REVERSAL OF DEFECTIVE G-PROTEINS AND ADENYLYL CYCLASE CAMP SIGNAL-TRANSDUCTION IN DIABETIC RATS BY VANADYL SULFATE THERAPY/

Vanadium salts exhibit a wide variety of insulinomimetic effects. In t he present studies, we have examined the modulation of G-protein level s and adenylyl cyclase activity in the liver of streptozotocin-induced chronic diabetic rats (STZD) by vanadyl sulfate treatment and compare d it with that of insulin. The basal enzyme activity, as well as the s timulatory effects of guanine nucleotides, glucagon, N-Ethylcarboxamid eadenosine (NECA), isoproterenol, forskolin and sodium fluoride (NaF) on adenylyl cyclase were significantly increased in STZ-D rat liver as compared to control. In addition, the levels of stimulatory (Gsa) as well as inhibitory (Gi(alpha-2) and Gi(alpha-3)) as determined by immu noblotting techniques were also significantly higher in the STZ-D rat liver, however, the inhibitory effects of oxotremorine and low concent rations of GTP gamma S on adenylyl cyclase were not different in the t wo groups. Vanadyl sulfate and insulin treatments restored the augment ed basal enzyme activity, the stimulations exerted by stimulatory inpu ts on adenylyl cyclase and the G-protein levels to various degrees, ho wever, vanadyl sulfate was more effective than insulin. In addition, u nlike vanadyl sulfate, insulin was unable to improve the stimulation e xerted by glucagon and isoproterenol on adenylyl cyclase activity in S TZD rats. These results suggest that vanadyl sulfate mimics the effect s of insulin to restore the defective levels of G-proteins and adenyly l cyclase activity. From these results it may be suggested that one of the mechanisms by which vanadyl sulfate improves the glucose homeosta sis in STZ-D rats may be through its ability to modulate the levels of G-proteins and adenylyl cyclase signal transduction system.