ArticleCell death & disease2014
The proapoptotic BH3-only proteins Bim and Puma are downstream of endoplasmic reticulum and mitochondrial oxidative stress in pancreatic islets in response to glucotoxicity.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 108 citations in OpenAlex.
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- Purification and Characterization of Gamma-Aminobutyric Acid (GABA) from E. faecium BS5 and Its Antidiabetic Efficacy in Streptozotocin-Induced Diabetic Rats.Probiotics and antimicrobial proteins · 2026Article
- Multifaceted Roles of Bcl-2 Family Proteins: Regulatory Roles in Apoptosis, Physiological Functions, and Therapeutic Potential.Current medical science · 2025Review
- Integrating Spatial and Single-Nucleus Transcriptomic Data to Assess the Effects of Intrauterine Hyperglycemia on Fetal Pancreatic Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Type 2 Diabetes Mellitus: A Metabolic Model of Accelerated Aging - Multi-Organ Mechanisms and Intervention Approaches.Aging and disease · 2025Review
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- Hepatocyte programmed cell death: the trigger for inflammation and fibrosis in metabolic dysfunction-associated steatohepatitis.Frontiers in cell and developmental biology · 2024Review
- The Unfolded Protein Response: A Double-Edged Sword for Brain Health.Antioxidants (Basel, Switzerland) · 2023Review
- Mechanisms of NAT10 as ac4C writer in diseases.Molecular therapy. Nucleic acids · 2023Review
- Selenite as a dual apoptotic and ferroptotic agent synergizes with EGFR and KRAS inhibitors with epigenetic interference.Clinical epigenetics · 2023Article
- Nova1 or Bim Deficiency in Pancreatic β-Cells Does Not Alter Multiple Low-Dose Streptozotocin-Induced Diabetes and Diet-Induced Obesity in Mice.Nutrients · 2022Article
- Maladaptive positive feedback production of ChREBPβ underlies glucotoxic β-cell failure.Nature communications · 2022Article
- Targeting mitochondrial respiration and the BCL2 family in high-grade MYC-associated B-cell lymphoma.Molecular oncology · 2022Article
- ER stress-induced cell death proceeds independently of the TRAIL-R2 signaling axis in pancreatic β cells.Cell death discovery · 2022Article
- Influence of circulating nesfatin-1, GSH and SOD on insulin secretion in the development of T2DM.Frontiers in public health · 2022Article
- MLN2238 exerts its anti-tumor effectsFrontiers in pharmacology · 2022Article
- Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptosis of pancreatic beta cells is a feature of type 2 diabetes and its prevention may have therapeutic benefit. High glucose concentrations induce apoptosis of islet cells, and this requires the proapoptotic Bcl-2 homology domain 3 (BH3)-only proteins Bim and Puma. We studied the stress pathways induced by glucotoxicity in beta cells that result in apoptosis. High concentrations of glucose or ribose increased expression of the transcription factor CHOP (C/EBP homologous protein) but not endoplasmic reticulum (ER) chaperones, indicating activation of proapoptotic ER stress signaling. Inhibition of ER stress prevented ribose-induced upregulation of Chop and Puma mRNA, and partially protected islets from glucotoxicity. Loss of Bim or Puma partially protected islets from the canonical ER stressor thapsigargin. The antioxidant N-acetyl-cysteine also partially protected islets from glucotoxicity. Islets deficient in both Bim and Puma, but not Bim or Puma alone, were significantly protected from killing induced by the mitochondrial reactive oxygen species donor rotenone. Our data demonstrate that high concentrations of glucose induce ER and oxidative stress, which causes cell death mediated by Bim and Puma. We observed significantly higher Bim and Puma mRNA in islets of human donors with type 2 diabetes. This indicates that inhibition of Bim and Puma, or their inducers, may prevent beta-cell destruction in type 2 diabetes.
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