Age-dependent changes in metabolism, contractile function, and ischemic sensitivity in hearts from db/db mice.
Glucose and palmitate metabolism and contractile function were measured with ex vivo perfused working hearts from control (db/+) and diabetic (db/db) female mice at 6, 10-12, and 16-18 weeks of age. Palmitate oxidation was increased by 2.2-fold in 6-week-old db/db hearts and remained elevated in 10- to 12- and 16- to 18-week-old hearts. Carbohydrate oxidation was normal at 6 weeks but was reduced to 27 and 23% of control at 10-12 and 16-18 weeks, respectively. At 6 weeks, db/db hearts exhibited a slight reduction in mechanical function, whereas marked signs of dysfunction were evident at 10-12 and 16-18 weeks. Mechanical function after ischemia-reperfusion was examined in hearts from male mice; at 6 weeks, db/db hearts showed normal recovery, whereas at 12 weeks it was markedly reduced. Fatty acid oxidation was the predominant substrate used after reperfusion. Thus, diabetic db/db hearts exhibit signs of a progressive cardiomyopathy; increased fatty acid oxidation preceded reductions in carbohydrate oxidation. Postischemic recovery of function was reduced in db/db hearts, in parallel with age-dependent changes in normoxic contractile performance. Finally, peroxisome proliferator-activated receptor-alpha treatment (3 weeks) did not affect sensitivity to ischemia-reperfusion, even though carbohydrate oxidation was increased and palmitate oxidation was decreased.
Aasum
Ellen
E
Department of Medical Physiology, Faculty of Medicine, University of Tromsoe, Norway. ellenaa@fagmed.uit.no
Hafstad
Anne D
AD
Severson
David L
DL
Larsen
Terje S
TS
D000375:Aging; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D050260:Carbohydrate Metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006321:Heart / Q000254:growth & development* / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009200:Myocardial Contraction / Q000502:physiology*; D017202:Myocardial Ischemia / Q000235:genetics / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size; D010084:Oxidation-Reduction
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin