Got glycogen? An energy resource in HIF-mediated prevention of ischemic kidney injury
Related Experiment Video
Updated: Dec 25, 2025

Use of a Hanging-weight System for Liver Ischemia in Mice
Published on: August 7, 2012
1Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center and Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Abstract:
Hypoxia-inducible factor activation reprograms glucose metabolism and leads to glycogen accumulation in multiple cell types. In this issue of Kidney International, Ito and colleagues demonstrate that pharmacologic inhibition of hypoxia-inducible factor-prolyl hydroxylase domain oxygen sensors in renal epithelial cells enhances glycogen synthesis and protects from subsequent hypoxia and glucose deprivation. In vivo studies advance the concept that renal glycogen metabolism contributes to cytoprotection afforded by pre-ischemic hypoxia-inducible factor-prolyl hydroxylase domain inhibition.
Insights
Pharmacologic inhibition of hypoxia-inducible factor-prolyl hydroxylase domain sensors boosts glycogen synthesis in renal cells. This enhances cellular protection against hypoxia and glucose deprivation, suggesting a role for renal glycogen metabolism in cytoprotection.
Area of Science:
- Cellular metabolism
- Renal physiology
- Hypoxia-inducible factors
Background:
- Hypoxia-inducible factor (HIF) activation alters glucose metabolism, promoting glycogen storage.
- Renal cells are susceptible to damage from hypoxia and glucose deprivation.
Purpose of the Study:
- To investigate the role of hypoxia-inducible factor-prolyl hydroxylase domain (HIF-PHD) inhibition in renal cell metabolism and protection.
- To determine if enhancing glycogen synthesis via HIF-PHD inhibition confers cytoprotection.
Main Methods:
- Pharmacologic inhibition of HIF-PHD oxygen sensors in renal epithelial cells.
- Assessment of glycogen synthesis and cellular response to hypoxia/glucose deprivation.
- In vivo studies to evaluate cytoprotective effects in a pre-ischemic model.
Main Results:
- Inhibition of HIF-PHD in renal epithelial cells enhanced glycogen synthesis.
- Enhanced glycogen synthesis led to protection against subsequent hypoxia and glucose deprivation.
- In vivo studies supported the role of renal glycogen metabolism in cytoprotection.
Conclusions:
- Pharmacologic HIF-PHD inhibition can reprogram renal cell metabolism to favor glycogen synthesis.
- Pre-ischemic HIF-PHD inhibition offers cytoprotection through enhanced renal glycogen metabolism.
- Renal glycogen metabolism is a key contributor to cellular resilience against ischemic injury.
Related Concept Videos
Acute Kidney Injury II: Pathophysiology
Acute Kidney Injury IV: Diagnostic Studies and Prevention
Acute Kidney Injury I: Introduction
Acute Kidney Injury V: Interprofessional Care
Metabolic States of the Body: The Postabsorptive State
Initially, glycogen stored in the liver is broken down to release glucose into the bloodstream, while glycogen in the muscles is broken down to supply glucose for energy directly within the muscle cells. As glycogen stores diminish,...
Metabolic States of the Body: Fasting and Starvation

