Reversal of defective G-proteins and adenylyl cyclase/cAMP signal transduction in diabetic rats by vanadyl sulphate therapy.
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 alpha) as well as inhibitory (Gi alpha-2 and Gi alpha-3) as determined by immunoblotting techniques were also significantly higher in the STZ-D rat liver, however, the inhibitory effects of oxotremorine and low concentrations of GTP gamma 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.
Anand-Srivastava
M B
MB
Department of Physiology, University of Montreal, Quebec, Canada.
McNeill
J H
JH
Yang
X P
XP
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage; D008099:Liver / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D017968:Vanadium Compounds / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D007328:Insulin; D017968:Vanadium Compounds; C034028:vanadyl sulfate; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases