ArticleDiabetologia2010
Aberrant hepatic TRIB3 gene expression in insulin-resistant obese humans.
Article in Diabetologia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Transcriptomic responses and molecular mechanisms of glucagon-regulated glucose metabolism in Japanese flounder (Frontiers in physiology · 2026Article
- Aberrant activation of p53-TRIB3 axis contributes to diabetic myocardial insulin resistance and sulforaphane protection.Journal of advanced research · 2025Article
- Integration of dietary nutrition and TRIB3 action into diabetes mellitus.Nutrition reviews · 2024Review
- Delayed Gut Colonization Changes Future Insulin Resistance and Hepatic Gene Expression but Not Adiposity in Obese Mice.Journal of obesity · 2024Article
- Involvement of Lipophagy and Chaperone-Mediated Autophagy in the Pathogenesis of Non-Alcoholic Fatty Liver Disease by Regulation of Lipid Droplets.International journal of molecular sciences · 2023Review
- Upregulation of Tribbles decreases body weight and increases sleep duration.Disease models & mechanisms · 2023Article
- Circulating TRB3 and GRP78 levels in type 2 diabetes patients: crosstalk between glucose homeostasis and endoplasmic reticulum stress.Journal of endocrinological investigation · 2022Article
- TRAF6 Suppresses the Development of Pulmonary Fibrosis by Attenuating the Activation of Fibroblasts.Frontiers in pharmacology · 2022Article
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- New Insights Into the Role of Autophagy in Liver Surgery in the Setting of Metabolic Syndrome and Related Diseases.Frontiers in cell and developmental biology · 2021Review
- Capsaicin Targets Lipogenesis in HepG2 Cells Through AMPK Activation, AKT Inhibition and PPARs Regulation.International journal of molecular sciences · 2019Article
- Metabolic aspects in NAFLD, NASH and hepatocellular carcinoma: the role of PGC1 coactivators.Nature reviews. Gastroenterology & hepatology · 2019Review
- ADisease models & mechanisms · 2017Article
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- Acute vs chronic exposure to high fat diet leads to distinct regulation of PKA.Journal of molecular endocrinology · 2017Article
- Hemeoxygenase-1 as a Novel Driver in Ritonavir-Induced Insulin Resistance in HIV-1-Infected Patients.Journal of acquired immune deficiency syndromes (1999) · 2017Article
- Cellular and Molecular Mechanisms of Diabetic Atherosclerosis: Herbal Medicines as a Potential Therapeutic Approach.Oxidative medicine and cellular longevity · 2017Review
- Endoplasmic reticulum proteostasis in hepatic steatosis.Nature reviews. Endocrinology · 2016Review
- High fat diet-induced TGF-β/Gbb signaling provokes insulin resistance through the tribbles expression.Scientific reports · 2016Article
- Skeletal muscle atrogene expression and insulin resistance in a rat model of polytrauma.Physiological reports · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
aims/hypothesisThe pseudokinase tribbles homologue 3 (Drosophila) (TRIB3) negatively interferes with insulin-mediated phosphorylation and activation of v-akt murine thymoma viral oncogene homologue 1 (AKT1, also known as protein kinase B). Animal studies have shown that Trib3 expression was higher in the fasting state and in animal models of diabetes, promoting hyperglycaemia presumably by increasing glucose production in the liver. Less is known about the role of TRIB3 in insulin resistance in humans, although a gain-of-function mutation associated with abnormalities related to insulin resistance has been described in TRIB3.
methodsWe determined hepatic mRNA expression of TRIB3 and selected genes encoding enzymes, transcription factors and coactivators involved in glucose homeostasis. We also determined biochemical variables of intermediary metabolism in obese patients with varying degrees of insulin resistance.
resultsIn our study population hepatic TRIB3 mRNA expression was associated with surrogate markers of insulin resistance. TRIB3 expression was significantly increased in a subgroup with high HOMA of insulin resistance (HOMA-IR) compared with a low HOMA-IR group (p = 0.0033). TRIB3 transcript levels were correlated with PEPCK (also known as PCK2) mRNA expression (p = 0.0014) and mRNA expression of PPARGC1A (p = 0.0020), PPARGC1B (p < 0.0001), USF1 (p = 0.0017), FOXO1 (p = 0.0003) and SREBP-1c (also known as SREBF1; p = 0.0360). Furthermore ligands of peroxisome proliferator-activated receptor alpha/retinoid X receptor and overexpression of its coactivator PPARGC1A as well as overexpression of SREBP-1c and its coactivator PPARGC1B increased TRIB3 promoter activity in HepG2 cells. CONCLUSIONS/
interpretationWe have found evidence for a role of aberrant hepatic TRIB3 transcript levels in insulin resistance in obese humans and identified potential transcriptional pathways involved in regulation of TRIB3 gene expression in the liver.
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