Duality in the Mastoparan Action on Glucose Transport in Rat Adipocytes

Abstract

Mastoparan, a tetradecapeptide purified from wasp venom, has been shown to stimulate glucose transport in rat adipocytes although the mechanism of its action has remained undefined. Here, we characterized the action of mastoparan on glucose transport in rat adipocytes. Mastoparan at a concentration of 20 microM or more caused a dose-dependent release of lactate dehydrogenase (LDH) from the cells, which closely correlated with its stimulatory effect on glucose uptake. The mastoparan-induced glucose uptake was inhibited neither by deprivation of ATP with KCN nor by addition of phloretin, a direct inhibitor of glucose transporter, suggesting that the ability of mastoparan to stimulate glucose uptake did not derive from activation of the glucose transport system (i.e. translocation or activation of GLUT4 and/or GLUT1). On the other hand, mastoparan at a lower concentration (15 microM or below), which showed an insignificant effect on LDH release, potentiated the insulin action on glucose transport and Akt phosphorylation in the presence of adenosine deaminase. The effect of mastoparan was not additive to that of phenylisopropyladenosine and was completely abolished by pretreatment of adipocytes with pertussis toxin (1 microg/ml for 2 hours). Thus, the present study disclosed duality in the action of mastoparan on glucose uptake in rat adipocytes. At a concentration of 15 microM or less, it enhances the insulin action on glucose transport by a pertussis toxin-sensitive Gi protein-dependent mechanism. At higher concentrations, however, mastoparan increases non-specific permeability of the plasma membrane, which causes LDH release as well as glucose uptake not mediated through glucose transporter.