Related Experiment Video

Updated: May 16, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Epidermal growth factor receptor transactivation is necessary for glucagon-like peptide-1 to protect PC12 cells from

Ryosuke Kimura1, Masahiro Okouchi, Takashi Kato

  • 1Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. CQR00501 @ nifty.com

Neuroendocrinology
|November 14, 2012
PubMed
Abstract

Insights

Glucagon-like peptide-1 (GLP-1) protects against diabetic encephalopathy by activating epidermal growth factor receptor (EGFR) transactivation. This signaling pathway, involving PI3K/Akt/mTOR/GCLc/redox, reduces neural cell apoptosis in diabetic conditions.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Cell Biology

Background:

  • Diabetic encephalopathy, a complication of long-standing diabetes, causes cognitive impairment and dementia.
  • Glucagon-like peptide-1 (GLP-1) has shown potential neuroprotective properties against neural cell apoptosis.

Purpose of the Study:

  • To investigate if GLP-1 exposure triggers epidermal growth factor receptor (EGFR) transactivation.
  • To determine if GLP-1 signaling involves the PI3K/Akt/mTOR/GCLc/redox pathway in protecting against methylglyoxal (MG)-induced apoptosis.

Main Methods:

  • PC12 cells were exposed to MG and GLP-1, with or without EGFR transactivation inhibitors.
  • Phosphorylation of EGFR and Akt was monitored using Western blotting and DAPI staining.

Main Results:

  • GLP-1 treatment rescued PC12 cells from MG-induced apoptosis.
  • This protection was abrogated by inhibitors of EGFR transactivation, suggesting GLP-1 acts via EGFR.
  • GLP-1 induced EGFR and Akt phosphorylation, indicating activation of the PI3K/Akt pathway.

Conclusions:

  • GLP-1 exerts neuroprotective effects against MG-induced apoptosis in PC12 cells.
  • These effects are mediated by EGFR transactivation and subsequent signaling through the PI3K/Akt/mTOR/GCLc/redox pathway.

More Related Videos

Therapeutic Gene Delivery and Transfection in Human Pancreatic Cancer Cells using Epidermal Growth Factor Receptor-targeted Gelatin Nanoparticles08:35

Therapeutic Gene Delivery and Transfection in Human Pancreatic Cancer Cells using Epidermal Growth Factor Receptor-targeted Gelatin Nanoparticles

Published on: January 4, 2012

Mixed Primary Cultures of Murine Small Intestine Intended for the Study of Gut Hormone Secretion and Live Cell Imaging of Enteroendocrine Cells09:16

Mixed Primary Cultures of Murine Small Intestine Intended for the Study of Gut Hormone Secretion and Live Cell Imaging of Enteroendocrine Cells

Published on: April 20, 2017

Related Concept Videos

GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...