ArticleDiabetes2016
4E-BP2/SH2B1/IRS2 Are Part of a Novel Feedback Loop That Controls β-Cell Mass.
Article in Diabetes, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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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
12 citing papers in PubMed, 14 citations in OpenAlex.
- Article
- SH2B1 Tunes Hippocampal ERK Signaling to Influence Fluid Intelligence in Humans and Mice.Research (Washington, D.C.) · 2023Article
- The Wnt signaling receptor Fzd9 is essential for Myc-driven tumorigenesis in pancreatic islets.Life science alliance · 2021Article
- The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass.Scientific reports · 2021Article
- Translational Factor eIF4G1 Regulates Glucose Homeostasis and Pancreatic β-Cell Function.Diabetes · 2021Article
- Causal association between mTOR-dependent EIF-4E and EIF-4A circulating protein levels and type 2 diabetes: a Mendelian randomization study.Scientific reports · 2020Article
- SH2B1 protects against OGD/R‑induced apoptosis in PC12 cells via activation of the JAK2/STAT3 signaling pathway.Molecular medicine reports · 2018Article
- SH2B1 promotes epithelial-mesenchymal transition through the IRS1/β-catenin signaling axis in lung adenocarcinoma.Molecular carcinogenesis · 2018Article
- Emerging roles of RNA-binding proteins in diabetes and their therapeutic potential in diabetic complications.Wiley interdisciplinary reviews. RNA · 2018Review
- SH2B1 promotes NSCLC cell proliferation through PI3K/Akt/mTOR signaling cascade.Cancer cell international · 2018Article
- Loss of mTORC1 signalling impairs β-cell homeostasis and insulin processing.Nature communications · 2017Article
- Circulating microRNA (miRNA) Expression Profiling in Plasma of Patients with Gestational Diabetes Mellitus Reveals Upregulation of miRNA miR-330-3p.Frontiers in endocrinology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The mammalian target of rapamycin complex 1 (mTORC1) regulates several biological processes, although the key downstream mechanisms responsible for these effects are poorly defined. Using mice with deletion of eukaryotic translation initiation factor 4E-binding protein 2 (4E-BP2), we determine that this downstream target is a major regulator of glucose homeostasis and β-cell mass, proliferation, and survival by increasing insulin receptor substrate 2 (IRS2) levels and identify a novel feedback mechanism by which mTORC1 signaling increases IRS2 levels. In this feedback loop, we show that 4E-BP2 deletion induces translation of the adaptor protein SH2B1 and promotes the formation of a complex with IRS2 and Janus kinase 2, preventing IRS2 ubiquitination. The changes in IRS2 levels result in increases in cell cycle progression, cell survival, and β-cell mass by increasing Akt signaling and reducing p27 levels. Importantly, 4E-BP2 deletion confers resistance to cytokine treatment in vitro. Our data identify SH2B1 as a major regulator of IRS2 stability, demonstrate a novel feedback mechanism linking mTORC1 signaling with IRS2, and identify 4E-BP2 as a major regulator of proliferation and survival of β-cells.
Indexed as
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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.