Orexinergic pathway as a potential therapeutic candidate for the modulation of glucose homeostasis

The orexinergic pathway serves as a metabolic integrator, linking central glucose sensing with peripheral utilization. Its context-dependent duality, promoting glucose release in hypoglycemia and insulin sensitivity in hyperglycemia, highlights a unique regulatory role. Orexin receptors are promising therapeutic targets for diabetes and metabolic syndrome. Sex-stratified human studies are needed, as preclinical data reveal marked sexual dimorphism in orexin-mediated glucose regulation, with males exhibiting greater metabolic vulnerability to orexin deficiency.