Diabetes and mitochondrial oxidative stress: A study using heart mitochondria from the diabetic Goto-Kakizaki rat

Santos, Dario L.; Palmeira, Carlos M.; Seiça, Raquel; Dias, José Maria Moreira; Mesquita, J. F.; Moreno, António J.; Santos, Maria S.

doi:10.1007/978-1-4615-0298-2_23

Cited by 34 publications

(42 citation statements)

References 43 publications

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“…The inner mitochondrial membrane is believed to be particularly susceptible to oxidative damage even under physiological conditions, for it is a major site where ROS, and a high content of polyunsaturated fatty acids, accumulate and react with each other, thus yielding a large amount of stronger lipid peroxidation products which incur alterations in the structure integrity of mitochondrial membranes, causing irreversible swelling and disruption. A previous study demonstrated that oxidative stress induced in vitro by ADP-Fe 2+ in mitochondria strongly initiated a significant increase of lipid peroxidation (measured by O 2 consumption and thiobarbituric acid reactive species formation) and concurrent increase of mitochondria volume [20] . Another study proves that antioxidative agents such as Ginkgo biloba extract (EGb 761) succeeds in protecting mitochondria in cells of liver and heart from enlarging using diabetic model animals [20,21] .…”

Section: Discussionmentioning

confidence: 96%

“…A previous study demonstrated that oxidative stress induced in vitro by ADP-Fe 2+ in mitochondria strongly initiated a significant increase of lipid peroxidation (measured by O 2 consumption and thiobarbituric acid reactive species formation) and concurrent increase of mitochondria volume [20] . Another study proves that antioxidative agents such as Ginkgo biloba extract (EGb 761) succeeds in protecting mitochondria in cells of liver and heart from enlarging using diabetic model animals [20,21] . Ang II increases NADPH oxidase activity and decreases NO levels, and both lead to aggravation of oxidative stress.…”

Section: Discussionmentioning

confidence: 96%

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Angiotensin II receptor blocker provides pancreatic ?-cell protection independent of blood pressure lowering in diabetic db/db mice

Shao

Iwashita

et al. 2007

Acta Pharmacologica Sinica

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Aim: Several epidemiological studies have suggested that treatment with angiotensin II type 1 receptor blocker provided a risk reduction of developing type 2 diabetes. The aim of this study was to investigate whether and how chronic candesartan treatment can attenuate the deleterious influence of the hyperactive local intra‐islet renin‐angiotensin system in the diabetes state. Methods: Eight‐week‐old db/db mice were randomized to candesartan 1 mg/kg, candesartan 10 mg/kg, manidipine 10 mg/kg, or placebo via gavage for 6 weeks. Their age‐matched nondiabetic littermates db/m mice were treated with placebo and acted as nondiabetic controls. After 6 weeks’treatment, an intraperitoneal glucose tolerance test, immunohistochemical staining of oxidative stress markers, insulin, CD31, azan staining and an electron microscopy observation were performed. Results: Chronic candesartan treatment provided an improvement of glucose tolerance, and greatly rescued islet β‐cell mass. Candesartan treatment also notably decreased staining intensity of oxidative stress markers, as well as attenuating intra‐islet fibrosis and improving blood supply in the islet. In the electron microscopy observation, candesartan‐treated animals exhibited improved granulation and less remarkable endoplasmic reticulum and Golgi bodies; furthermore, candesartan treatment greatly relieved the swelling of mitochondria to nearly normal. Both the benefits of reducing oxidative stress and ultrastructure protection were in a dose‐dependent and blood pressure‐independent manner. Conclusion: After diabetes was initiated, candesartan treatment could not reverse the state of diabetes, but it effectively improved glucose tolerance and protected β‐cell function by attenuating oxidative stress, islet fibrosis, sparsity of blood supply and ultrastructure disruption in a dose‐dependent and blood pressure‐independent manner.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Angiotensin II receptor blocker provides pancreatic ?-cell protection independent of blood pressure lowering in diabetic db/db mice

