Protective effect of testosterone on early apoptotic damage induced by streptozotocin in rat pancreas

Abstract

Beta-cell apoptosis is responsible for the development of insulin-dependent diabetes mellitus in the streptozotocin (STZ) rat model. It has been demonstrated that steroid hormones possess antioxidant and protective antiapoptotic effects in many tissues. The aim of the present study was to investigate the early apoptotic damage induced by STZ in rat pancreas, and the effect of testosterone in preventing apoptosis of pancreatic cells. Intact and castrated adult male Wistar rats were subjected to a unique injection of STZ 60 mg/kg (body weight) in citrate buffer, and the kinetics of apoptosis in cells was assessed. Insulin and glucose were measured by RIA and a glucometer respectively, and in pancreatic tissue by immunohistochemistry. At 6 h after STZ injection, a marked increase in apoptotic cells was detected; however, glucose and insulin serum levels were not significantly different from the controls. The castrated animals presented higher percentages of apoptotic cells (65·75 5·42%) than intact males (20·6 4·38%) and castrated, testosterone-substituted males (30·66 1·38%). The decrease in apoptotic cells induced by testosterone was reversed by the antiandrogen flutamide (67·69 3·45%). The overall results indicate that early apoptotic damage produced by STZ in castrated animals was reversed by testosterone, suggesting that this hormone exerts a natural protective effect in rat pancreas. This effect could help to explain some sexual differences in diabetes mellitus incidence in man, reinforcing the idea that new approaches in steroid hormone therapies should be considered for treatment of this disease.

The pancreatic β-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes

“…After 4 weeks of diabetes, females show less and smaller pancreatic islets, and less serum insulin than control females and diabetic males; indeed diabetic females have higher blood glucose values and lower survival rates than diabetic males (Vital et al, 2006). This is in accordance with the action of testosterone in protecting -cells from STZ-induced apoptosis (Morimoto et al, 2005). More research is warranted in this area to solve the gender differences that apparently exist between mice and rats.…”

1α,25 Dihydroxyvitamin D3: Therapeutic and Preventive Effects against Oxidative Stress, Hepatic, Pancreatic and Renal Injury in Alloxan-Induced Diabetes in Rats

“…Other mechanisms have been proposed to explain the antioxidant property of 1␣,25(OH)2VD3 as i) induction of glucose-6-phosphate dehydrogenase (G6PD) gene expression, a key antioxidant enzyme (36); ii) increase in estrogen and testosterone levels (33) which are essentials in the regulation of insulin secretion and the modulation of the insulin receptors (38,39). All these beneficial effects of 1␣,25(OH)2VD3 against hepatic and renal toxicity are supported by the lower rate in lipid peroxidation and the hepatic (AST, ALT, PAL, total and direct bilirubin rate) and renal (creatinine and urea levels) levels of toxicity.…”

Impaired expression of sex hormone receptors in male reproductive organs of diabetic rat in response to oral antidiabetic drugs

“…The reported testicular changes of streptozotocin (STZ)-induced diabetic rats are not caused by a direct effect of STZ, but by diabetes itself [3]. Therefore, STZ-induced diabetes in rats is used as a model for studying effects of diabetes on various body organs [4,5]. A closer look into fertility rates of modern societies reveals that the increased incidence of DM has been closely associated with falling birth rates and fertility [6,7].…”