Effects of castration on insulin levels and glucose tolerance in the mouse differ from those in man

Abstract

Plasma insulin concentration is increased in prostate cancer patients during androgen deprivation therapy (ADT) and hyperinsulinemia has been associated with aggressive prostate cancer behavior. To investigate the possible role of castration-induced hyperinsulinemia as a mechanism that may attenuate the beneficial effects of ADT in patients with prostate cancer, a murine model would be useful. We therefore investigated long-term metabolic effects of castration in several mouse models. We studied the long-term influence of castration on energy intake, body weight, glucose tolerance, plasma-insulin, plasma insulin-like growth factor-1 (IGF-1), plasma adiponectin, and plasma leptin in C57BL/6, Swiss nu/nu, and CB17 scid mice receiving various diets. In each case, mice were randomized to have either bilateral orchiectomy or a sham operation. Energy intake, body weight, blood glucose levels in glucose tolerance test, plasma insulin, plasma IGF-1, and plasma leptin level in all had a trend to be decreased in castrated as compared to sham operated mice. Plasma adiponectin level was increased in the castrated mice. The effects of castration on glucose, insulin, and related markers in several mouse models studied does not coincide with clinical observations; further studies in this area will require clinical research and/or the use of alternate models such as the dog.