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.
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 microg/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.
Zhu
M
M
Department of Laboratory Medicine, School of Medicine, University of Tokushima, Tokushima-City, Japan.
Mizuno
A
A
Kuwajima
M
M
Ogino
T
T
Murakami
T
T
Noma
Y
Y
Sano
T
T
Shima
K
K
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000473:pathology* / Q000503:physiopathology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006984:Hypertrophy; D007113:Immunity, Innate; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology / Q000503:physiopathology*; D010180:Pancreatectomy; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D013739:Testosterone / Q000031:analogs & derivatives / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D013739:Testosterone; D004958:Estradiol; C004648:testosterone enanthate