ArticleThe Biochemical journal2005
Lack of evidence for a role of TRB3/NIPK as an inhibitor of PKB-mediated insulin signalling in primary hepatocytes.
Article in The Biochemical journal, 2005. 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, 58 citations in OpenAlex.
- Effects ofFrontiers in veterinary science · 2026Article
- Endoplasmic reticulum proteostasis in hepatic steatosis.Nature reviews. Endocrinology · 2016Review
- Regulation of hepatic TRB3/Akt interaction induced by physical exercise and its effect on the hepatic glucose production in an insulin resistance state.Diabetology & metabolic syndrome · 2015Article
- Drosophila tribbles antagonizes insulin signaling-mediated growth and metabolism via interactions with Akt kinase.PloS one · 2014Article
- TRB3 is involved in free fatty acid-induced INS-1-derived cell apoptosis via the protein kinase C δ pathway.PloS one · 2014Article
- Article
- Mammalian tribbles homologs at the crossroads of endoplasmic reticulum stress and Mammalian target of rapamycin pathways.Scientifica · 2013Article
- Carbohydrate metabolism is perturbed in peroxisome-deficient hepatocytes due to mitochondrial dysfunction, AMP-activated protein kinase (AMPK) activation, and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) suppression.The Journal of biological chemistry · 2011Article
- Article
- Tribbles homologue 3 (TRIB3) and the insulin-resistance genes in type 2 diabetes.Diabetologia · 2010Article
- Aberrant hepatic TRIB3 gene expression in insulin-resistant obese humans.Diabetologia · 2010Article
- Mammalian Tribbles homolog 3 impairs insulin action in skeletal muscle: role in glucose-induced insulin resistance.American journal of physiology. Endocrinology and metabolism · 2010Article
- Insulin signaling regulating genes: effect on T2DM and cardiovascular risk.Nature reviews. Endocrinology · 2009Review
- The small molecule phenamil induces osteoblast differentiation and mineralization.Molecular and cellular biology · 2009Article
- Postreceptoral adipocyte insulin resistance induced by nelfinavir is caused by insensitivity of PKB/Akt to phosphatidylinositol-3,4,5-trisphosphate.Endocrinology · 2009Article
- Association of TRB3 gene Q84R polymorphism with type 2 diabetes mellitus in Chinese population.Endocrine · 2009Article
- Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells.The Journal of clinical investigation · 2009Article
- Increased expression of the Akt/PKB inhibitor TRB3 in osteoarthritic chondrocytes inhibits insulin-like growth factor 1-mediated cell survival and proteoglycan synthesis.Arthritis and rheumatism · 2009Article
- Molecular physiology of mammalian glucokinase.Cellular and molecular life sciences : CMLS · 2009Review
- Paradoxical effects of increased expression of PGC-1alpha on muscle mitochondrial function and insulin-stimulated muscle glucose metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The protein TRB3 (tribbles 3), also called NIPK (neuronal cell death-inducible protein kinase), was recently identified as a protein-protein interaction partner and an inhibitor of PKB (protein kinase B). To explore the hypothesis that TRB3/NIPK might act as a negative regulator of insulin signalling in the liver, this protein was overexpressed by adenoviral transduction of primary cultures of rat hepatocytes, and various aspects of insulin action were investigated. The insulin-induced phosphorylation of Ser-473 and Thr-308 of PKB was found to be undiminished in transduced hepatocytes with a molar excess of TRB3/NIPK over PKB of more than 25-fold. Consistent with unimpaired insulin activation of PKB, the stimulation of Ser-21 and Ser-9 phosphorylation of glycogen synthase kinase 3-alpha and -beta, and the apparent phosphorylation level of 4E-BP1 (eukaryotic initiation factor 4-binding protein 1), were similar in transduced and control hepatocytes. The induction by insulin of the mRNAs encoding glucokinase and SREBF1 (sterol-regulatory-element-binding factor 1) were also normal in TRB3/NIPK hepatocytes. In contrast, the insulin-dependent induction of these two genes, as well as the activation of PKB, were shown to be suppressed in hepatocytes treated with the lipid ether compound PIA6 (phosphatidylinositol ether lipid analogue 6), a recently discovered specific inhibitor of PKB. Since TRB3/NIPK was reported to be increased in the liver of fasting mice, the effects of glucagon, glucocorticoids and insulin on the level of endogenous TRB3/NIPK mRNA in primary hepatocytes were investigated. No significant change in mRNA level occurred under any of the hormonal treatments. The present study does not support the hypothesis that the physiological role of TRB3/NIPK might be to put a brake on insulin signalling in hepatocytes.
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