INSULIN-LIKE EFFECTS OF TUNGSTATE AND MOLYBDATE - MEDIATION THROUGH INSULIN-RECEPTOR INDEPENDENT PATHWAYS

The insulin-like effects of tungstate (W) and molybdate (Mo) were stud ied in rat adipocytes and compared to those of vanadate. Other than be ing less potent, W and Mo resembled vanadate in stimulating lipogenesi s, in activating glucose oxidation, in enhancing rate of hexose uptake , and in inhibiting lipolysis. Tungstate and molybdate did not activat e the insulin-receptor tyrosine kinase (InsRTK). Quercetin which block s InsRTK activity and insulin stimulation of glucose metabolism, faile d to inhibit when these bioeffects were stimulated by W or Mo. The met alooxide, however, activated a staurosporine sensitive non receptor, c ytosolic protein tyrosine kinase (CytPTK), and staurosporine blocked W or Mo dependent lipogenesis in rat adipocytes. Staurosporine did not prevent Mo and W either from activating hexose transport, or from inhi biting lipolysis. Tungstate and molybdate were less effective than van adate in inhibiting adipose PTPases in cell free systems. Membranal PT Pases were more sensitive to W and Mo inhibition than cytosolic PTPase s. While the presence of a nucleophile such as hydroxylamine reversed inhibition of PTPase by vanadate it did not affect inhibition by W or Mo. In summary, the insulinomimetic effects of W and Mo appear to rese mble qualitatively that of vanadate in all respects. Both act in an in sulin receptor-independent-fashion, activate CytPTK and trigger additi onal effects that are not mediated by the InsRTK or by CytPTK. The qua ntitative differences may be attributed to reduced capacity of W and M o relative to vanadate to inhibit the relevant PTPases in intact cells .