Castration causes insulin but not leucine resistance in male rats
Open Access
- Author:
- Jiao, Qianning
- Graduate Program:
- Physiology
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- None
- Committee Members:
- Charles H Lang, Thesis Advisor/Co-Advisor
Charles H Lang, Thesis Advisor/Co-Advisor - Keywords:
- insulin resistance
castration
testosterone
leucine resistance - Abstract:
- Testosterone has long been reported to have anabolic effects. Low concentrations of plasma testosterone have been associated with insulin resistance, which is an important upstream driver for metabolic abnormalities such as hyperglycemia, hypertension, or hyperlipidemia, and increased cardiovascular risk. The purpose of this thesis is to test the hypothesis that lack of testosterone also impairs the anabolic response to amino acids, specifically leucine (Leu), which stimulates protein synthesis through mammalian target of rapamycin (mTOR) pathway. 6- week old castrated rats were measured body composition in a 9-week period, during which a glucose tolerance test was performed to confirm that low testosterone leads to insulin resistance. Compared to control rats, a decrease in both body weight and lean body mass was observed in castrated animals. After that, Leu or saline (Sal) was administered to castrated and time-matched control rats. The gastrocnemius and liver were removed 20 min later for assessment of protein synthesis and signaling components important in peptide-chain initiation. No change in the ability of leucine to induce phosphorylation of eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1) was observed. Both protein synthesis and degradation rate did not change significantly in castrated rats. The decrease in lean body mass cannot be attributed to changes in protein degradation rate, and it is possible that low mTOR activity and protein synthesis rate induced by castration is responsible for the erosion of muscle mass. Castration does not change the effect of leucine to induce 4E-BP1 and S6K1 phosphorylation, hence, castration may influence anabolic physiological processes by influencing upstream signals of mTOR, which are independent of the insulin signaling pathway.