Effects of Ovariectomy on Insulin Resistance and β - Cell Function and Mass

The prevalence of type-2 diabetes increases remarkably in post-menopausal women, possibly because insulin secretion fails to compensate for the insulin resistance induced in various tissues by estrogen insufficiency. However, this has not been fully defined. Therefore, the present study investigated whether an ovariectomy (OVX) would increase insulin resistance and decrease the β-cell function and mass in female rats with and without a 90% pancreatectomy (Px). Female rats aged 15 weeks were divided into four groups: 1) OVX＋Px, 2) SOVX (sham operation of OVX)＋Px, 3) OVX＋SPx (sham operation of Px), and 4) SOVX＋ SPx, and given a 30% fat diet for 8 weeks. At the end of the experimental period, the islet function and insulin resistance were determined using a hyperglycemic clamp and a euglycemic hyperinsulinemic clamp, respectively. The OVX only increased the body weight in the SPx rats, which was partially related to the food intake. Yet, the OVX did increase the peripheral insulin resistance, while the Px increased this resistance further. The OVX and Px both exacerbated the islet function, as measured by the insulin secretion pattern, while delaying and decreasing the first-phase insulin secretion. The OVX only decreased the proliferation of β-cells in the Px rats, while increasing apoptosis in both the Px and SPx rats. As a result, the OVX decreased the β-cell mass in the Px rats, but increased the mass in the SPx rats. In conclusion, an OVX was found to accelerate the development and progression of diabetes by increasing the insulin resistance and decreasing the β-cell mass. Therefore, menopause can be a risk factor for type-2 diabetes, mainly due to a deceased proliferation of β-cells.