Research

Energy balance

Activation of AMP-activated protein kinase (AMPK) increases skeletal muscle GLUT4 gene expression by phosphorylating the transcriptional repressor HDAC5 at serines 259 and 498, causing its nuclear export and relieving transcriptional repression.

Skeletal muscle adapts to energy stress (like exercise) by activating AMPK, which physically removes roadblocks (HDAC5) from the DNA, allowing the body to produce more GLUT4 transporters. This is a fundamental biological mechanism for improving insulin sensitivity and glucose handling in muscle tissue.

GoodSupportsHIGH confidence
These data reveal a signal transduction pathway linking cellular energy charge to gene transcription directed at restoring cellular and whole-body energy balance... AMPK is an HDAC5 kinase and that AMPK regulation of HDAC5 can control GLUT4 gene expression in human skeletal muscle.
Sean L. McGee et al. · Diabetes · 2008

Why this rating

High-quality in vitro and ex vivo evidence using human primary myotubes, site-directed mutagenesis, and specific kinase assays, though not a clinical trial.

Source

AMP-Activated Protein Kinase Regulates GLUT4 Transcription by Phosphorylating Histone Deacetylase 5

Sean L. McGee et al. · Diabetes · 2008

DOI 10.2337/db07-0843

mechanism_only · n=5Cited 448×
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DOI resolved against Crossref · corpus check 2026-06-10

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