Related Experiment Video

Updated: May 2, 2026

Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy
08:47

Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy

Published on: December 7, 2017

12.6K

Insulin elicits a ROS-activated and an IP₃-dependent Ca²⁺ release, which both impinge on GLUT4 translocation

Ariel Contreras-Ferrat1, Paola Llanos, César Vásquez

  • 1Centro de estudios Moleculares de la Célula, Facultad de Medicina; Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.

Journal of Cell Science
|February 27, 2014
PubMed

Insights

Insulin signaling involves hydrogen peroxide (H2O2) production, originating from NOX2 NADPH oxidase, which enhances glucose transporter type 4 (GLUT4) translocation in muscle cells. This process also involves calcium signaling pathways parallel to the canonical insulin pathway.

Area of Science:

  • Cellular Metabolism
  • Molecular Signaling
  • Muscle Physiology

Background:

  • Insulin signaling regulates glucose uptake in skeletal muscle, a process critical for maintaining blood glucose homeostasis.
  • The role of hydrogen peroxide (H2O2) in insulin-stimulated glucose transport remains unclear, despite its generation during insulin signaling.
  • Understanding the molecular mechanisms underlying insulin action is crucial for metabolic disease research.

Purpose of the Study:

  • To investigate the origin and contribution of hydrogen peroxide (H2O2) to insulin-dependent glucose transport and GLUT4 translocation in skeletal muscle cells.
  • To elucidate the signaling pathways, including calcium dynamics, that mediate insulin's effects on glucose uptake.
  • To explore the interplay between canonical insulin signaling and alternative pathways involving reactive oxygen species and calcium.

Main Methods:

  • Utilized skeletal muscle cells to examine the effects of H2O2 and insulin on glucose transporter type 4 (GLUT4) translocation.
  • Employed antioxidants (N-acetyl L-cysteine, Trolox) and specific inhibitors (gp91-ds-tat, Xestospongin B) to probe the involvement of NADPH oxidase and IP3 receptors.
  • Investigated the role of ryanodine receptors (RyRs) and calcium (Ca2+) signaling in insulin-stimulated glucose transport using agonists and knockdown techniques.

Main Results:

  • Hydrogen peroxide (H2O2) addition mimicked and enhanced insulin's effect on GLUT4myc translocation, indicating a role for H2O2 in this process.
  • Inhibition of p47(phox)-NOX2 NADPH oxidase or its knockdown reduced insulin-dependent GLUT4myc translocation and H2O2 production.
  • Insulin stimulated RyR1-mediated Ca2+ release via S-glutathionylation, acting in parallel to IP3-receptor-mediated Ca2+ uptake, both contributing to glucose uptake.

Conclusions:

  • Insulin signaling utilizes hydrogen peroxide (H2O2) generated by NOX2 NADPH oxidase to promote GLUT4 translocation in skeletal muscle.
  • Insulin engages parallel calcium signaling pathways, involving RyR1-mediated Ca2+ release and IP3-receptor-mediated mitochondrial Ca2+ uptake, to enhance glucose uptake.
  • These findings reveal a complex interplay of ROS and calcium signaling in insulin action, offering new insights into metabolic regulation.
Keywords:
Ca2+ transientInositol 1,4,5-trisphosphateMetabolic controlNOX2RyR1Skeletal muscle

More Related Videos

Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate05:58

Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate

Published on: June 25, 2019

7.0K
Detection of Detergent-sensitive Interactions Between Membrane Proteins10:09

Detection of Detergent-sensitive Interactions Between Membrane Proteins

Published on: March 7, 2018

5.3K

Related Concept Videos

Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
6.3K
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
6.0K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
2.8K
Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
7.5K
Glucose Absorption Into the Small Intestine01:26

Glucose Absorption Into the Small Intestine

Complex carbohydrates consumed cannot be absorbed into the small intestine in their original form. First, they must be hydrolyzed to a monosaccharide form such as glucose or galactose. These monosaccharides are then transported across the intestinal membrane and into the blood via transcellular transport. The intestinal epithelial cells allow the movement of these monosaccharides with a defined 'entry' through membrane transporter proteins present on their apical membrane and...
34.0K
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...
1.3K