Abstract
Females live longer than males, and the estrogens are one of the reasons for this difference. We reported some years ago that estrogens are able to protect rats against oxidative stress, by inducing antioxidant genes. Type 2 diabetes is an age-associated disease in which oxidative stress is involved, and moreover, some studies show that the prevalence is higher in men than in women, and therefore there are sex-associated differences. Thus, the aim of this study was to evaluate the role of estrogens in protecting against oxidative stress in type 2 diabetic males and females. For this purpose, we used Goto-Kakizaki rats, which develop type 2 diabetes with age. We found that female diabetic rats showed lower glycaemia levels with age than did diabetic males and that estrogens enhanced insulin sensitivity in diabetic females. Moreover, glucose uptake, measured by positron emission tomography, was higher in the female brain, cerebellum, and heart than in those from male diabetic rats. There were also sex-associated differences in the plasma metabolic profile as determined by metabolomics. The metabolic profile was similar between estrogen-replaced and control diabetic rats and different from ovariectomized diabetic rats. Oxidative stress is involved in these differences. We showed that hepatic mitochondria from females produced less hydrogen peroxide levels and exhibited lower xanthine oxidase activity. We also found that hepatic mitochondrial glutathione oxidation and lipid oxidation levels were lower in diabetic females when compared with diabetic males. Ovariectomy induced oxidative stress, and estrogen replacement therapy prevented it. These findings provide evidence for estrogen beneficial effects in type 2 diabetes and should be considered when prescribing estrogen replacement therapy to menopausal women.
Highlights
Diabetes mellitus is a chronic disease of high prevalence
We found that female diabetic rats showed lower glycaemia levels with age than did diabetic males and that estrogens enhanced insulin sensitivity in diabetic females
Given that there is a considerable difference in the prevalence of diabetes mellitus between men and women and that this is related to oxidative stress, our aim was to study the role of oxidative stress in the different prevalence of this disease between genders and to determine the possible protective role of estrogens, as well as the mechanisms by which this possible action exerts
Summary
According to the World Health Organization, there are currently approximately 143 million people with diabetes worldwide This figure is expected to rise to 300 million by the year 2025 due, above all, to the increase, aging, and urbanization of the population [1]. It is estimated that its prevalence is around 5%, increasing significantly in relation to age: it reaches figures between 10 and 15% in the population over 65 years of age and 20% if we consider only those older than 65 to 80 years [2] This happens because aging leads to an increase in fasting plasma glucose levels of 1 to 2 mg % per year and postprandial glycaemia increases from 8 to 20 mg %.
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