Cardiac mitochondrial alterations observed in hyperglycaemic rats--what can we learn from cell biology?
Diabetes mellitus is one of the most common metabolic diseases in the world. The complications associated with this disease are often responsible for a decreased quality of life in many patients. For example, the diabetic population has a greater probability to suffer from cardiovascular problems and heart failure than the general population. Due to the importance heart mitochondria have in the context of the bioenergetics of the myocardium, it appears logical to explore mitochondrial dysfunction as an important link between hyperglycaemia and heart alterations observed during diabetes. One important factor that can lead to mitochondrial dysfunction is the mitochondrial permeability transition (MPT), caused by the formation of poly-protein pores (MPT pores), occurring with mitochondrial calcium overload and increased oxidative stress, conditions already described to exist in myocytes exposed to hyperglycaemia. The MPT has been involved as determinant in the survival of myocytes after anoxia and reoxigenation, as well as in triggering cell death. The present review deals with cardiac mitochondrial alterations observed in drug-induced hyperglycaemic animals or in the GK rat, a hereditary model of hyperglycaemia. Respiration rates, susceptibility to oxidative stress, protein expression and MPT induction are altered in hyperglycaemic animals, which in extreme conditions can alter the bioenergetics of the diabetic myocardium and even cause myocardial cell death. The study of the cardiac mitochondrial function of hyperglycaemic animals offer an important insight, not only to explain cardiac alterations found in diabetic patients, but also in the design of new therapeutic approaches to reduce mitochondrial dysfunction and cell death typically associated with diabetes.
Oliveira
Paulo J
PJ
Center for Neurosciences and Cellular Biology of Coimbra, Department of Zoology, University of Coimbra, P-3004-517 Coimbra, Portugal. pauloliv@ci.uc.pt
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D006943:Hyperglycemia / Q000503:physiopathology*; D008929:Mitochondria, Heart / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology; D051336:Mitochondrial Membranes / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D009210:Myofibrils / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000502:physiology
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D015221:Potassium Channels