Effects of vanadium treatment on the alterations of cardiac glycogen phosphorylase and phosphorylase kinase in streptozotocin-induced chronic diabetic rats.
Supersensitivity to isoproterenol (ISO) induced activation of cardiac phosphorylase in diabetic rat heart has been previously demonstrated and was also reproduced in this study. To explore further the nature of this supersensitivity, we examined the activity of phosphorylase kinase and the level of cyclic AMP (cAMP) in this tissue. We observed a significantly enhanced activation of phosphorylase kinase but no increase in cAMP levels in response to ISO stimulation in diabetic rat heart, suggesting that the supersensitivity of phosphorylase activation in diabetic heart may result from an enhanced activation of phosphorylase kinase that does not involve the cAMP pathway. On the other hand, perfusion of diabetic rat heart with verapamil (5 x 10(-8) M) prior to ISO stimulation abolished the enhanced cardiac phosphorylase activation, suggesting a role for calcium in the supersensitivity of phosphorylase activation. Furthermore, treatment of the diabetic rats with an insulin-like compound, vanadyl sulphate, completely abolished the enhanced cardiac phosphorylase activation and restored the increase in ISO-induced cAMP elevation in diabetic heart. The present study has provided further information on the changes of phosphorylase activation in the diabetic rat heart and demonstrated beneficial effects of vanadyl sulphate on the pathway leading to phosphorylase activation in diabetic rat heart.
Liu
H
H
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
McNeill
J H
JH
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010764:Phosphorylase Kinase / Q000187:drug effects* / Q000378:metabolism; D006005:Phosphorylases / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014639:Vanadium / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D014639:Vanadium; D014700:Verapamil; D000242:Cyclic AMP; D006005:Phosphorylases; D010764:Phosphorylase Kinase