Related Experiment Video

Updated: Apr 27, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

1.1K

JNK3 is required for the cytoprotective effect of exendin 4

Hélène Ezanno1, Valérie Pawlowski2, Saida Abdelli3

  • 1Lille 2 University, University of Lille Nord de France, European Genomic Institute for Diabetes, EGID FR 3508, UMR 8199, Lille, France.

Journal of Diabetes Research
|July 16, 2014
PubMed

Insights

Glucagon-like peptide-1 (GLP1) mimetics protect beta cells from death. This study shows that the protein JNK3 is essential for GLP1 mimetic exendin-4 to prevent beta cell apoptosis, highlighting JNK3

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Biology

Background:

  • Glucagon-like peptide-1 (GLP1) mimetics offer therapeutic benefits by preserving beta cell mass in diabetes.
  • Proinflammatory cytokines contribute to beta cell dysfunction and apoptosis in diabetogenic conditions.
  • Mitogen-activated protein kinase 10 (JNK3) is known to protect insulin-secreting cells from cytokine-induced death.

Purpose of the Study:

  • To investigate the association between JNK3 expression and the protective effects of the GLP1 mimetic exendin-4.
  • To determine if JNK3 mediates the antiapoptotic actions of exendin-4 in beta cells.

Main Methods:

  • Isolated human islets and INS-1E cells were cultured with exendin-4.
  • JNK3 abundance was measured in response to exendin-4 treatment.
  • JNK3 was silenced to assess its role in exendin-4's cytoprotective effects against apoptosis induced by culture conditions and cytokines.

Main Results:

  • Exendin-4 treatment increased the abundance of JNK3 in both human islets and INS-1E cells.
  • Increased JNK3 expression correlated with enhanced survival of INS-1E cells.
  • Silencing JNK3 abolished the protective effect of exendin-4 against cytokine-induced and culture-induced apoptosis.

Conclusions:

  • JNK3 expression is upregulated by the GLP1 mimetic exendin-4.
  • JNK3 is a critical mediator of exendin-4's antiapoptotic effects in beta cells.
  • Targeting JNK3 may represent a therapeutic strategy for preserving beta cell function in diabetes.

More Related Videos

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease08:15

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease

Published on: May 10, 2024

1.1K
Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment07:55

Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment

Published on: September 25, 2017

7.4K

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
10.1K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.4K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.1K
NF-kB-dependent Signaling Pathway02:26

NF-kB-dependent Signaling Pathway

2.0K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.3K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.0K