ArticlePloS one2013
Free fatty acid induces endoplasmic reticulum stress and apoptosis of β-cells by Ca2+/calpain-2 pathways.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 97 citations in OpenAlex.
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- Triglycerides, Glucose Metabolism, and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Induction of hyperlipidemic pancreatitis by different fatty acids: A narrative review.World journal of gastroenterology · 2025Review
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- Role of STIM1 in the Regulation of Cardiac Energy Substrate Preference.International journal of molecular sciences · 2023Review
- Tianhuang formula regulates adipocyte mitochondrial function by AMPK/MICU1 pathway in HFD/STZ-induced T2DM mice.BMC complementary medicine and therapies · 2023Article
- Too much of a good thing: The case of SOCE in cellular apoptosis.Cell calcium · 2023Review
- Effect of Isoquercitrin on Free Fatty Acid-Induced Lipid Accumulation in HepG2 Cells.Molecules (Basel, Switzerland) · 2023Article
- NADPH Oxidases Connecting Fatty Liver Disease, Insulin Resistance and Type 2 Diabetes: Current Knowledge and Therapeutic Outlook.Antioxidants (Basel, Switzerland) · 2022Review
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- Differential Physiological, Transcriptomic, and Metabolomic Responses ofFrontiers in plant science · 2022Article
- Intracellular Ca2+ signaling and ORAI calcium release-activated calcium modulator 1 are associated with hepatic lipidosis in dairy cattle.Journal of animal science · 2021Article
- Molecular Mechanisms of Apoptosis Induction and Its Regulation by Fatty Acids in Pancreatic β-Cells.International journal of molecular sciences · 2021Review
- Low-density lipoprotein cholesterol : high-density lipoprotein cholesterol ratio is associated with incident diabetes in Chinese adults: A retrospective cohort study.Journal of diabetes investigation · 2021Article
- Mitochondrial dysfunction in nonalcoholic fatty liver disease and alcohol related liver disease.Translational gastroenterology and hepatology · 2021Review
- Calpain-2 activity promotes aberrant endoplasmic reticulum stress-related apoptosis in hepatocytes.World journal of gastroenterology · 2020Article
- Mechanisms by which PE21, an extract from the white willowOncotarget · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysfunction of β-cells is a major characteristic in the pathogenesis of type 2 diabetes mellitus (T2DM). The combination of obesity and T2DM is associated with elevated plasma free fatty acids (FFAs). However, molecular mechanisms linking FFAs to β-cell dysfunction remain poorly understood. In the present study, we identified that the major endoplasmic reticulum stress (ERS) marker, Grp78 and ERS-induced apoptotic factor, CHOP, were time-dependently increased by exposure of β-TC3 cells to FFA. The expression of ATF6 and the phosphorylation levels of PERK and IRE1, which trigger ERS signaling, markedly increased after FFA treatments. FFA treatments increased cell apoptosis by inducing ERS in β-TC3 cells. We also found that FFA-induced ERS was mediated by the store-operated Ca(2+) entry through promoting the association of STIM1 and Orai1. Moreover, calpain-2 was required for FFA-induced expression of CHOP and activation of caspase-12 and caspase-3, thus promoting cell apoptosis in β-TC3 cells. Together, these results reveal pivotal roles for Ca(2+)/calpain-2 pathways in modulating FFA-induced β-TC3 cell ERS and apoptosis.
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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.