Effects of sex hormones on the development of diabetes and pancreatic islet gene expression in obese type 2 diabetes model ZFDM rat.

Abstract

Sex differences have been observed in the onset of type 2 diabetes, with men being more likely to develop the disease than women. There is a clear sex difference in the development of diabetes in obese type 2 diabetes model ZFDM rats, with all males developing diabetes, but none of the females. In the present study, we examined the effects of sex hormones on the development of diabetes and gene expression in the pancreatic islets of ZFDM rats. All experiments were performed using 6-week-old ZFDM rats homozygous for the leptin receptor mutation (fatty, fa). Orchiectomy did not affect the development of diabetes but slightly suppressed non-fasting blood glucose levels in male ZFDM rats. Except for one diabetic rat, ovariectomy did not affect non-fasting blood glucose levels but impaired glucose tolerance in female ZFDM rats, which was accompanied by accelerated islet fibrosis and pancreatic β-cell loss. Administration of the female hormone (17β-estradiol, E2) did suppress the development of diabetes in male ZFDM rats. Pair feeding matched with the E2-administered group also suppressed the development of diabetes in male ZFDM rats. Direct E2 treatment of the pancreatic islets of diabetic male ZFDM rats changed the expression of genes related to type 2 diabetes and insulin secretion closer to those of obese non-diabetic male ZF rats. These results suggest that female hormones have the suppressive effects on the development of diabetes, whereas male hormones, if any, have the opposite effects in ZFDM rats.