ArticleThe Journal of clinical investigation2010
The pseudokinase tribbles homolog 3 interacts with ATF4 to negatively regulate insulin exocytosis in human and mouse beta cells.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 85 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
85 citing papers in PubMed, 125 citations in OpenAlex.
- TRIB3 Links Endoplasmic Reticulum Stress to Impaired Efferocytosis in Atherosclerosis.Circulation research · 2025Article
- Characteristics of Berberine Effects on Insulin Exocytosis in Pancreatic β Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Article
- Unraveling the Mystery of Insulin Resistance: From Principle Mechanistic Insights and Consequences to Therapeutic Interventions.International journal of molecular sciences · 2025Review
- Diet-induced obesity and aging-induced upregulation of Trib3 interfere with energy homeostasis by downregulating the thermogenic capacity of BAT.Experimental & molecular medicine · 2024Article
- Comprehensive pan-cancer analysis unveils the significant prognostic value and potential role in immune microenvironment modulation of TRIB3.Computational and structural biotechnology journal · 2024Article
- Association between protein undernutrition and diabetes: Molecular implications in the reduction of insulin secretion.Reviews in endocrine & metabolic disorders · 2024Review
- Integration of dietary nutrition and TRIB3 action into diabetes mellitus.Nutrition reviews · 2024Review
- Activation of brown adipose tissue by a low-protein diet ameliorates hyperglycemia in a diabetic lipodystrophy mouse model.Scientific reports · 2023Article
- Pancreatic islet protection at the expense of secretory function involves serine-linked mitochondrial one-carbon metabolism.Cell reports · 2023Article
- Review
- Upregulation of Tribbles decreases body weight and increases sleep duration.Disease models & mechanisms · 2023Article
- Activation of brown adipose tissue by a low-protein diet ameliorates hyperglycemia in a diabetic lipodystrophy mouse model.Research square · 2023Article
- TRIB3 Mediates Fibroblast Activation and Fibrosis though Interaction with ATF4 in IPF.International journal of molecular sciences · 2022Article
- ROCK1 regulates insulin secretion from β-cells.Molecular metabolism · 2022Article
- Secreted EMC10 is upregulated in human obesity and its neutralizing antibody prevents diet-induced obesity in mice.Nature communications · 2022Article
- Serine biosynthesis as a novel therapeutic target for dilated cardiomyopathy.European heart journal · 2022Article
- Increased expression of tribbles homolog 3 predicts poor prognosis and correlates with tumor immunity in clear cell renal cell carcinoma: a bioinformatics study.Bioengineered · 2022Article
- Ginseng Pectin WGPA Alleviates Exercise-Induced Fatigue by Enhancing Gluconeogenesis.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Hypercholesterolemia Impairs Clearance of Neutrophil Extracellular Traps and Promotes Inflammation and Atherosclerotic Plaque Progression.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
- Expression of concern
Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Insufficient insulin secretion and reduced pancreatic beta cell mass are hallmarks of type 2 diabetes (T2DM). Here, we confirm that a previously identified polymorphism (rs2295490/Q84R) in exon 2 of the pseudokinase-encoding gene tribbles 3 (TRB3) is associated with an increased risk for T2DM in 2 populations of people of mixed European descent. Carriers of the 84R allele had substantially reduced plasma levels of C-peptide, the product of proinsulin processing to insulin, suggesting a role for TRB3 in beta cell function. Overexpression of TRB3 84R in mouse beta cells, human islet cells, and the murine beta cell line MIN6 revealed reduced insulin exocytosis, associated with a marked reduction in docked insulin granules visualized by electron microscopy. Conversely, knockdown of TRB3 in MIN6 cells restored insulin secretion and expression of exocytosis genes. Further analysis in MIN6 cells demonstrated that TRB3 interacted with the transcription factor ATF4 and that this complex acted as a competitive inhibitor of cAMP response element-binding (CREB) transcription factor in the regulation of key exocytosis genes. In addition, the 84R TRB3 variant exhibited greater protein stability than wild-type TRB3 and increased binding affinity to Akt. Mice overexpressing TRB3 84R in beta cells displayed decreased beta cell mass, associated with reduced proliferation and enhanced apoptosis rates. These data link a missense polymorphism in human TRB3 to impaired insulin exocytosis and thus increased risk for T2DM.
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.