Shao

Iwashita

et al. 2007

Acta Pharmacologica Sinica

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“…In recent years there has been increasing interest in the mitochondrion as numerous important physiological functions and disorders have been linked to this organelle (1)(2)(3). Malfunctioning mitochondrial metabolism is known to play a role not only in rare childhood diseases but also in many leading causes of death including heart disease, diabetes, and Parkinson's disease.…”

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confidence: 99%

Reconstruction and Functional Characterization of the Human Mitochondrial Metabolic Network Based on Proteomic and Biochemical Data

Greenberg

Palsson

2004

Journal of Biological Chemistry

140

125

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Diverse datasets including genomic, proteomic, isotopomer, and DNA sequence variation are becoming available for human mitochondria. Thus there is a need to integrate these data within an in silico modeling framework where mitochondrial biology and related disorders can be studied and analyzed. This paper reports a reconstruction and characterization of the human mitochondrial metabolic network based on proteomic and biochemical data. The 189 reactions included in this reconstruction are both elementally and charge-balanced and are assigned to their respective cellular compartments (mitochondrial, cytosol, or extracellular). The capabilities of the reconstructed network to fulfill three metabolic functions (ATP production, heme synthesis, and mixed phospholipid synthesis) were determined. Network-based analysis of the mitochondrial energy conversion process showed that the overall ATP yield per glucose is 31.5. Network flexibility, characterized by allowable variation in reaction fluxes, was evaluated using flux variability analysis and analysis of all of the possible optimal flux distributions. Results showed that the network has high flexibility for the biosynthesis of heme and phospholipids but modest flexibility for maximal ATP production. A subset of all of the optimal network flux distributions, computed with respect to the three metabolic functions individually, was found to be highly correlated, suggesting that this set may contain physiological meaningful fluxes. Examinations of optimal flux distributions also identified correlated reaction sets that form functional modules in the network.In recent years there has been increasing interest in the mitochondrion as numerous important physiological functions and disorders have been linked to this organelle (1-3). Malfunctioning mitochondrial metabolism is known to play a role not only in rare childhood diseases but also in many leading causes of death including heart disease, diabetes, and Parkinson's disease. The human mitochondrial genome was one of the first genomes to be sequenced (4), and more recently, the proteome of the human cardiac mitochondrion has been identified in two separate studies (5, 6). The analyses of mitochondrial proteomic and isotopomer data have proven to be useful in detecting the onset of cancer and studying glucose homeostasis in diabetes (7,8). With the increasing availability of these independent datasets, there is a growing need for incorporating and reconciling such information in a genetically and biochemically consistent format. We have developed a constraint-based model of the human cardiac mitochondrion to meet this need.The constraint-based approach for analyzing reconstructed networks involves the application of a series of constraints arising from reaction stoichiometry, thermodynamics, enzymatic capacities, and regulatory and kinetic constraints when they are available (9, 10). Using this approach, a variety of methods including flux balance analysis (11, 12), extreme pathway analysis (13,14), and mixed integer linear...

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“…MPTP induction would not be hindered by the increased amount of vitamin E, whose main role would be to decrease lipid peroxidation, but not oxidative phenomena that lead to MPTP opening. As proposed in previous published works [13,14], the increased oxidative stress observed in diabetic rats is probably contributing to an adaptive increase in mitochondrial amounts of coenzyme Q and vitamin E. A recent investigation done in the heart mitochondria from GK rats showed a lower amount of coenzyme Q9 [16]. This was suggested to be responsible for an increased susceptibility of diabetic heart mitochondria to oxidative damage.…”

Section: Discussionmentioning

confidence: 60%

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

Oliveira

Esteves

Seiça

et al. 2004

Diabetes Metabolism Res

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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.

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Diabetes and mitochondrial oxidative stress: A study using heart mitochondria from the diabetic Goto-Kakizaki rat

Cited by 34 publications

References 43 publications

Angiotensin II receptor blocker provides pancreatic ?-cell protection independent of blood pressure lowering in diabetic db/db mice

Angiotensin II receptor blocker provides pancreatic ?-cell protection independent of blood pressure lowering in diabetic db/db mice

Reconstruction and Functional Characterization of the Human Mitochondrial Metabolic Network Based on Proteomic and Biochemical Data

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

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