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Updated: Jun 12, 2026
Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
Effects of castration on insulin levels and glucose tolerance in the mouse differ from those in man
Takamitsu Inoue1, Mahvash Zakikhani, Stéphanie David
1Lady Davis Institute for Medical Research of the Jewish General Hospital, Montreal, Quebec, Canada.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Castration decreased insulin and body weight in mice, contrary to clinical observations in prostate cancer patients undergoing androgen deprivation therapy (ADT). Further research is needed to understand these metabolic effects.
Area of Science:
- Endocrinology
- Oncology
- Metabolic Research
Background:
- Hyperinsulinemia is observed in prostate cancer patients during androgen deprivation therapy (ADT).
- Hyperinsulinemia may counteract the therapeutic benefits of ADT in prostate cancer.
- Investigating castration's metabolic effects in mouse models is crucial to understand this phenomenon.
Purpose of the Study:
- To investigate the long-term metabolic consequences of castration in mice.
- To determine if castration influences energy intake, body weight, glucose metabolism, and key hormonal markers.
- To assess the potential of mouse models for studying ADT-related metabolic changes in prostate cancer.
Main Methods:
- Long-term study of castration effects in C57BL/6, Swiss nu/nu, and CB17 scid mice.
- Evaluation of energy intake, body weight, glucose tolerance, plasma insulin, IGF-1, adiponectin, and leptin.
- Comparison between bilaterally orchiectomized (castrated) mice and sham-operated controls.
Main Results:
- Castrated mice showed a trend towards decreased energy intake, body weight, blood glucose, plasma insulin, and plasma leptin.
- Plasma adiponectin levels were elevated in castrated mice compared to controls.
- These metabolic changes in mice did not align with clinical observations in prostate cancer patients.
Conclusions:
- The metabolic effects of castration observed in the studied mouse models do not mirror clinical findings in prostate cancer patients on ADT.
- Further investigation is warranted, potentially utilizing clinical research or alternative animal models like dogs.
- The current mouse models may not fully recapitulate the complex interplay between castration, insulin, and prostate cancer progression observed in humans.
