Reduced high-energy phosphate levels in rat hearts. I. Effects of alloxan diabetes.
Significant alterations in heart carbohydrate and lipid metabolism are present 48 h after intravenous injection of alloxan (60 mg/kg) in rats. It has been suggested that uncoupling of oxidative phosphorylation occurs in the alloxanized rat heart in vivo, whereas normal oxidative metabolism has been demonstrated in alloxan-diabetic rat hearts perfused in vitro under conditions of adequate oxygen delivery. We examined the hypothesis that high-energy phosphate metabolism might be adversely affected in the alloxan-diabetic rat heart in vivo. Phosphocreatine and ATP were reduced by 58 and 45%, respectively (P is less than 0.001). Also, oxygen-dissociation curves were shifted to the left by 4 mmHg, and the rate of oxygen release from blood was reduced by 21% (P is less than 0.01). Insulin administration normalized heart high-energy phosphate compounds. ATP production was accelerated in diabetic hearts perfused in vitro with a well-oxygenated buffer. These studies support the hypothesis that oxidative ATP production in the alloxan-diabetic rat heart is reduced and suggest that decreased oxygen delivery may have a regulatory role in the oxidative metabolism of the diabetic rat heart.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose; D001794:Blood Pressure; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D016883:Diabetic Ketoacidosis; D004163:Diphosphoglyceric Acids / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D004986:Ether; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005958:Glucosephosphates / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006339:Heart Rate; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000097:blood / Q000494:pharmacology; D010424:Pentobarbital; D010725:Phosphocreatine / Q000378:metabolism*; D051381:Rats
D001786:Blood Glucose; D004163:Diphosphoglyceric Acids; D005230:Fatty Acids, Nonesterified; D005958:Glucosephosphates; D007328:Insulin; D010725:Phosphocreatine; D004986:Ether; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006003:Glycogen; D010424:Pentobarbital; D010100:Oxygen