ArticleThe Journal of clinical investigation2003
PKClambda in liver mediates insulin-induced SREBP-1c expression and determines both hepatic lipid content and overall insulin sensitivity.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 173 citations in OpenAlex.
- Metformin improves atypical protein kinase C activation by insulin and phosphatidylinositol-3,4,5-(PO4)3 in muscle of diabetic subjects.Diabetologia · 2006Trial
- Physiological and pathophysiological actions of insulin in the liver.Endocrine journal · 2025Review
- The Role of Acyl-CoA Synthetase 1 in Bioactive Lipid Accumulation and the Development of Hepatic Insulin Resistance.Nutrients · 2024Article
- Downregulation of PRKCI inhibits osteosarcoma cell growth by inactivating the Akt/mTOR signaling pathway.Frontiers in oncology · 2024Article
- Effects of Perilla Seed Meal on Productive Performance, Egg Quality, Antioxidant Capacity and Hepatic Lipid Metabolism of Wenchang Breeder Hens.Animals : an open access journal from MDPI · 2023Article
- Hepatic FASN deficiency differentially affects nonalcoholic fatty liver disease and diabetes in mouse obesity models.JCI insight · 2023Article
- Protein Phosphatase 2A as a Therapeutic Target in Pulmonary Diseases.Medicina (Kaunas, Lithuania) · 2023Review
- Potential role of microRNAs in selective hepatic insulin resistance: From paradox to the paradigm.Frontiers in endocrinology · 2022Review
- A network-based approach to identify protein kinases critical for regulating srebf1 in lipid deposition causing obesity.Functional & integrative genomics · 2021Article
- Hepatic transcriptional responses to fasting and feeding.Genes & development · 2021Review
- Review
- Larval nutrition influences adult fat stores and starvation resistance in Drosophila.PloS one · 2021Article
- Predicting the Probability that a Chemical Causes Steatosis Using Adverse Outcome Pathway Bayesian Networks (AOPBNs).Risk analysis : an official publication of the Society for Risk Analysis · 2020Article
- Transplantation of neuregulin 4-overexpressing adipose-derived mesenchymal stem cells ameliorates insulin resistance by attenuating hepatic steatosis.Experimental biology and medicine (Maywood, N.J.) · 2019Article
- PKCζ Phosphorylates SIRT6 to Mediate Fatty Acid β-Oxidation in Colon Cancer Cells.Neoplasia (New York, N.Y.) · 2019Article
- PHD3 regulates glucose metabolism by suppressing stress-induced signalling and optimising gluconeogenesis and insulin signalling in hepatocytes.Scientific reports · 2018Article
- SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.Nature reviews. Endocrinology · 2017Review
- A mathematical model of the impact of insulin secretion dynamics on selective hepatic insulin resistance.Nature communications · 2017Article
- Asymmetric division of contractile domains couples cell positioning and fate specification.Nature · 2016Article
- MeCP2 co-ordinates liver lipid metabolism with the NCoR1/HDAC3 corepressor complex.Human molecular genetics · 2016Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PKClambda is implicated as a downstream effector of PI3K in insulin action. We show here that mice that lack PKClambda specifically in the liver (L-lambdaKO mice), produced with the use of the Cre-loxP system, exhibit increased insulin sensitivity as well as a decreased triglyceride content and reduced expression of the sterol regulatory element-binding protein-1c (SREBP-1c) gene in the liver. Induction of the hepatic expression of Srebp1c and of its target genes involved in fatty acid/triglyceride synthesis by fasting and refeeding or by hepatic expression of an active form of PI3K was inhibited in L-lambdaKO mice compared with that in control animals. Expression of Srebp1c induced by insulin or by active PI3K in primary cultured rat hepatocytes was inhibited by a dominant-negative form of PKClambda and was mimicked by overexpression of WT PKClambda. Restoration of PKClambda expression in the liver of L-lambdaKO mice with the use of adenovirus-mediated gene transfer corrected the metabolic abnormalities of these animals. Hepatic PKClambda is thus a determinant of hepatic lipid content and whole-body insulin sensitivity.
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Registered trials
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.