ArticleDiabetologia2012
cJUN N-terminal kinase (JNK) activation mediates islet amyloid-induced beta cell apoptosis in cultured human islet amyloid polypeptide transgenic mouse islets.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 73 citations in OpenAlex.
- Vascular Destabilization and Pericyte Detachment are Mediated by hIAPP Aggregation in Transgenic Mice.bioRxiv : the preprint server for biology · 2026Article
- PLAGL1 overexpression exacerbates type 1 diabetes by inducing β-cell apoptosis via oxidative stress-dependent dual DNA damage and cGAS/STING pathway activation.Journal of diabetes investigation · 2026Article
- Positive feedback loop between MAPK and aquaporin 7 regulates autophagy and apoptosis induced by palmitate in RIN-m5f cells.FEBS open bio · 2025Article
- Understanding the structural dynamics of human islet amyloid polypeptide: Advancements in and applications of ion-mobility mass spectrometry.Biophysical chemistry · 2024Review
- Tat-CIAPIN1 Prevents Pancreatic β-Cell Death in hIAPP-Induced RINm5F Cells and T2DM Animal Model.International journal of molecular sciences · 2023Article
- Endoplasmic Reticulum (ER) Stress and Its Role in Pancreatic β-Cell Dysfunction and Senescence in Type 2 Diabetes.International journal of molecular sciences · 2022Review
- The Use of Bioactive Compounds in Hyperglycemia- and Amyloid Fibrils-Induced Toxicity in Type 2 Diabetes and Alzheimer's Disease.Pharmaceutics · 2022Review
- CD36 Signal Transduction in Metabolic Diseases: Novel Insights and Therapeutic Targeting.Cells · 2021Review
- Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies.International journal of molecular sciences · 2021Review
- β cell aging and age-related diabetes.Aging · 2021Review
- Protein Kinases Signaling in Pancreatic Beta-cells Death and Type 2 Diabetes.Advances in experimental medicine and biology · 2021Article
- Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review.Frontiers in pharmacology · 2021Review
- Impact of Conventional and Atypical MAPKs on the Development of Metabolic Diseases.Biomolecules · 2020Review
- Alpha1-antitrypsin ameliorates islet amyloid-induced glucose intolerance and β-cell dysfunction.Molecular metabolism · 2020Article
- Oligomannuronate prevents mitochondrial dysfunction induced by IAPP in RINm5F islet cells by inhibition of JNK activation and cell apoptosis.Chinese medicine · 2020Article
- RNA-seq-based identification of Star upregulation by islet amyloid formation.Protein engineering, design & selection : PEDS · 2019Article
- Targeting the IL-1β/IL-1Ra pathways for the aggregation of human islet amyloid polypeptide in an ex vivo organ culture system of the intervertebral disc.Experimental & molecular medicine · 2019Article
- Exendin-4 prevented pancreatic beta cells from apoptosis in (Type I) diabetic mouse via keap1-Nrf2 signaling.Experimental biology and medicine (Maywood, N.J.) · 2019Article
- Apoptosis signal regulating kinase-1 and NADPH oxidase mediate human amylin evoked redox stress and apoptosis in pancreatic beta-cells.Biochimica et biophysica acta. Biomembranes · 2018Article
- The receptor for advanced glycation endproducts is a mediator of toxicity by IAPP and other proteotoxic aggregates: Establishing and exploiting common ground for novel amyloidosis therapies.Protein science : a publication of the Protein Society · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
aims/hypothesisAggregation of human islet amyloid polypeptide (hIAPP) as islet amyloid is associated with increased beta cell apoptosis and reduced beta cell mass in type 2 diabetes. Islet amyloid formation induces oxidative stress, which contributes to beta cell apoptosis. The cJUN N-terminal kinase (JNK) pathway is a critical mediator of beta cell apoptosis in response to stress stimuli including oxidative stress and exogenous application of hIAPP. We determined whether amyloid formation by endogenous hIAPP mediates beta cell apoptosis through JNK activation and downstream signalling pathways.
methodshIAPP transgenic and non-transgenic mouse islets were cultured for up to 144 h in 16.7 mmol/l glucose to induce islet amyloid in the presence or absence of the amyloid inhibitor Congo Red or a cell-permeable JNK inhibitor. Amyloid, beta cell apoptosis, JNK signalling and activation of downstream targets in the intrinsic and extrinsic apoptotic pathways were measured.
resultsJNK activation occurred with islet amyloid formation in hIAPP transgenic islets after 48 and 144 h in culture. Neither high glucose nor the hIAPP transgene alone was sufficient to activate JNK independent of islet amyloid. Inhibition of islet amyloid formation with Congo Red reduced beta cell apoptosis and partially decreased JNK activation. JNK inhibitor treatment reduced beta cell apoptosis without affecting islet amyloid. Islet amyloid increased mRNA levels of markers of the extrinsic (Fas, Fadd) and intrinsic (Bim [also known as Bcl2l11]) apoptotic pathways, caspase 3 and the anti-apoptotic molecule Bclxl (also known as Bcl2l1) in a JNK-dependent manner. CONCLUSIONS/
interpretationIslet amyloid formation induces JNK activation, which upregulates predominantly pro-apoptotic signals in both extrinsic and intrinsic pathways, resulting in beta cell apoptosis.
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