Related Experiment Video

Updated: Aug 12, 2026

Combined Intravital Microscopy and Contrast-enhanced Ultrasonography of the Mouse Hindlimb to Study Insulin-induced Vasodilation and Muscle Perfusion
08:22

Combined Intravital Microscopy and Contrast-enhanced Ultrasonography of the Mouse Hindlimb to Study Insulin-induced Vasodilation and Muscle Perfusion

Published on: March 20, 2017

Insulin and ischemia stimulate glycolysis by acting on the same targets through different and opposing signaling

Louis Hue1, Christophe Beauloye, Anne-Sophie Marsin

  • 1Hormone and Metabolic Research Unit, Christian de Duve International Institute of Cellular and Molecular Pathology, and University of Louvain Medical School, Avenue Hippocrate, 75, B-1200, Brussels, Belgium. hue@horm.ucl.ac.be

Journal of Molecular and Cellular Cardiology
|October 24, 2002
PubMed

Insights

Insulin and ischemia activate heart glycolysis via 6-phosphofructo-2-kinase (PFK-2). This study identifies a novel insulin-sensitive kinase for PFK-2 and confirms AMP-activated protein kinase (AMPK) mediates ischemic activation, revealing signaling pathway interactions.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cardiology

Background:

  • Insulin and ischemia stimulate heart glycolysis through glucose transporter (GLUT4) recruitment and 6-phosphofructo-2-kinase (PFK-2) activation.
  • PFK-2 activation increases fructose 2,6-bisphosphate, a key glycolytic stimulator.
  • Protein kinase B (PKB) and AMP-activated protein kinase (AMPK) are implicated in PFK-2 regulation.

Purpose of the Study:

  • To elucidate the mechanisms of PFK-2 activation by insulin and ischemia in the heart.
  • To identify the specific protein kinases involved in insulin- and ischemia-mediated PFK-2 activation.
  • To investigate the interplay between insulin and ischemia signaling pathways in cardiac cells.

Main Methods:

  • Partial purification of an insulin-sensitive PFK-2 kinase.
  • Enzyme activity assays to assess PFK-2 activation.
  • Investigation of protein kinase involvement (PKB, AMPK) in PFK-2 phosphorylation.
  • Analysis of signaling pathway interactions under insulin and ischemic conditions.

Main Results:

  • PKB is not required for insulin-induced PFK-2 activation.
  • A novel insulin-sensitive PFK-2 kinase, distinct from PKB, was partially purified.
  • AMPK was confirmed to mediate PFK-2 activation during ischemia.
  • Ischemia-induced intracellular acidosis inhibited insulin signaling.
  • Insulin pretreatment antagonized AMPK activation by ischemia.

Conclusions:

  • Cardiac PFK-2 activation by insulin involves a novel kinase, not PKB.
  • AMPK is the primary mediator of ischemic PFK-2 activation in the heart.
  • Insulin and ischemia signaling pathways exhibit antagonistic interactions within the heart.

More Related Videos

Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes08:03

Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes

Published on: June 25, 2017

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain08:32

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain

Published on: January 4, 2018

Related Concept Videos

What is Glycolysis?00:56

What is Glycolysis?

Overview
Cells make energy by breaking down macromolecules. Cellular respiration is the biochemical process that converts "food energy" (from the chemical bonds of macromolecules) into chemical energy in the form of adenosine triphosphate (ATP). The first step of this tightly regulated and intricate process is glycolysis. The word glycolysis originates from the Latin glyco (sugar) and lysis (breakdown). Glycolysis serves two main intracellular functions: generating ATP and generating...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
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,...
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...
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 co-secreted in...
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 this inhibition is released...