Ovarian hormone-induced beta-cell hypertrophy contributes to the homeostatic control of beta-cell mass in OLETF female rat, a model of Type II diabetes

Abstract

A sexual dimorphism regarding the incidence of diabetes mellitus in OLETF rat, a model of Type II diabetes, has been reported. As a result, the effects of ovarian hormones on beta cells per se was examined by comparing the capacity of beta-cell proliferation and changes in blood glucose and plasma insulin concentrations after a 70 % pancreatectomy. All female animals were randomly assigned to two protocols. The rats involved in protocol I received either a 70 % pancreatectomy (Px) or a sham pancreatectomy (sham) at 6 weeks of age, along with their diabetes-resistant counterparts, female LETO rats, which served as normal controls. The rats belonging to protocol II were given an ovariectomy (Ox) at 5 weeks of age, and one week later, they were subjected to either Px or the sham operation, with/without hormone (estradiol, 50 μg/kg; testosterone, 1 mg/kg) replacement. The findings indicate that the capacity for compensatory growth of beta cells after Px was affected by both sex hormonal and genetic components, since a 70 % Px resulted in sustained hyperglycaemia within the first week after surgery, but was ameliorated by an increase in beta-cell mass thereafter in the non-Ox Px OLETF rats. The Ox also caused a decline in beta-cell mass which could be improved by replacement with ovarian hormones. Not only endogenous but also replacement ovarian hormones, led to a beneficial effect on beta cells per se in OLETF female rats. This was reflected by an increased beta-cell mass accompanied by a parallel increase in plasma immunoreactive insulin concentration. The effects of ovarian hormones, however, contributed to the beta-cell hypertrophy rather than expansion of the beta-cell population to achieve glucose homeostasis, as evidenced by an increased area of individual beta-cell after Px rather than an increased BrdU-labelling index for the beta cells. The present study suggests that ovarian hormone-induced beta-cell hypertrophy may typically occur, to compensate for changes in functional demand as the results of a 70% Px in female OLETF rats.