Inhibition of glycogenolysis by a glucose analogue in the working rat heart.
The effects of BAY o 1248, an inhibitor of alpha-amylo-1, 6-glucosidase, on glycogenolysis and post-ischemic functional recovery were investigated in isolated perfused rat hearts. Working rat hearts were perfused during 30 min with 11 mm glucose (controls) and, in some hearts, with 1 microM insulin or 5 mM lactate to increase their glycogen concentration. The hearts were then submitted to 10 min of no-flow ischemia and reperfused during 15 min with 11 mM glucose alone. Glycogen content was increased by 50% in hearts perfused with insulin or lactate. During ischemia, glycogen breakdown was similar in the control and lactate groups, but was abolished in the insulin-group. At reperfusion, functional recovery was improved in glycogen-loaded hearts compared to controls. When hearts were perfused with 1 mM BAY o 1248, added before ischemia, glycogenolysis was inhibited in the three groups and functional recovery was hampered in both the control and lactate groups. In the insulin group, however, the functional recovery was barely affected by BAY o 1248. We conclude that: (i) BAY o 1248 is an inhibitor of heart glycogen breakdown; (ii) the consequences of inhibition of ischemic glycogenolysis on post-ischemic functional recovery depend on the conditions; and (iii) the protective effect of insulin does not result from ischemic glycogenolysis.
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Hormone and Metabolic Research Unit, Louvain University Medical School, and International Institute of Cellular and Molecular Pathology, Avenue Hippocrate 75, Brussels, B-1200, Belgium.
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D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003864:Depression, Chemical; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D005947:Glucose / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism*; D006004:Glycogen Debranching Enzyme System / Q000037:antagonists & inhibitors; D006321:Heart / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology; D007773:Lactates / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D006004:Glycogen Debranching Enzyme System; D007328:Insulin; D007773:Lactates; D017485:1-Deoxynojirimycin; D006003:Glycogen; C030563:amylo-1,6-glucosidase; D005947:Glucose; D005944:Glucosamine; C045622:emiglitate