Role of α1A-adrenoceptor in the regulation of glucose uptake into white adipocyte of rats in vitro

In an attempt to know the functional role of alpha (1A)-adrenoceptors in adipose tissue, white adipocytes (WAT) of Wister rats were used to investigate the change of glucose uptake after pharmacological activation of alpha (1)-adrenoceptors. Methoxamine enhanced the uptake of radioactive glucose into isolated WAT in a concentration-dependent manner. Translocation of glucose transporter (GLUT4) from cytosol to membrane was also stimulated with methoxamine. Action of methoxamine to raise glucose uptake was abolished in WAT pre-incubated with the antagonists, both tamsulosin and WB 4101, at concentrations sufficient to block alpha (1A)-adrenoceptors. However, chlorethylclonidine (CEC), the antagonist of alpha (1B)-adrenoceptors, showed the inhibition of methoxsunine-induced action only at a higher concentration. Even under the treatment with maximal concentration of CEC, methoxamine can produce action about 80% of the vehicle-treated control. The major role of cc,, adrenoceptors in the stimulation of glucose uptake by methoxamine can thus be considered. In the presence of specific inhibitor of phospholipase C (PLC), U73312, methoxamine-stimulated glucose uptake into WAT was reduced in a concentration-dependent manner and U73343, the negative control of U73312, did not affect the action of methoxamine. Moreover, chelerythrine and GF 109203X diminished the methoxamine-stimulated glucose uptake at a concentration sufficient to inhibit protein kinase C (PKC). Inhibition of phosphoinositide-3 kinase (PI-3 kinase) by LY294002 also abolished methoxamine-stimulated glucose uptake. Therefore, the obtained data suggest that an activation of alpha (1A)-adrenoceptors, presence in WAT, by agonist and/or neurotransmitter may increase the glucose uptake via PLC-PKC pathway and the activation of PI-3 kinase. (C) 2000 Elsevier Science B.V. All rights reserved.