EP4: A prostanoid receptor that modulates insulin signalling in rat skeletal muscle cells

The EP4 (prostaglandin E2) receptor plays a crucial role in myogenesis and skeletal muscle regeneration, yet its involvement in regulating insulin-dependent metabolic pathways is not well characterised. Our research investigates the expression of EP4 in rat skeletal L6 myotubes and its impact on insulin signalling. We found that activation of EP4 by selective agonists disrupts insulin signalling and insulin-stimulated glucose uptake. This impairment is associated with enhanced pro-inflammatory NF-κB signalling, a process that can be attenuated by EP4 antagonists. Importantly, EP4 antagonism also reduces NF-κB activation induced by palmitate and the associated reduction in insulin signalling, an effect not replicated by antagonists of EP1, EP2, or EP3 receptors. These observations indicate that the EP4 receptor is a modulator of insulin action and that it contributes to fatty-acid-induced insulin resistance in skeletal muscle cells. Our findings suggest that EP4 could be a potential therapeutic target for managing insulin resistance.