ArticleDiabetes2014
Epidermal growth factor receptor signaling promotes pancreatic β-cell proliferation in response to nutrient excess in rats through mTOR and FOXM1.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
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- Single-cell RNA sequencing identifies endothelial-derived HBEGF as promoting pancreatic beta cell proliferation in mice via the EGFR-Kmt5a-H4K20me pathway.Diabetologia · 2025Article
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- Transcriptomic heterogeneity of non-beta islet cells is associated with type 2 diabetes development in mouse models.Diabetologia · 2025Article
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- Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity.Experimental & molecular medicine · 2024Review
- Role of transcription factor FOXM1 in diabetes and its complications (Review).International journal of molecular medicine · 2023Article
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- FOXM1: Functional Roles of FOXM1 in Non-Malignant Diseases.Biomolecules · 2023Review
- Glucolipotoxic Stress-Induced Mig6 Desensitizes EGFR Signaling and Promotes Pancreatic Beta Cell Death.Metabolites · 2023Article
- Pancreatic loss of Mig6 alters murine endocrine cell fate and protects functional beta cell mass in an STZ-induced model of diabetes.bioRxiv : the preprint server for biology · 2023Article
- β Cell mass expansion during puberty involves serotonin signaling and determines glucose homeostasis in adulthood.JCI insight · 2022Article
- Very-Long-Chain Unsaturated Sphingolipids Mediate Oleate-Induced Rat β-Cell Proliferation.Diabetes · 2022Article
- Molecular study of the proliferation process of beta cells derived from pluripotent stem cells.Molecular biology reports · 2022Review
- Adaptive Changes in Glucose Homeostasis and Islet Function During Pregnancy: A Targeted Metabolomics Study in Mice.Frontiers in endocrinology · 2022Article
- Article
- Transcriptomic and Quantitative Proteomic Profiling Reveals Signaling Pathways Critical for Pancreatic Islet Maturation.Endocrinology · 2020Article
- HB-EGF Signaling Is Required for Glucose-Induced Pancreatic β-Cell Proliferation in Rats.Diabetes · 2020Article
- Myc Is Required for Adaptive β-Cell Replication in Young Mice but Is Not Sufficient in One-Year-Old Mice Fed With a High-Fat Diet.Diabetes · 2019Article
- The autonomic nervous system regulates pancreatic β-cell proliferation in adult male rats.American journal of physiology. Endocrinology and metabolism · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The cellular and molecular mechanisms underpinning the compensatory increase in β-cell mass in response to insulin resistance are essentially unknown. We previously reported that a 72-h coinfusion of glucose and Intralipid (GLU+IL) induces insulin resistance and a marked increase in β-cell proliferation in 6-month-old, but not in 2-month-old, Wistar rats. The aim of the current study was to identify the mechanisms underlying nutrient-induced β-cell proliferation in this model. A transcriptomic analysis identified a central role for the forkhead transcription factor FOXM1 and its targets, and for heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), a ligand of the EGF receptor (EGFR), in nutrient-induced β-cell proliferation. Phosphorylation of ribosomal S6 kinase, a mammalian target of rapamycin (mTOR) target, was increased in islets from GLU+IL-infused 6-month-old rats. HB-EGF induced proliferation of insulin-secreting MIN6 cells and isolated rat islets, and this effect was blocked in MIN6 cells by the EGFR inhibitor AG1478 or the mTOR inhibitor rapamycin. Coinfusion of either AG1478 or rapamycin blocked the increase in FOXM1 signaling, β-cell proliferation, and β-cell mass and size in response to GLU+IL infusion in 6-month-old rats. We conclude that chronic nutrient excess promotes β-cell mass expansion via a pathway that involves EGFR signaling, mTOR activation, and FOXM1-mediated cell proliferation.
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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.