title: Attenuation of Ca2+ homeostasis, oxidative stress, and mitochondrial dysfunctions in diabetic rat heart: insulin therapy or aerobic exercise?
abstract: We tested the effects of swimming training and insulin therapy, either alone or in combination, on the intracellular calcium ([Ca(2+)]i) homeostasis, oxidative stress, and mitochondrial functions in diabetic rat hearts. Male Wistar rats were separated into control, diabetic, or diabetic plus insulin groups. Type 1 diabetes mellitus was induced by streptozotocin (STZ). Insulin-treated groups received 1 to 4 UI of insulin daily for 8 wk. Each group was divided into sedentary or exercised rats. Trained groups were submitted to swimming (90 min/day, 5 days/wk, 8 wk). [Ca(2+)]i transient in left ventricular myocytes (LVM), oxidative stress in LV tissue, and mitochondrial functions in the heart were assessed. Diabetes reduced the amplitude and prolonged the times to peak and to half decay of the [Ca(2+)]i transient in LVM, increased NADPH oxidase-4 (Nox-4) expression, decreased superoxide dismutase (SOD), and increased carbonyl protein contents in LV tissue. In isolated mitochondria, diabetes increased Ca(2+) uptake, susceptibility to permeability transition pore (MPTP) opening, uncoupling protein-2 (UCP-2) expression, and oxygen consumption but reduced H2O2 release. Swimming training corrected the time course of the [Ca(2+)]i transient, UCP-2 expression, and mitochondrial Ca(2+) uptake. Insulin replacement further normalized [Ca(2+)]i transient amplitude, Nox-4 expression, and carbonyl content. Alongside these benefits, the combination of both therapies restored the LV tissue SOD and mitochondrial O2 consumption, H2O2 release, and MPTP opening. In conclusion, the combination of swimming training with insulin replacement was more effective in attenuating intracellular Ca(2+) disruptions, oxidative stress, and mitochondrial dysfunctions in STZ-induced diabetic rat hearts.
authors.affiliation: Departments of General Biology and.
authors.forename: Márcia F
authors.initials: MF
authors.lastname: da Silva
authors.affiliation: Physical Education, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil;
authors.forename: Antônio J
authors.initials: AJ
authors.lastname: Natali
authors.affiliation: Departments of General Biology and Department of Basic Sciences, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, Minas Gerais, Brazil; and.
authors.forename: Edson
authors.initials: E
authors.lastname: da Silva
authors.affiliation: Physical Education, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil;
authors.forename: Gilton J
authors.initials: GJ
authors.lastname: Gomes
authors.affiliation: Department of Physics and Chemistry, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Bruno G
authors.initials: BG
authors.lastname: Teodoro
authors.affiliation: Physical Education, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil;
authors.forename: Daise N Q
authors.initials: DN
authors.lastname: Cunha
authors.affiliation: Physical Education, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil;
authors.forename: Lucas R
authors.initials: LR
authors.lastname: Drummond
authors.affiliation: Physical Education, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil;
authors.forename: Filipe R
authors.initials: FR
authors.lastname: Drummond
authors.affiliation: Physical Education, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil;
authors.forename: Anselmo G
authors.initials: AG
authors.lastname: Moura
authors.affiliation: Physical Education, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil;
authors.forename: Felipe G
authors.initials: FG
authors.lastname: Belfort
authors.affiliation: Physical Education, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil;
authors.forename: Alessandro
authors.initials: A
authors.lastname: de Oliveira
authors.affiliation: Departments of General Biology and.
authors.forename: Izabel R S C
authors.initials: IR
authors.lastname: Maldonado
authors.affiliation: Department of Physics and Chemistry, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil alberici@fcfrp.usp.br.
authors.forename: Luciane C
authors.initials: LC
authors.lastname: Alberici
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007473:Ion Channels; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D024101:Mitochondrial Proteins; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013550:Swimming / Q000502:physiology; D000071246:Uncoupling Protein 2
chemical_list: D007328:Insulin; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; D010100:Oxygen; D002118:Calcium
keywords: Nox-4; diabetes mellitus; mitochondria; physical activity