Calcium-dependent mitochondrial permeability transition is augmented in the kidney of Goto-Kakizaki diabetic rat

• Published in: Diabetes/metabolism research and reviews Vol. 20; no. 2; pp. 131 - 136
• Main Authors: Oliveira, Paulo J., Esteves, Telma C., Seiça, Raquel, Moreno, António J. M., Santos, Maria S.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.03.2004; Wiley
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Calcium - metabolism; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - complications; Diabetic Nephropathies - metabolism; Disease Models, Animal; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Goto-Kakizaki rat; Intracellular Membranes - metabolism; Kidney Diseases - etiology; Kidney Diseases - metabolism; kidney mitochondria; Male; Medical sciences; Membrane Potentials - physiology; Mitochondria - metabolism; mitochondrial permeability transition; Permeability; Rats; Rats, Inbred Strains; Rats, Wistar; Reference Values; type 2 diabetes; Ubiquinone - metabolism; Vitamin E - metabolism; Endocrinopathy; Type 2 diabetes; Animal model; Mitochondria; Goto-Kakizaki rat; Calcium; kidney mitochondria; mitochondrial permeability transition; Permeability; Inorganic element; Kidney; Goto Kakizaki rat
• ISSN: 1520-7552; 1520-7560
• DOI: 10.1002/dmrr.423

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.