Cardiac adenylate cyclase activity in streptozotocin-treated rats after 4 months of diabetes: impairment of epinephrine and glucagon stimulation.
Adenylate cyclase (AC) activities of cardiac membranes prepared (a) from rats that had been made diabetic 4 months previously by a single i.v. injection (50 mg/kg) of streptozotocin (STZ), and (b) from diabetic rats which had been treated during the same period by a daily dose of long-acting insulin (2-4 U/animal), were compared with the AC activity of cardiac membranes prepared from age-matched control animals. Basal (Mg++-dependent) and Mn++ (7 mM)-dependent activities, as well as Gpp(NH)p (3 X 10(-7) M) stimulation and Ca++ (pCa = 3.9) inhibition of cardiac AC were not significantly different in the three groups. At the EC50 concentration epinephrine (5 X 10(-7) M) stimulation of AC was reduced in diabetic animals but no change was observed at higher concentrations (10(-4) M). Glucagon stimulation was impaired at both the EC50 concentration (10(-7) M) and at higher concentrations (10(-5) M). Insulin treatment of the diabetic animals partially prevented the impairment of hormone stimulation. These results confirm observations that alterations of cardiac AC activity in STZ-treated rats are indeed due to diabetes and not to STZ-toxicity and suggest that AC-coupled receptors are altered either by an diabetes-induced alteration of cardiac sarcolemma.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D009202:Cardiomyopathies / Q000201:enzymology* / Q000209:etiology; D002462:Cell Membrane / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology*; D004837:Epinephrine / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D005934:Glucagon; D000262:Adenylyl Cyclases; D002118:Calcium; D004837:Epinephrine