Altered regulation of cardiac glycogen metabolism in spontaneously diabetic rats.
Isolated perfused hearts from control Bio-Breeding/Worcester (BB/W) rats and spontaneously diabetic BB/W rats were studied to determine whether metabolic abnormalities that are expressed in alloxan-diabetic rats in the regulation of enzymes involved in glycogen metabolism could be observed in this non-chemically induced insulin-deficient rat. Perfusion of hearts from control rats with 10(-8) M insulin for 10 min resulted in activation of glycogen synthase (30% synthase I without insulin to 44% synthase I with insulin). Perfusion of hearts from BB/W diabetic rats demonstrated a lack of acute synthase activation with insulin and a 45% decrease in synthase phosphatase activity. Perfusion of hearts from BB/W diabetic rats with 0.28 microM epinephrine for 1 min resulted in a greater activation of phosphorylase (44% phosphorylase a) than that observed in BB/W control hearts (31% phosphorylase a) perfused under the same conditions. Epinephrine produced similar changes in cyclic AMP accumulation, protein kinase activation, and phosphorylase kinase activation in perfused hearts of BB/W control and diabetic rats. Further, phosphorylase phosphatase activities were not changed by epinephrine or insulin deficiency. These studies further document metabolic abnormalities in the BB/W diabetic rat that are attributable to insulin deficiency in a non-chemically induced model for insulin-dependent diabetes.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010477:Perfusion; D010765:Phosphorylase Phosphatase / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D006003:Glycogen; D000242:Cyclic AMP; D006005:Phosphorylases; D006006:Glycogen Synthase; D010765:Phosphorylase Phosphatase; D004837:Epinephrine