ArticleDiabetes2014
Palmitate induces mRNA translation and increases ER protein load in islet β-cells via activation of the mammalian target of rapamycin pathway.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- The effects of free fatty acid-free bovine serum albumin and palmitate on pancreatic β-cell function.Islets · 2025Article
- Autophagy-lysosome pathway in insulin & glucagon homeostasis.Frontiers in endocrinology · 2025Review
- Evaluating the impact of lipids in isolated islet research.Frontiers in endocrinology · 2025Review
- Inhibition of the Eukaryotic Initiation Factor-2-α Kinase PERK Decreases Risk of Autoimmune Diabetes in Mice.bioRxiv : the preprint server for biology · 2024Article
- Regulation of autophagy by perilysosomal calcium: a new player in β-cell lipotoxicity.Experimental & molecular medicine · 2024Review
- Sustained hyperglycemia specifically targets translation of mRNAs for insulin secretion.The Journal of clinical investigation · 2023Article
- Restoring connexin-36 function in diabetogenic environments precludes mouse and human islet dysfunction.The Journal of physiology · 2023Article
- Deoxyhypusine synthase mutations alter the post-translational modification of eukaryotic initiation factor 5A resulting in impaired human and mouse neural homeostasis.HGG advances · 2023Article
- Article
- Protein translation paradox: Implications in translational regulation of aging.Frontiers in cell and developmental biology · 2023Review
- A multi-omics approach identifies pancreatic cancer cell extracellular vesicles as mediators of the unfolded protein response in normal pancreatic epithelial cells.Journal of extracellular vesicles · 2022Article
- Review
- The Pancreatic ß-cell Response to Secretory Demands and Adaption to Stress.Endocrinology · 2021Review
- Deoxyhypusine synthase, an essential enzyme for hypusine biosynthesis, is required for proper exocrine pancreas development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Molecular Mechanisms of Apoptosis Induction and Its Regulation by Fatty Acids in Pancreatic β-Cells.International journal of molecular sciences · 2021Review
- Single-Cell Transcriptional Profiling of Mouse Islets Following Short-Term Obesogenic Dietary Intervention.Metabolites · 2020Article
- Article
- Stress-Induced Translational Regulation Mediated by RNA Binding Proteins: Key Links to β-Cell Failure in Diabetes.Diabetes · 2020Review
- Hypusine biosynthesis in β cells links polyamine metabolism to facultative cellular proliferation to maintain glucose homeostasis.Science signaling · 2019Article
- Hepatic Stearoyl-CoA desaturase-1 deficiency-mediated activation of mTORC1- PGC-1α axis regulates ER stress during high-carbohydrate feeding.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Saturated free fatty acids (FFAs) have complex effects on the islet β-cell, acutely promoting adaptive hyperplasia but chronically impairing insulin release. The acute effects of FFAs remain incompletely defined. To elucidate these early molecular events, we incubated mouse β-cells and islets with palmitate and then studied mRNA translation by polyribosomal profiling and analyzed signaling pathways by immunoblot analysis. We found that palmitate acutely increases polyribosome occupancy of total RNA, consistent with an increase in mRNA translation. This effect on translation was attributable to activation of mammalian target of rapamycin (mTOR) pathways via L-type Ca(2+) channels but was independent of insulin signaling. Longer incubations led to depletion of polyribosome-associated RNA, consistent with activation of the unfolded protein response (UPR). Pharmacologic inhibition of mTOR suppressed both the acute effects of palmitate on mRNA translation and the chronic effects on the UPR. Islets from mice fed a high-fat diet for 7 days showed increases in polyribosome-associated RNA and phosphorylation of S6K, both consistent with activation of mTOR. Our results suggest that palmitate acutely activates mRNA translation and that this increase in protein load contributes to the later UPR.
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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.