Age-related alterations in liver mitochondrial bioenergetics of diabetic Goto-Hakizaki rats

Type 2 diabetes mellitus is one of the most common chronic metabolic diseas es in man. Due to long-term complications of the disease, severely decreasi ng the quality of life of diabetic patients, early interventions to obviate the risk of complications are of major importance. Therefore, diabetic ani mal models are of major importance in research for interventional treatment of type 2 diabetes. In this work we investigated the possible alterations in mitochondrial ener getic metabolism of Goto-Kakizaki (GK) rats during the progression of the d isease, since glucose metabolism is closely related to intracellular ATP co ntent. For that reason, respiratory indexes (state 4, state 3, RCR and ADP/ O) were evaluated either in the presence of NAD- or FAD-linked substrates ( glutamate + malate and succinate, respectively) in mitochondrial preparatio ns of GK and control rats with 8, 12, 26 and 52 weeks of age. Until the age of 1 year (52 weeks) we found no impairment of mitochondrial respiratory i ndexes both in the presence of glutamate + malate and succinate. In conclus ion, this study indicates that GK rat is a good model for studying the init ial events of diabetes, since it presents no impairment of liver mitochondr ial functions during the first year of life, contrasting clearly with pharm acological induced diabetes.