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Reversal of defective G-proteins and adenylyl cyclase/cAMP signal transduction in diabetic rats by vanadyl sulphate therapy

  • Part II: Biochemical and Physiological Studies
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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 (Gsα) as well as inhibitory (Giα-2 and Giα-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 GTPγS 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.

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Abbreviations

NECA:

N-ethylcarboxamideadenosine

Iso:

Isoproterenol

Glu:

Glucagon

FSK:

forskolin

GTPγS:

guanosine 5′-[γ-thio]triphosphate

Gs:

stimulatory guanine nucleotide regulatory protein

Gi:

inhibitory guanine nucleotide regulatory protein

STZ:

streptozotocin

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Author notes

  1. Madhu B. Anand-Srivastava (recipient of the Medical Research Council Scientist Award)

    Present address: Medical Research Council of Canada, Canada

Authors and Affiliations

  1. Department of Physiology, University of Montreal, Succursale A, C.P. 6128, H3C 3J7, Montreal, Quebec, Canada

    Madhu B. Anand-Srivastava (recipient of the Medical Research Council Scientist Award) & Xiao-Ping Yang

  2. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada

    John H. McNeill

Authors
  1. Madhu B. Anand-Srivastava
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  2. John H. McNeill
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  3. Xiao-Ping Yang
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Additional information

This work was supported by grants from Medical Research Council and Canadian Diabetes Association.

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Anand-Srivastava, M.B., McNeill, J.H. & Yang, XP. Reversal of defective G-proteins and adenylyl cyclase/cAMP signal transduction in diabetic rats by vanadyl sulphate therapy. Mol Cell Biochem 153, 113–119 (1995). https://doi.org/10.1007/BF01075925

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