Study On The Relationship Between Selenium And Diabetes Mellitus

Diabetes mellitus is one of the main threats to human health in the 21st century. Due to the deterioration of environment and changes in human behaviour and lifestyle, the past two decades have seen an explosive increase in the number of people diagnosed with diabetes in developing countries as well as in developed countries.Selenium is an essential trace element, which functions as an antioxidant and anticancer agent. Recently, it has been found that selenium has another function: an insulin-mimetic, which enhances glucose transport, intervenes glucose metabolism and mimics insulin signal transduction. In the investigations about the relationship of selenium and diabetes, the effective hypoglycemic doses of selenium administration reported were quite different from each other. Much research concentrated on the role of Se on the classical targets of insulin, such as adipocyte, hepatocyte and muscle cell, but seldom on the role of Se in brain, also one of the important targets of insuin. And the influence of Se on pancreatic islets was rarely involved in the literature, either. Study on the mentioned questions will help to further understand the relationship between Se and diabetes mellitus, and probably provide some information for the research and development of new antidiabetic drugs.Therefore, this paper focused on the in vivo and in vitro investigation of the above puzzling points in the relationship between Se and diabetes mellitus, which got the following main results.1. An effective hypoglycemic dose of oral selenite administrationThe study of the low, medium and high dose of selenite administrations on the alloxan-induced diabetic Kunming mice revealed that the low dose of selenite 80μg·kg-1·day-1(ig)had no impact on the hyperglycemia, but the medium dose of selenite 2 mg·kg-1·day-1(ig)could effectively reduce hyperglycemia in two weeks of treatment. The high dose of selenite 4 mg·kg-1·day-1(ig)showed the hypoglycemic effect on the diabetic mice at the initial treatment, but this hypoglycemic effect could not last for a week. In the experiment of the high dose of selenite administration, it was also found that alloxan induced diabetes could not arouse the changes of Se levels in plasma and the tissues of liver, kidney, spleen and brain while selenite treatment was beneficial to the antioxidant system in the blood of diabetic mice.2. A new diabetic animal model and observation on the relation of the changes of Se levels in plasma to the duration of diabetes Three consecutive intraperitoneal injections of alloxan(100 mg·kg-1)in rats induced two types of diabetic models: the typical typeⅠdiabetic model, of which the animal showed hyperglycemia regardless of when non-fasted or overnight fasted; the sub-typeⅠdiabetic model (temporal denomination), of which the diabetic animal showed hyperglycemia only when non-fasted while the hyperglycemia returned to normaglycemia when overnight fasted. Meanwhile, it was found that alloxan could give rise to hyperinsulinemia in the development of alloxan-induced diabetes on rats, suggesting that alloxan could induce insulin resistance on rats when used to produce a diabetic model. And more, alloxan could cause inflammatory infiltration into pancreatic islets, implying that immune toxicity might be involved in the mechanism of alloxan toxicity to β-cells though reactive oxygen species have been found to take part in the process of β-cell death caused by alloxan.3. The influence of Se on the important biological molecule, GSHThe study found that alloxan could decrease the GSH levels in the blood and the tissues of liver, kidney and testis of mice while, selenite treatment for 4 weeks (2 mg·kg-1·day-1) could counteract the decreases in GSH levels in mice and increase GSH level in brain of the diabetic mice, compared to the normal control. One of reasons of the increase of GSH in diabetic liver by the selenite treatment might be that selenite supplement could increase the activity of glutathione reductase and reduce the activity of glutathione-s-...