ArticleProceedings of the National Academy of Sciences of the United States of America1999
Sterol regulatory element binding protein-1c is a major mediator of insulin action on the hepatic expression of glucokinase and lipogenesis-related genes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 219 papers.
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219 citing papers in PubMed, 733 citations in OpenAlex.
- Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease.The Journal of clinical investigation · 2020Trial
- The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans.The Journal of clinical investigation · 2012Trial
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- Constitutive androstane receptor, liver pathophysiology and chemical contaminants: current evidence and perspectives.Frontiers in endocrinology · 2025Review
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- Morning Engagement of Hepatic Insulin Receptors Improves Afternoon Hepatic Glucose Disposal and Storage.bioRxiv : the preprint server for biology · 2024Article
- Some paradoxes and unresolved aspects of hepatic de novo lipogenesis.npj metabolic health and disease · 2024Review
- Regulation and targeting of SREBP-1 in hepatocellular carcinoma.Cancer metastasis reviews · 2024Review
- Secretin-dependent signals in the ventromedial hypothalamus regulate energy metabolism and bone homeostasis in mice.Nature communications · 2024Article
- mTORC1 controls murine postprandial hepatic glycogen synthesis via Ppp1r3b.The Journal of clinical investigation · 2024Article
159 more citing papers are in PubMed but not listed here.
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4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatic glucokinase plays a key role in glucose metabolism as underlined by the anomalies associated with glucokinase mutations and the consequences of tissue-specific knock-out. In the liver, glucokinase transcription is absolutely dependent on the presence of insulin. The cis-elements and trans-acting factors that mediate the insulin effect are presently unknown; this is also the case for most insulin-responsive genes. We have shown previously that the hepatic expression of the transcription factor sterol regulatory element binding protein-1c (SREBP-1c) is activated by insulin. We show here in primary cultures of hepatocytes that the adenovirus-mediated transduction of a dominant negative form of SREBP-1c inhibits the insulin effect on endogenous glucokinase expression. Conversely, in the absence of insulin, the adenovirus-mediated transduction of a dominant positive form of SREBP-1c overcomes the insulin dependency of glucokinase expression. Hepatic fatty acid synthase and Spot-14 are insulin/glucose-dependent genes. For this latter class of genes, the dominant positive form of SREBP-1c obviates the necessity for the presence of insulin, whereas glucose potentiates the effect of SREBP-1c on their expression. In addition, the insulin dependency of lipid accumulation in cultured hepatocytes is overcome by the dominant positive form of SREBP-1c. We propose that SREBP-1c is a major mediator of insulin action on hepatic gene expression and a key regulator of hepatic glucose/lipid metabolism.
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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.