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.
BACKGROUND:Renal disease associated with diabetes mellitus is a major problem among diabeticpatients. 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.
Authors: Melinda T Coughlan; David R Thorburn; Sally A Penfold; Adrienne Laskowski; Brooke E Harcourt; Karly C Sourris; Adeline L Y Tan; Kei Fukami; Vicki Thallas-Bonke; Peter P Nawroth; Michael Brownlee; Angelika Bierhaus; Mark E Cooper; Josephine M Forbes Journal: J Am Soc Nephrol Date: 2009-01-21 Impact factor: 10.121
Authors: Gonçalo C Pereira; Susana P Pereira; Claudia V Pereira; José A Lumini; José Magalhães; António Ascensão; Maria S Santos; António J Moreno; Paulo J Oliveira Journal: PLoS One Date: 2012-06-22 Impact factor: 3.240