title: Identification of the molecular basis for phosphorylase hypersensitivity in cultured diabetic cardiomyocytes.
abstract: The focus of this study was to identify the molecular basis for the hypersensitive response of glycogen phosphorylase activation to epinephrine stimulation in alloxan diabetic-derived cardiomyocytes. Cyclic AMP levels were found not to be significantly different between normal and diabetic-derived cells while cGMP concentrations were found consistently to be significantly lower in diabetic-derived cells than in normal cells. Treatment with cyclic GMP analogues did not affect phosphorylase activation by epinephrine in normal cardiomyocytes whereas, IBMX, a nonselective phosphodiesterase inhibitor, had a significant effect on basal and agonist-stimulated phosphorylase activity in both normal and diabetic-derived cardiomyocytes. Differences in the time course for the rate of decay of phosphorylase a from agonist-stimulated to basal levels were observed between normal and diabetic cells. After 3 h in primary culture, phosphorylase a activity returned to basal levels more quickly in normal than in diabetic-derived cells while after 24 h in culture, the time for phosphorylase a decay was not significantly different between normal and diabetic myocytes and was longer than the 3 h response. After 3 h response. After 3 h in primary culture, no significant difference in phosphorylase kinase activity was observed between normal and diabetic-derived cells exposed to epinephrine whereas, after 24 h in culture, phosphorylase kinase activity was significantly decreased in diabetic cells under basal and agonist-stimulation conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01655, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Buczek-Thomas
authors.forename: T B
authors.initials: TB
authors.lastname: Miller
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004342:Drug Hypersensitivity / Q000201:enzymology* / Q000473:pathology; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D006005:Phosphorylases / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
chemical_list: D006005:Phosphorylases; D004837:Epinephrine