Hyperglycemia does not alter state 3 respiration in cardiac mitochondria from type-I diabetic rats.
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| Abstract |
Cardiovascular complications are the primary cause of death for diabetic patients. Clinically, the development of dysfunctional cardiomyopathy is one of the main complications of diabetes. Experimental evidence indicates that the mitochondrion is one of the main sites implicated in the development of cardiac dysfunction. Yet, the precise cause and mechanisms involved in the process are largely debated. We report here that heart mitochondria from streptozotocin-induced diabetic Sprague-Dawley rats present a gradual reduction in state 3 oxygen consumption that reaches 35% by the fourth week following diabetes onset. Rats presenting a level of hyperglycemia similar to diabetic animals, but not showing the marked weight loss or appearance of urinary ketones typical of the later group present no decline in state 3 mitochondrial oxygen consumption, the values being indistinguishable from those of mitochondria from control animals. Mitochondria from hyperglycemic non-ketotic rats, however, show a 15-20% increase in state 4 respiration, but only when glutamate is used as energetic substrate. Mitochondria from diabetic rats, instead, show a 40-50% increase in state 4 respiration with glutamate and 20-25% with succinate as energetic substrate. Interestingly, hyperglycemic non-ketotic animals present a level of serum insulin intermediate between those of controls and diabetic animals. These functional modifications are unrelated to the time elapsed since the onset of diabetes, as they are observed at 2, 4, 6 as well as 8 and 12 weeks after diabetes onset. Taken together, these data argue against hyperglycemia per se being a direct cause of the decline in state 3 oxygen consumption observed in cardiac mitochondria of type-I diabetic rats. Rather, they point to insulin level and subsequent metabolic alterations as a possible cause for the insurgence of mitochondrial dysfunction.
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| Authors | Ossama Lashin, Andrea Romani |
| Journal | Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 267 Issue 1-2 Pg. 31-7 (Dec 2004) ISSN: 0300-8177 [Print] Netherlands |
| PMID | 15663183 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.) |
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