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Influence of castration-induced testosterone and estradiol deficiency on obesity and glucose metabolism in male Göttingen minipigs |
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| Authors: | Berit Oestergaard Christoffersen Laust Peter Gade Ove Svendsen Kirsten Raun |
| Affiliation: | a Veterinary Pathobiology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark b Diabetes and Obesity Pharmacology, Novo Nordisk A/S, Maaloev, Denmark c Animal Unit, Novo Nordisk A/S, Ganloese, Denmark |
| Abstract: | Low testosterone and estradiol concentrations are predictive for the development of the metabolic syndrome in men and women, respectively. The aim of this study was to investigate the influence of sex hormone deficiency on food intake, body weight, body composition and glucose metabolism in male Göttingen minipigs.Five adult male Göttingen minipigs were studied before castration (pre-cast), 10-18 days (post-cast 1) and 10-11 weeks (post-cast 2) after castration. Parameters of interest were food intake, body weight, body fat percentage and sex hormone concentrations. Furthermore glucose tolerance, glucagon suppression, insulin resistance, beta cell function and disposition index were evaluated by oral and intravenous glucose tolerance tests.Castration led to almost complete disappearance of circulating testosterone and estradiol and secondarily to increased food intake, body weight and body fat percentage. Ten-eighteen days sex hormone deficiency (post-cast 1) did not significantly change any of the investigated metabolic parameters compared to pre-cast levels. Ten weeks after castration (post-cast 2) significant insulin resistance, glucose intolerance and hyperglucagonemia was found, and the beta cell function and the disposition index both were decreased.In conclusion, castration-induced sex hormone deficiency in male Göttingen minipigs results in hyperphagia, obesity and disturbed glucose metabolism, which are some of the features typical for the human metabolic syndrome. |
| Keywords: | AIRG, acute insulin response to glucose calculated from an intravenous glucose tolerance test ANOVA, analysis of variance AUC, area under the curve BCF, beta cell function BW, body weight CV, coefficient of variation DEXA, dual energy X-ray absorptiometry DI, disposition index EDTA, ethylenedinitrilotetraacetic acid ISIcomp, insulin sensitivity index calculated from an oral glucose tolerance test (Matsuda index) IVGTT, intravenous glucose tolerance test KG, intravenous glucose tolerance index OGTT, oral glucose tolerance test PRE-CAST, the period before castration POST-CAST 1, the period from 0 to 18 days after castration POST-CAST 2, the period from 18 days to 11 weeks after castration S2, insulin sensitivity index calculated from an intravenous glucose tolerance test SDS, special Diets Services SEM, standard error of mean Vd, distribution volume |
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