title: Glucose and insulin improve cardiac efficiency and postischemic functional recovery in perfused hearts from type 2 diabetic (db/db) mice.
abstract: Hearts from type 2 diabetic (db/db) mice demonstrate altered substrate utilization with high rates of fatty acid oxidation, decreased functional recovery following ischemia, and reduced cardiac efficiency. Although db/db mice show overall insulin resistance in vivo, we recently reported that insulin induces a marked shift toward glucose oxidation in isolated perfused db/db hearts. We hypothesize that such a shift in metabolism should improve cardiac efficiency and consequently increase functional recovery following low-flow ischemia. Hearts from db/db and nondiabetic (db/+) mice were perfused with 0.7 mM palmitate plus either 5 mM glucose (G), 5 mM glucose and 300 microU/ml insulin (GI), or 33 mM glucose and 900 microU/ml insulin (HGHI). Substrate oxidation and postischemic recovery were only moderately affected by GI and HGHI in db/+ hearts. In contrast, GI and particularly HGHI markedly increased glucose oxidation and improved postischemic functional recovery in db/db hearts. Cardiac efficiency was significantly improved in db/db, but not in db/+ hearts, in the presence of HGHI. In conclusion, insulin and glucose normalize cardiac metabolism, restore efficiency, and improve postischemic recovery in type 2 diabetic mouse hearts. These findings may in part explain the beneficial effect of glucose-insulin-potassium therapy in diabetic patients with cardiac complications.
authors.affiliation: Department of Medical Physiology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Tromsø, Norway. anned@fagmed.uit.no
authors.forename: Anne D
authors.initials: AD
authors.lastname: Hafstad
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Khalid
authors.forename: Ole-Jakob
authors.initials: OJ
authors.lastname: How
authors.forename: Terje S
authors.initials: TS
authors.lastname: Larsen
authors.forename: Ellen
authors.initials: E
authors.lastname: Aasum
mesh_terms: D000818:Animals; D001011:Aorta / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010168:Palmitates / Q000494:pharmacology; D012044:Regression Analysis; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D007328:Insulin; D010168:Palmitates; D005947:Glucose