Testosterone Combined with Voluntary Exercise Attenuates Diabetes-induced Pancreatic Apoptosis in Castrated Diabetic Rats Induced by HFD/STZ

Abstract Increased apoptosis in the pancreas and beta cell death causes reduced insulin secretion in type 2 diabetes. This study was aimed to evaluate the effects of exercise training and testosterone administration on apoptosis marker (p53 protein) in the pancreas tissue in animal with diabetes. Type 2 diabetes was induced by high fat diet and injection of low dose STZ (35mg/kg; ip). After 2 months of treatment with testosterone (2mg/kg/day) or voluntary exercise alone or in combination, apoptosis (tunnel assay) and p53 protein (ELISA method) were measured. Testosterone and exercise decreased the blood glucose, HbA1c levels, HOMA-IR, p53 protein expression and increased insulin level in treated diabetic and diabetic castrated groups. Simultaneous treatment of these groups with testosterone together voluntary exercise had an additive effect on reducing p53 expression, blood glucose, HbA1c levels, HOMA-IR and subsequently decreasing apoptosis. Our results suggest that the apoptosis decreasing effect of testosterone and voluntary exercise is associated with the reduced levels of blood glucose, HbA1c and HOMA-IR that subsequently decreased the expression of p53 level.

Cardioprotective Effect of Crocin Combined with Voluntary Exercise in Rat: Role of Mir-126 and Mir-210 in Heart Angiogenesis / Efeito Cardioprotetor de Crocina Combinado com Exercício Voluntário em Ratos: Papel do Mir-126 e Mir-210 na Angiogênese Cardíaca

Abstract Background: Crocin is reported to have a wide range of biological activities such as cardiovascular protection. Recent epidemiologic studies have shown that exercise reduces cardiovascular morbidity and mortality in the general population. Objective: The aim of this study was to evaluate the effect of crocin and voluntary exercise on miR-126 and miR-210 expression levels and angiogenesis in the heart tissue. Methods: Animals were divided into 4 groups: control, exercise, crocin, and exercise-crocin. Animals received oral administration of crocin (50 mg/kg) or performed voluntary exercise alone or together for 8 weeks. Akt, ERK1/2 protein levels, miR-126 and miR-210 expression were measured in the heart tissue. Immunohistochemical method was used to detect CD31 in the heart tissue. Results: Akt and ERK1/2 levels of the heart tissue were higher in crocin treated group and voluntary exercise trained group after 8 weeks. Combination of crocin and exercise also significantly enhanced Akt and ERK1/2 levels in the heart tissue. MiR-126, miR-210 expression and CD31 in the heart increased in both crocin and voluntary exercise groups compared with control group. In addition, combination of exercise and crocin amplified their effect on miR-126 and miR-210 expression, and angiogenesis. Conclusion: Crocin and voluntary exercise improve heart angiogenesis possibly through enhancement of miR-126 and miR-210 expression. Voluntary exercise and diet supplementation with crocin could have beneficial effects in prevention of cardiovascular disease.

Resumo Fundamentos: A crocina tem uma vasta gama de atividades biológicas, tais como a proteção cardiovascular. Estudos epidemiológicos recentes demonstraram que o exercício reduz a morbidade e a mortalidade cardiovasculares na população em geral. Objetivo: O objetivo deste estudo foi avaliar o efeito da crocina e do exercício voluntário nos níveis de expressão miR-126 e miR-210 e na angiogênese no tecido cardíaco. Métodos: Os animais foram divididos em 4 grupos: controle, exercício, crocina e exercício-crocina. Os animais receberam a administração oral de crocina (50 mg/kg) ou realizaram exercício voluntário sozinhos ou em conjunto durante 8 semanas. Os níveis de proteína Akt, ERK1/2, e a expressão de miR-126 e miR-210 foram medidos no tecido cardíaco. O método imunohistoquímico foi utilizado para detectar CD31 no tecido cardíaco. Resultados: Os níveis de Akt e ERK1/2 do tecido cardíaco foram maiores no grupo tratado com crocina e no grupo de exercício voluntário após 8 semanas. A combinação de crocina e exercício também aumentou significativamente os níveis de Akt e ERK1/2 no tecido cardíaco. A expressão de MiR-126, miR-210 e CD31 no coração aumentou tanto em no grupo de crocina como no grupo de exercício voluntário em comparação com o grupo de controle. Além disso, a combinação de exercício e crocina amplificou seu efeito na expressão de miR-126 e miR-210 e angiogênese. Conclusão: A Crocina e o exercício voluntário melhoram a angiogênese cardíaca possivelmente através do aumento da expressão de miR-126 e miR-210. O exercício voluntário e a suplementação dietética com crocina podem ter efeitos benéficos na prevenção de doenças cardiovasculares.