Thromboxane signalling links immune activation to enhanced glucose uptake in skeletal muscle.

Summary

Acute exercise increased plasma TXB2 and COX-2 expression in skeletal muscle-resident monocyte/macrophages. Thromboxane receptor stimulation (I‑BOP) boosted glucose uptake up to ~2.5-fold in muscle cells, enhanced glycogen synthesis by ~430%, activated PKA/cytoskeletal pathways linked to GLUT4 trafficking, and improved glucose tolerance in mice with a 43% increase in EDL glucose uptake. Efficacy persisted in diet-induced obese mice.

Key Findings

• Acute exercise elevates plasma TXB2 and induces PTGS2 (COX-2) in skeletal muscle monocyte/macrophages.
• Thromboxane receptor agonism (I-BOP) increases glucose uptake up to ~2.5-fold and glycogen synthesis by ~430% in skeletal muscle cells.
• Transcriptomics/signaling indicate PKA activation and cytoskeletal remodeling that promote GLUT4 trafficking.
• In vivo, thromboxane receptor stimulation improves glucose tolerance and increases EDL muscle glucose uptake by ~43%, with efficacy preserved in obese mice.

Clinical Implications

Pharmacologic modulation of thromboxane receptors could augment muscle glucose disposal and glycaemic control, potentially complementing exercise or existing antidiabetic therapies. Safety will require careful evaluation given thromboxane’s vascular effects.

Limitations

• Primarily short-term, acute interventions; durability and chronic metabolic outcomes remain unknown.
• No human interventional trial of thromboxane receptor modulation; safety considerations (e.g., thrombosis risk) not addressed.

Future Directions

Early-phase trials of selective thromboxane receptor modulators with cardiometabolic safety monitoring, and biomarker-led studies to identify responders (e.g., exercise-induced TX signatures).