A STABLE PEROXOVANADIUM COMPOUND WITH INSULIN-LIKE ACTION IN HUMAN FAT-CELLS

Aqueous solutions of peroxovanadium (pV) compounds are potent insulin- mimics in various types of cell. Since chemical instability is a probl em with these agents, we studied the insulin-like action in human fat cells of a stable pV complex, bpV(pic). It enhanced C-14-U-glucose upt ake in a dose-dependent manner by approximately twofold which was slig htly less than the effect of insulin (approximately threefold). The pV complex did not alter cell-surface insulin binding and submaximal con centrations did not influence cellular sensitivity to insulin action o n glucose uptake. The bpV(pic) inhibited the lipolytic effect of isopr enaline to the same extent as insulin; however, when the cGMP-inhibita ble low-K-m phosphodiesterase (cGI-PDE) was blocked with the specific inhibitor OPC 3911, the antilipolytic effect of insulin, but not that of bpV(pic), was completely prevented. Moreover, when lipolysis was st imulated by the non-hydrolysable cAMP analogue N-6-monobutyryl cAMP, b pV(pic), in contrast to insulin, maintained an antilipolytic effect. T hese findings indicate that bpV(pic) exerts its antilipolytic effect n ot only through cGI-PDE activation, similar to the effect of insulin, but also by means of other mechanisms. The tyrosine kinase activity of insulin receptors from human placenta was not altered by the pV compo und itself, whereas bpV(pic) clearly enhanced insulin-stimulated activ ity. In contrast, in situ tyrosine phosphorylation of the insulin rece ptor beta-subunit as well as that of several other proteins was clearl y increased in cells which were treated with bpV(pic), whereas vanadat e only amplified insulin-stimulated tyrosine phosphorylation. In concl usion, bpV(pic) exerts powerful insulin-like effects in human fat cell s and may be a new and potentially useful agent in the management of i nsulin-resistant states.