AICAR administration affects glucose metabolism by upregulating the novel glucose transporter, GLUT8, in equine skeletal muscle.
Authors: de Laat M A, Robinson M A, Gruntmeir K J, Liu Y, Soma L R, Lacombe V A
Journal: Veterinary journal (London, England : 1997)
Summary
# Editorial Summary: AICAR and Glucose Transport in Equine Muscle Equine metabolic syndrome remains a significant clinical challenge, with insulin resistance limiting treatment options and affecting performance and longevity in affected horses. De Laat and colleagues investigated whether AICAR, an AMPK activator successfully used in human metabolic research, could enhance glucose uptake in equine skeletal muscle by examining changes in glucose transporters and metabolic markers following intravenous administration. The treatment triggered AMPK activation in muscle tissue and produced measurable improvements in glucose metabolism—specifically reducing blood glucose whilst simultaneously increasing insulin secretion—though notably without altering expression of the well-characterised transporters GLUT1 and GLUT4. The key discovery was a significant upregulation of GLUT8 protein expression, identifying this previously underappreciated glucose transporter as potentially important for equine muscle glucose handling and suggesting a distinct metabolic pathway from that operating in other species. These findings warrant further investigation into AICAR's therapeutic potential for managing insulin resistance in horses, particularly given the acute metabolic benefits observed; however, the practical application of this compound will depend on developing suitable formulations for clinical use and establishing efficacy in insulin-resistant animals rather than healthy horses alone.
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Practical Takeaways
- •AICAR shows promise as a potential pharmacological intervention for equine metabolic syndrome and insulin resistance, though further investigation is needed before clinical application
- •The novel glucose transporter GLUT8 appears to be a key player in equine muscle glucose uptake and may be a target for managing metabolic disease in horses
- •AMPK activation via AICAR enhances both muscle glucose uptake and pancreatic insulin secretion, suggesting multi-system metabolic benefits
Key Findings
- •AICAR administration decreased blood glucose (P<0.05) and increased insulin concentration (P<0.05) in horses
- •AICAR activated AMPK pathway, increasing phosphorylated to total AMPK ratio (P<0.05) in skeletal muscle
- •GLUT8 protein expression was significantly upregulated (P<0.05) following AICAR treatment, while GLUT1 and GLUT4 remained unchanged
- •AICAR acutely promotes muscle glucose uptake in healthy horses, suggesting therapeutic potential for managing insulin resistance