Alterations of liver mitochondrial bioenergetics in diabetic Goto-Kakizakirats

Respiratory indexes and the transmembrane electrical potential (Delta Psi) were evaluated in mitochondrial preparations from 6-month-old Goto-Kakizaki (GK) and Wistar rats in the presence of glutamate + malate and succinate. We found that in diabetic GK mitochondria, flavin adenine dinucleotide (FAD )-linked respiratory indexes (respiratory control ratio [RCR] and adenosine diphosphate [ADP] to oxygen ratio [ADP/O]) are increased and uncoupled res piration is largely enhanced, indicating increased respiratory chain activi ty in GK rats. Delta Psi development in GK mitochondrial preparations, ener gized using glutamate + malate or succinate as substrates, and the repolari zation rate upon phosphorylation of the added ADP were significantly higher in GK mitochondrial preparations. These results indicate an enhanced activ ity of the phosphorylation system, confirmed by evaluating Delta Psi develo pment when the mitochondria are energized by adenosine triphosphate (ATP), Moreover, recovery of the potential upon a phosphorylative cycle is increas ed in GK mitochondria, reflecting a more efficient coupling between the pho sphorylative and oxidative system. Contrasting with results obtained for al loxan- or streptozotocin-induced diabetic rats, this study clearly demonstr ates no impairment of mitochondrial bioenergetics in diabetic GK rats. On t he contrary, at this age, we observed a higher efficiency of the phosphoryl ation system as compared with Wistar rats. Copyright (C) 1999 by W.B. Saund ers Company.