ArticleThe Journal of biological chemistry2014
Glutamine stimulates biosynthesis and secretion of insulin-like growth factor 2 (IGF2), an autocrine regulator of beta cell mass and function.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Stem cell control and cancer initiation by an autocrine, injury-activated Igf complex.bioRxiv : the preprint server for biology · 2026Article
- Placental mTOR signalling links mitochondrial dysfunction, nutrient transport and neonatal beta cell perturbations in mice.Diabetologia · 2025Article
- Diabetes-preventive molecular mechanisms of breast versus formula feeding: new insights into the impact of milk on stem cell Wnt signaling.Frontiers in nutrition · 2025Review
- Review
- Therapeutic Strategies for Pancreatic-Cancer-Related Type 2 Diabetes Centered around Natural Products.International journal of molecular sciences · 2023Review
- Characterization of the Secretome, Transcriptome, and Proteome of Human β Cell Line EndoC-βH1.Molecular & cellular proteomics : MCP · 2022Article
- Glutamate is an essential mediator in glutamine-amplified insulin secretion.Journal of diabetes investigation · 2021Article
- Debates in Pancreatic Beta Cell Biology: Proliferation Versus Progenitor Differentiation and Transdifferentiation in Restoring β Cell Mass.Frontiers in endocrinology · 2021Review
- Integrin and autocrine IGF2 pathways control fasting insulin secretion in β-cells.The Journal of biological chemistry · 2020Article
- Article
- Short-Term Diet Induced Changes in the Central and Circulating IGF Systems Are Sex Specific.Frontiers in endocrinology · 2020Article
- Interplay Between Diabetes and Pancreatic Ductal Adenocarcinoma and Insulinoma: The Role of Aging, Genetic Factors, and Obesity.Frontiers in endocrinology · 2020Review
- Endogenous Pancreatic β Cell Regeneration: A Potential Strategy for the Recovery of β Cell Deficiency in Diabetes.Frontiers in endocrinology · 2019Review
- Mulberry Leaf Regulates Differentially Expressed Genes in Diabetic Mice Liver Based on RNA-Seq Analysis.Frontiers in physiology · 2018Article
- Nutrient regulation of pancreatic β-cell proliferation.Biochimie · 2017Review
- The tobacco-specific carcinogen-operated calcium channel promotes lung tumorigenesis via IGF2 exocytosis in lung epithelial cells.Nature communications · 2016Article
- β-cell insulin receptor deficiency during in utero development induces an islet compensatory overgrowth response.Oncotarget · 2016Article
- Milk--A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation.International journal of molecular sciences · 2015Review
- A live-cell, high-content imaging survey of 206 endogenous factors across five stress conditions reveals context-dependent survival effects in mouse primary beta cells.Diabetologia · 2015Article
- Activation of the TOR Signalling Pathway by Glutamine Regulates Insect Fecundity.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IGF2 is an autocrine ligand for the beta cell IGF1R receptor and GLP-1 increases the activity of this autocrine loop by enhancing IGF1R expression, a mechanism that mediates the trophic effects of GLP-1 on beta cell mass and function. Here, we investigated the regulation of IGF2 biosynthesis and secretion. We showed that glutamine rapidly and strongly induced IGF2 mRNA translation using reporter constructs transduced in MIN6 cells and primary islet cells. This was followed by rapid secretion of IGF2 via the regulated pathway, as revealed by the presence of mature IGF2 in insulin granule fractions and by inhibition of secretion by nimodipine and diazoxide. When maximally stimulated by glutamine, the amount of secreted IGF2 rapidly exceeded its initial intracellular pool and tolbutamide, and high K(+) increased IGF2 secretion only marginally. This indicates that the intracellular pool of IGF2 is small and that sustained secretion requires de novo synthesis. The stimulatory effect of glutamine necessitates its metabolism but not mTOR activation. Finally, exposure of insulinomas or beta cells to glutamine induced Akt phosphorylation, an effect that was dependent on IGF2 secretion, and reduced cytokine-induced apoptosis. Thus, glutamine controls the activity of the beta cell IGF2/IGF1R autocrine loop by increasing the biosynthesis and secretion of IGF2. This autocrine loop can thus integrate changes in feeding and metabolic state to adapt beta cell mass and function.
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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.