ArticlePloS one2013
Folate deficiency triggers an oxidative-nitrosative stress-mediated apoptotic cell death and impedes insulin biosynthesis in RINm5F pancreatic islet β-cells: relevant to the pathogenesis of diabetes.
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 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Pooled it
- Impact of Adjunctive Myo-Inositol and Magnesium Therapy on Paediatric Overactive Bladder: A Retrospective Analysis.Children (Basel, Switzerland) · 2026Article
- Folic Acid Therapy is Associated with a Lower Risk of Incident Diabetes and Better Glycemic Status in Patients with Coronary Heart Disease: Findings from a Multicenter Propensity Score-Matched Analysis.Drug design, development and therapy · 2026Article
- Association between Early Pregnancy Maternal Folate and Glycemic Indices at Oral Glucose Tolerance Test: A Systematic Review and Meta-analysis.Current developments in nutrition · 2025Article
- Multiomics Characterization of a Less Invasive Microfluidic-Based Cell Sorting Technique.Journal of proteome research · 2024Article
- A causal relationship between antioxidants, minerals and vitamins and metabolic syndrome traits: a Mendelian randomization study.Diabetology & metabolic syndrome · 2023Article
- Physiological Associations between Vitamin B Deficiency and Diabetic Kidney Disease.Biomedicines · 2023Review
- Dose-response association between dietary folate and niacin intakes with diabetes among Chinese adults: a cross-sectional study.Journal of health, population, and nutrition · 2023Article
- Replacing ZnSOAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2023Article
- Folate ameliorates homocysteine-induced osteoblast dysfunction by reducing endoplasmic reticulum stress-activated PERK/ATF-4/CHOP pathway in MC3T3-E1 cells.Journal of bone and mineral metabolism · 2022Article
- Deficiency of folate and vitamin BIndian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2022Article
- Disruption of Cytosolic Folate Integrity Aggravates Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Modulates Metastatic Properties in Non-Small-Cell Lung Cancer Cells.International journal of molecular sciences · 2021Article
- Integration of single-cell datasets reveals novel transcriptomic signatures of β-cells in human type 2 diabetes.NAR genomics and bioinformatics · 2020Article
- Intakes of Folate, Vitamin BDiabetes care · 2020Article
- Restoration of skeletal muscle homeostasis by hydrogen sulfide during hyperhomocysteinemia-mediated oxidative/ER stress conditionCanadian journal of physiology and pharmacology · 2019Review
- Methyl-donor depletion of head and neck cancer cells in vitro establishes a less aggressive tumour cell phenotype.European journal of nutrition · 2018Article
- The Protective Effects of Enalapril Maleate and Folic Acid Tablets against Contrast-Induced Nephropathy in Diabetic Rats.BioMed research international · 2018Article
- Chronic folate deficiency induces glucose and lipid metabolism disorders and subsequent cognitive dysfunction in mice.PloS one · 2018Article
- Cisplatin-induced regulation of signal transduction pathways and transcription factors in p53-mutated subclone variants of hepatoma cells: Potential application for therapeutic targeting.Oncology letters · 2016Article
- Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been postulated that folic acid (folate) deficiency (FD) may be a risk factor for the pathogenesis of a variety of oxidative stress-triggered chronic degenerative diseases including diabetes, however, the direct evidence to lend support to this hypothesis is scanty. For this reason, we set out to study if FD can trigger the apoptotic events in an insulin-producing pancreatic RINm5F islet β cells. When these cells were cultivated under FD condition, a time-dependent growth impediment was observed and the demise of these cells was demonstrated to be apoptotic in nature proceeding through a mitochondria-dependent pathway. In addition to evoke oxidative stress, FD condition could also trigger nitrosative stress through a NF-κB-dependent iNOS-mediated overproduction of nitric oxide (NO). The latter compound could then trigger depletion of endoplasmic reticulum (ER) calcium (Ca(2+)) store leading to cytosolic Ca(2+) overload and caused ER stress as evidence by the activation of CHOP expression. Furthermore, FD-induced apoptosis of RINm5F cells was found to be correlated with a time-dependent depletion of intracellular glutathione (GSH) and a severe down-regulation of Bcl-2 expression. Along the same vein, we also demonstrated that FD could severely impede RINm5F cells to synthesize insulin and their abilities to secret insulin in response to glucose stimulation were appreciably hampered. Even more importantly, we found that folate replenishment could not restore the ability of RINm5F cells to resynthesize insulin. Taken together, our data provide strong evidence to support the hypothesis that FD is a legitimate risk factor for the pathogenesis of diabetes.
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Registered trials
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