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

TY - JOUR

T1 - EP4

T2 - A prostanoid receptor that modulates insulin signalling in rat skeletal muscle cells

AU - Nisr, Raid B.

AU - Shah, Dinesh S.

AU - Hundal, Harinder S.

N1 - Publisher Copyright: © 2024 The Authors

PY - 2025/2

Y1 - 2025/2

N2 - 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.

AB - 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.

KW - Cyclooxygenase-2

KW - Prostaglandin E2

KW - NFkB

KW - Glucose transport

UR - https://www.scopus.com/pages/publications/85210066541

U2 - 10.1016/j.cellsig.2024.111516

DO - 10.1016/j.cellsig.2024.111516

M3 - Article

C2 - 39592018

SN - 0898-6568

VL - 126

JO - Cellular Signalling

JF - Cellular Signalling

M1 - 111516

ER -