Creatine feeding increases GLUT4 expression in rat skeletal muscle

Area of Science:

• Exercise Physiology
• Molecular Biology
• Nutritional Science

Background:

• Glucose transporter type 4 (GLUT4) is crucial for insulin-stimulated glucose uptake in skeletal muscle.
• Creatine is a popular supplement known for enhancing muscle energy metabolism and performance.
• The molecular mechanisms by which creatine influences GLUT4 expression remain incompletely understood.

Purpose of the Study:

• To investigate the effect of creatine monohydrate supplementation on GLUT4 gene expression in rat skeletal muscle.
• To explore the potential role of creatine in regulating GLUT4 protein and mRNA levels.
• To examine the impact of creatine on glucose transport, glycogen content, and related signaling pathways.

Main Methods:

• Female Wistar rats were supplemented with creatine monohydrate (2%) or control chow for 3 weeks.
• GLUT4 protein and mRNA levels were quantified in various skeletal muscles (EDL, triceps, epitrochlearis).
• Insulin-stimulated glucose transport, glycogen content, AMPK phosphorylation, and transcription factor MEF2 activity were assessed.

Main Results:

• Creatine feeding significantly increased GLUT4 protein levels in EDL, triceps, and epitrochlearis muscles.
• Triceps GLUT4 mRNA levels doubled, and epitrochlearis muscle glycogen content increased by approximately 40% in creatine-fed rats.
• Creatine supplementation elevated AMP-activated protein kinase (AMPK) phosphorylation and increased the nuclear content and DNA binding activity of MEF2 transcription factors.

Conclusions:

• Creatine supplementation enhances GLUT4 gene expression in rat skeletal muscle.
• Increased MEF2 transcription factor activity appears to be a key mechanism mediating creatine's effects on GLUT4.
• These findings suggest creatine may improve glucose homeostasis in skeletal muscle through enhanced GLUT4 regulation.