δ-Opioid receptors stimulate GLUT1-mediated glucose uptake through Src- and IGF-1 receptor-dependent activation of PI3-kinase signalling in CHO cells

摘要: BACKGROUND AND PURPOSE Although opioids have been reported to affect glucose homeostasis, relatively little is known on the role of δ-opioid receptors. We investigated regulation transport by human receptors expressed in Chinese hamster ovary cells. EXPERIMENTAL APPROACH The uptake [3H]-2-deoxy-D-glucose and 3-O-[methyl-[3H]]-D-glucose response receptor ligands expression GLUT1, GLUT3 GLUT4 transporters were examined. Moreover, effects intracellular signal transduction inhibitors receptor-regulated protein phosphorylation investigated. KEY RESULTS Activation rapidly stimulated uptakes, which blocked GLUT cytochalasin B phloretin. stimulation that occurred without a change plasma membrane GLUT1 – required coupling Gi/Go proteins was independent cAMP extracellular signal-regulated kinases, suppressed blockade Src insulin-like growth factor-1 (IGF-1R) tyrosine kinases. Inhibition phosphatidylinositol 3-kinase (PI3K) wortmannin or LY294002 PI3Kα, but not γ, isoform-selective greatly reduced uptake. attenuated overexpressing dominant-negative kinase-deficient Akt form chemical inhibition Akt. Stimulation increased kinase Cζ/λ (PKCζ/λ) selective PKCζ/λ inhibitor slightly opioid uptake. CONCLUSIONS IMPLICATIONS δ-Opioid probably enhancing intrinsic activity through signalling cascade involving Gi/Go, Src, IGF-1R, and, minor extent, PKCζ/λ. This effect may contribute homeostasis physio-pathological conditions.