ArticleThe Biochemical journal2005
Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure.
Article in The Biochemical journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 91 citations in OpenAlex.
- 3-Phosphoinositide-Dependent Kinase 1 as a Therapeutic Target for Treating Diabetes.Current diabetes reviews · 2025Review
- The Pathogenesis of Diabetes.International journal of molecular sciences · 2023Review
- A novel small molecule, CU05-1189, targeting the pleckstrin homology domain of PDK1 suppresses VEGF-mediated angiogenesis and tumor growth by blocking the Akt signaling pathway.Frontiers in pharmacology · 2023Article
- Molecular programming modulates hepatic lipid metabolism and adult metabolic risk in the offspring of obese mothers in a sex-specific manner.Communications biology · 2022Article
- Review
- mTORC2 Facilitates Liver Regeneration Through Sphingolipid-Induced PPAR-α-Fatty Acid Oxidation.Cellular and molecular gastroenterology and hepatology · 2022Article
- Article
- Role of Insulin Resistance in MAFLD.International journal of molecular sciences · 2021Review
- Serine 474 phosphorylation is essential for maximal Akt2 kinase activity in adipocytes.The Journal of biological chemistry · 2019Article
- MicroRNAs in the Migration of Mesenchymal Stem Cells.Stem cell reviews and reports · 2019Review
- Resolving the Paradox of Hepatic Insulin Resistance.Cellular and molecular gastroenterology and hepatology · 2019Review
- Insulin regulation of gluconeogenesis.Annals of the New York Academy of Sciences · 2018Review
- Targeting PDK1 for Chemosensitization of Cancer Cells.Cancers · 2017Review
- p38γ and p38δ reprogram liver metabolism by modulating neutrophil infiltration.The EMBO journal · 2016Article
- Impact of maternal undernutrition around the time of conception on factors regulating hepatic lipid metabolism and microRNAs in singleton and twin fetuses.American journal of physiology. Endocrinology and metabolism · 2016Article
- mTORC1-independent Raptor prevents hepatic steatosis by stabilizing PHLPP2.Nature communications · 2016Article
- PI3K-C2γ is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling.Nature communications · 2015Article
- Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo.Molecular metabolism · 2014Article
- Insulin signaling, resistance, and the metabolic syndrome: insights from mouse models into disease mechanisms.The Journal of endocrinology · 2014Review
- Activated α2-macroglobulin binding to cell surface GRP78 induces T-loop phosphorylation of Akt1 by PDK1 in association with Raptor.PloS one · 2014Article
Corrections and comments
- Retraction · 2024-07-26Duplication of/in Image · Investigation by Third Party ·
- Retracted
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The liver plays an important role in insulin-regulated glucose homoeostasis. To study the function of the PDK1 (3-phosphoinositide-dependent protein kinase-1) signalling pathway in mediating insulin's actions in the liver, we employed CRE recombinase/loxP technology to generate L(liver)-PDK1-/- mice, which lack expression of PDK1 in hepatocytes and in which insulin failed to induce activation of PKB in liver. The L-PDK1-/- mice were not insulin-intolerant, possessed normal levels of blood glucose and insulin under normal feeding conditions, but were markedly glucose-intolerant when injected with glucose. The L-PDK1-/- mice also possessed 10-fold lower levels of hepatic glycogen compared with control littermates, and were unable to normalize their blood glucose levels within 2 h after injection of insulin. The glucose intolerance of the L-PDK1-/- mice may be due to an inability of glucose to suppress hepatic glucose output through the gluconeogenic pathway, since the mRNA encoding hepatic PEPCK (phosphoenolpyruvate carboxykinase), G6Pase (glucose-6-phosphatase) and SREBP1 (sterol-regulatory-element-binding protein 1), which regulate gluconeogenesis, are no longer controlled by feeding. Furthermore, three other insulin-controlled genes, namely IGFBP1 (insulin-like-growth-factor-binding protein-1), IRS2 (insulin receptor substrate 2) and glucokinase, were regulated abnormally by feeding in the liver of PDK1-deficient mice. Finally, the L-PDK1-/- mice died between 4-16 weeks of age due to liver failure. These results establish that the PDK1 signalling pathway plays an important role in regulating glucose homoeostasis and controlling expression of insulin-regulated genes. They suggest that a deficiency of the PDK1 pathway in the liver could contribute to development of diabetes, as well as to liver failure.
Indexed as
Identifiers
What OpenQuestion holds
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.