Reversal of defective G-proteins and adenylyl cyclase/cAMP signal transduction in diabetic rats by vanadyl sulphate therapy |
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Authors: | Madhu B. Anand-Srivastava John H. McNeill Xiao-Ping Yang |
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Affiliation: | (1) Department of Physiology, University of Montreal, Succursale A, C.P. 6128, H3C 3J7 Montreal, Quebec, Canada;(2) Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada;(3) Present address: Medical Research Council of Canada, Canada |
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Abstract: | Vanadium salts exhibit a wide variety of insulinomimetic effects. In the present studies, we have examined the modulation of G-protein levels and adenylyl cyclase activity in the liver of streptozotocin-induced chronic diabetic rats (STZD) by vanadyl sulfate treatment and compared it with that of insulin. The basal enzyme activity, as well as the stimulatory effects of guanine nucleotides, glucagon, N-Ethylcarboxamideadenosine (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 (Gs ) as well as inhibitory (Gi -2 and Gi -3) as determined by immunoblotting techniques were also significantly higher in the STZ-D rat liver, however, the inhibitory effects of oxotremorine and low concentration of GTP S on adenylyl cyclase were not different in the two groups. Vanadyl sulfate and insulin treatments restored the augmented basal enzyme activity, the stimulations exerted by stimulatory inputs on adenylyl cyclase and the G-protein levels to various degrees, however, vanadyl sulfate was more effective than insulin. In addition, unlike vanadyl sulfate, insulin was unable to improve the stimulation exerted by glucagon and isoproterenol on adenylyl cyclase activity in STZD rats. These results suggest that vanadyl sulfate mimics the effects of insulin to restore the defective levels of G-proteins and adenylyl cyclase activity. From these results it may be suggested that one of the mechanisms by which vanadyl sulfate improves the glucose homeostasis in STZ-D rats may be through its ability to modulate the levels of G-proteins and adenylyl cyclase signal transduction system.Abbreviations NECA N-ethylcarboxamideadenosine - Iso Isoproterenol - Glu Glucagon - FSK forskolin - GTP S guanosine 5 -[ -thio]triphosphate - Gs stimulatory guanine nucleotide regulatory protein - Gi inhibitory guanine nucleotide regulatory protein - STZ streptozotocinThis work was supported by grants from Medical Research Council and Canadian Diabetes Association. |
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Keywords: | Adenylyl cyclase G-proteins diabetes insulin vanadate |
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