenesis, we took a loss-of-function approach by deleting the coding DNA sequence for the catalytic domain of the Sirt1 gene in the liver of a wild-type mouse (LKO(Sirt)¹) or a genetic diabetic mouse in which hepatic insulin receptor substrates 1 and 2 are deleted (DKO(Irs½)). Whereas LKO(Sirt)¹ mice exhibited normal levels of fasting and fed blood glucose, inactivation of Sirt1 in DKO(Irs½) mice (TKO(Irs½:Sirt)¹) reduced blood glucose levels and moderately improved systemic glucose tolerance. Pyruvate tolerance was also significantly improved in TKO(Irs½:Sirt)¹ mice, suggesting that Sirt1 promotes hepatic gluconeogenesis in this diabetic mouse model. To understand why inactivation of hepatic Sirt1 does not alter blood glucose levels in the wild-type background, we searched for a potential cause and found that expression of small heterodimer partner (SHP, encoded by the Nr0b2 gene), an orphan nuclear receptor, which has been shown to suppress the activity of forkhead transcription factor FoxO1, was decreased in the liver of LKO(Sirt)¹ mice. Furthermore, our luciferase reporter assays and chromatin immunoprecipitation analysis revealed that the Nr0b2 gene is a target of FoxO1, which is also regulated by Sirt1. After the gene is upregulated, Nr0b2 can feed back and repress FoxO1- and Sirt1-activated G6pc and Pdk4 gene expression. Thus, our results suggest that Sirt1 can both positively and negatively regulate hepatic gluconeogenesis through FoxO1 and Nr0b2 and keep this physiological process in control.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.