Related Experiment Video
Updated: Jul 2, 2026

Isolated Pancreatic Islet Treatment and Apoptosis Measurement
Published on: May 2, 2025
JunB Inhibits ER Stress and Apoptosis in Pancreatic Beta Cells
Esteban N Gurzov1, Fernanda Ortis, Latifa Bakiri
1Laboratory of Experimental Medicine, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Abstract:
Cytokines contribute to pancreatic beta-cell apoptosis in type 1 diabetes (T1D) by modulation of beta-cell gene expression networks. The transcription factor Activator Protein-1 (AP-1) is a key regulator of inflammation and apoptosis. We presently evaluated the function of the AP-1 subunit JunB in cytokine-mediated beta-cell dysfunction and death. The cytokines IL-1beta+IFN-gamma induced an early and transitory upregulation of JunB by NF-kappaB activation. Knockdown of JunB by RNA interference increased cytokine-mediated expression of inducible nitric oxide synthase (iNOS) and endoplasmic reticulum (ER) stress markers, leading to increased apoptosis in an insulin-producing cell line (INS-1E) and in purified rat primary beta-cells. JunB knockdown beta-cells and junB(-/-) fibroblasts were also more sensitive to the chemical ER stressor cyclopiazonic acid (CPA). Conversely, adenoviral-mediated overexpression of JunB diminished iNOS and ER markers expression and protected beta-cells from cytokine-induced cell death. These findings demonstrate a novel and unexpected role for JunB as a regulator of defense mechanisms against cytokine- and ER stress-mediated apoptosis.
Insights
The transcription factor JunB protects pancreatic beta-cells from apoptosis in type 1 diabetes. Reducing JunB levels increases cell death from cytokine and ER stress, while increasing JunB offers protection.
Area of Science:
- Immunology
- Endocrinology
- Molecular Biology
Background:
- Cytokines promote pancreatic beta-cell apoptosis in type 1 diabetes (T1D) by altering gene expression.
- The transcription factor Activator Protein-1 (AP-1) is crucial in regulating inflammation and apoptosis.
Purpose of the Study:
- To investigate the role of the AP-1 subunit JunB in cytokine-induced beta-cell dysfunction and death.
- To understand JunB's protective mechanisms against endoplasmic reticulum (ER) stress.
Main Methods:
- Utilized RNA interference (RNAi) to knock down JunB expression in INS-1E cells and primary rat beta-cells.
- Employed adenoviral vectors for JunB overexpression.
- Assessed apoptosis, inducible nitric oxide synthase (iNOS) expression, and ER stress markers.
- Tested sensitivity to the chemical ER stressor cyclopiazonic acid (CPA).
Main Results:
- Cytokines (IL-1beta+IFN-gamma) transiently upregulated JunB via NF-kappaB activation.
- JunB knockdown exacerbated cytokine-induced iNOS expression, ER stress, and apoptosis.
- JunB-deficient cells showed increased sensitivity to ER stress.
- JunB overexpression protected beta-cells from cytokine-induced apoptosis and reduced stress markers.
Conclusions:
- JunB acts as a novel, unexpected regulator of defense against cytokine- and ER stress-induced apoptosis in beta-cells.
- JunB plays a protective role in maintaining beta-cell function and survival under inflammatory conditions relevant to T1D.
Related Concept Videos
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
Insulin and C-peptide are co-secreted in...
Insulin Secretory Vesicles
Role of ER in the Secretory Pathway
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Cells and Secretions of the Pancreas
Exocrine function is carried out by acinar cells, organized into clusters known as acini. These cells contribute to digestion by releasing substantial quantities of enzyme-rich, alkaline digestive juices.
Concurrently, the dispersed clusters of endocrine cells throughout the...
Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...
Cell Specific Gene Expression
