Activation of α_1A-Adrenoceptor by Andrographolide to Increase Glucose Uptake in Cultured Myoblast C₂C₁₂ Cells

Abstract

We investigated the mechanism of the plasma glucose lowering action of andrographolide, using radioactive glucose uptake into cultured myoblast C₂C₁₂ cells as the indicator. In C₂C₁₂ cells, andrographolide increased the radioactive glucose uptake in a concentration-dependent manner that was abolished by pretreatment with prazosin. Activation of α1-adrenoceptors by andrographolide was further indicated by the displacement of the [³ H]prazosin binding in C₂C₁₂ cells. The α_1A-adrenoceptor appears to have caused the displacement, because RS17053 abolished this andrographolide-stimulated glucose uptake at concentrations sufficient to block the α_1A-adrenoceptor. Inhibition of phospholipase C (PLC) with U73312 concentration-dependently decreased under the action of andrographolide in C₂C₁₂ cells. This inhibition of glucose uptake by U73122 was specific because the inactive congener, U73343, failed to influence the action of andrographolide. Moreover, both chelerythrine and GF 109203X diminished the action of andrographolide at concentrations sufficient to inhibit protein kinase C (PKC). Our data suggest that an activation of α_1A-AR by andrographolide in C₂C₁₂ cells may increase the glucose uptake via the PLC-PKC pathway.

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