ArticleThe Biochemical journal2003
Analysis of the role of protein kinase B (cAKT) in insulin-dependent induction of glucokinase and sterol regulatory element-binding protein 1 (SREBP1) mRNAs in hepatocytes.
Article in The Biochemical journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 60 citations in OpenAlex.
- Circulating Sphingolipids and Glucose Homeostasis: An Update.International journal of molecular sciences · 2023Review
- Maintenance of liver glycogen during long-term fasting preserves energy state in mice.FEBS letters · 2020Article
- Sphingolipids in Non-Alcoholic Fatty Liver Disease and Hepatocellular Carcinoma: Ceramide Turnover.International journal of molecular sciences · 2019Review
- The unfolded protein response and hepatic lipid metabolism in non alcoholic fatty liver disease.Pharmacology & therapeutics · 2019Review
- Article
- Higher protein kinase C ζ in fatty rat liver and its effect on insulin actions in primary hepatocytes.PloS one · 2015Article
- The selective control of glycolysis, gluconeogenesis and glycogenesis by temporal insulin patterns.Molecular systems biology · 2013Article
- Adenovirus-mediated overexpression of Tcfe3 ameliorates hyperglycaemia in a mouse model of diabetes by upregulating glucokinase in the liver.Diabetologia · 2013Article
- Role of ceramides in nonalcoholic fatty liver disease.Trends in endocrinology and metabolism: TEM · 2012Article
- Insulin enhances post-translational processing of nascent SREBP-1c by promoting its phosphorylation and association with COPII vesicles.The Journal of biological chemistry · 2009Article
- Molecular physiology of mammalian glucokinase.Cellular and molecular life sciences : CMLS · 2009Review
- N-3 polyunsaturated fatty acid regulation of hepatic gene transcription.Current opinion in lipidology · 2008Review
- Docosahexaenoic acid (DHA) and hepatic gene transcription.Chemistry and physics of lipids · 2008Review
- Cholesterol: from feeding to gene regulation.Genes & nutrition · 2007Article
- Insulin induction of glucokinase and fatty acid synthase in hepatocytes: analysis of the roles of sterol-regulatory-element-binding protein-1c and liver X receptor.The Biochemical journal · 2006Article
- Signalling mechanisms linking hepatic glucose and lipid metabolism.Diabetologia · 2006Review
- Docosahexaneoic acid (22:6,n-3) regulates rat hepatocyte SREBP-1 nuclear abundance by Erk- and 26S proteasome-dependent pathways.Journal of lipid research · 2006Article
- The role of protein kinase B/Akt in insulin-induced inactivation of phosphorylase in rat hepatocytes.Diabetologia · 2006Article
- Lack of evidence for a role of TRB3/NIPK as an inhibitor of PKB-mediated insulin signalling in primary hepatocytes.The Biochemical journal · 2005Article
- Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure.The Biochemical journal · 2005Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous work showed that acute stimulation of a conditionally active protein kinase B (PKB or cAKT) was sufficient to elicit insulin-like induction of GCK (glucokinase) and SREBP1 (sterol regulatory element-binding protein 1) in hepatocytes [Iynedjian, Roth, Fleischmann and Gjinovci (2000) Biochem. J. 351, 621-627; Fleischmann and Iynedjian (2000) Biochem. J. 349, 13-17]. The objective of the present study was to determine whether activation of PKB during insulin stimulation of hepatocytes was a necessary condition for the induction of the two genes. Activation of PKB by insulin was inhibited by pretreatment of the hepatocytes with C2 ceramide. This resulted in the inhibition of insulin-dependent increases in GCK and SREBP1 mRNAs. A triple mutant of PKB failed to interfere with insulin activation of PKB in hepatocytes even at high overexpression levels achieved after adenovirus transduction. A PKB-CaaX fusion protein, which can act as a dominant-negative inhibitor of PKB activation in other cells, was shown to be constitutively activated in hepatocytes and to trigger insulin-like induction of GCK and SREBP1. In addition, constitutive PKB-CaaX activity caused refractoriness of the hepatocytes to insulin signalling at an upstream step resulting in the inhibition of both extracellular-signal-regulated kinase 1/2 and endogenous PKB activation. The stimulation of gene expression by constitutively active PKB-CaaX and inhibition of the insulin effect by ceramide are compatible with a role for PKB in the insulin-dependent induction of GCK and SREBP1.
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