DIABETES/METABOLISM RESEARCH AND REVIEWS RESEARCH ARTICLE Diabetes Metab Res Rev 2004; 20: 131–136. Published online 5 January 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/dmrr.423 Calcium-dependent mitochondrial permeability transition is augmented in the kidney of Goto-Kakizaki diabetic rat Paulo J. Oliveira 1 * Telma C. Esteves 1,2 Raquel Sei¸ ca 3 Ant´ onio J. M. Moreno 1 Maria S. Santos 1 1 Centro de Neurociˆ encias de Coimbra, Departamento de Zoologia, Faculdade de Ciˆ encias e Tecnologia, Universidade de Coimbra, Portugal 2 Departamento de Biologia Vegetal, Faculdade de Ciˆ encias, Universidade de Lisboa, Portugal 3 Faculdade de Medicina, Centro de Neurociˆ encias de Coimbra, Universidade de Coimbra, Portugal *Correspondence to: Paulo J. Oliveira, Centro de Neurociˆ encias de Coimbra, Departamento de Zoologia, Universidade de Coimbra, P-3004-517 Coimbra, Portugal. E-mail: pauloliv@ci.uc.pt Received: 24 April 2003 Revised: 1 August 2003 Accepted: 6 October 2003 Abstract Background Renal disease associated with diabetes mellitus is a major problem among diabetic patients. The role of mitochondria in the pathogenesis of diabetes has received a large amount of attention in the last years, but many aspects of this subject are still poorly understood. In the present study, we studied the susceptibility of the mitochondrial permeability transition (MPT) on kidney mitochondria from the Goto-Kakizaki (GK) rat, an animal model featuring physiological and pathological alterations characteristic of type 2 diabetes. Methods Kidney mitochondria were isolated by differential centrifugations; mitochondrial electric transmembrane potential and calcium loading capacity were evaluated with a TPP + -selective electrode and with a calcium-sensitive fluorescent probe. Coenzyme Q9, Q10 and vitamin E were evaluated by high-performance liquid chromatography (HPLC). Results Kidney mitochondria from the diabetic animals had an increased susceptibility to the induction of the MPT by calcium. We observed a loss of calcium-loading capacity and a higher calcium-induced mitochondrial depolarization. Vitamin E and coenzyme Q9 were also increased in kidney mitochondria from GK rats. Conclusions The results show an enhanced MPT activation in kidney mitochondria from GK rats, which lead us to suggest that this condition may be one major alteration triggered by chronic diabetes in kidney cells, ultimately leading to cell dysfunction. Copyright  2004 John Wiley & Sons, Ltd. Keywords mitochondrial permeability transition; kidney mitochondria; type 2 diabetes; Goto-Kakizaki rat Introduction Type 2 diabetes is the most common type of diabetes nowadays, accounting for nearly 90% of all known cases. Among other complications, diabetes mellitus–associated renal disease is a major concern among diabetic patients [1,2]. Knowledge about the nature of the mitochondrial permeability transition (MPT) and its precise physiological and pathological role in a chronic dis- ease such as type 2 diabetes is scarce. Relating to kidney mitochondria, the information regarding MPT induction is totally unavailable. The MPT is Copyright  2004 John Wiley & Sons, Ltd.