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INSULIN-GLUCAGON-GI PEPTIDES-DIABETES MELLITUS |
Department of Medicine III, Division of Endocrinology & Metabolism, University of Vienna, A-1090 Vienna, Austria
Address all correspondence and requests for reprints to: Clemens Fürnsinn, Ph.D., University of Vienna, Department of Medicine III, Division of Endocrinology and Metabolism, Wahringer Gurtel 18-20, Vienna A-1090, Austria.
Insulin sensitizing thiazolidinediones (TZDs) inhibit steroidogenic
enzyme activities in vitro and affect plasma steroids
in women with polycystic ovary syndrome. This study was to examine TZD
action on circulating steroids in male genetically obese Zucker rats
(fa/fa), which were treated with troglitazone or rosiglitazone (0.3%
and 0.01% food admixture, respectively) and were compared to untreated
obese and lean littermates. After 36 days of TZD administration,
obesity- associated derangement of carbohydrate metabolism was
ameliorated (e.g., insulin-stimulated glucose oxidation by isolated
soleus muscle, nmol/g/h: lean controls, 1049 ± 100; obese controls,
518 ± 30; troglitazone-treated obese, 672 ± 43; rosiglitazone-treated
obese, 761 ± 77; p < 0.01 each vs. obese controls). While
plasma pregnenolone and testosterone were neither affected by obesity
nor by TZDs, a marked reduction of 17-hydroxyprogesterone in obese
vs. lean controls (27 ± 3 vs. 58 ± 10
ng/dl; p < 0.01) was partially reversed by TZD treatment (46 ± 5
and 48 ± 9 ng/dl for troglitazone and rosiglitazone, respectively; p
< 0.02 each vs. untreated obese). Plasma
5-
-dihydrotestosterone, in contrast, was not reduced by obesity (76
± 9 vs. 59 ± 7 ng/dl in obese vs. lean
controls; n.s.) but blunted by TZD treatment of obese rats (38 ± 4 and
44 ± 3 ng/dl for troglitazone and rosiglitazone, respectively; p <
0.05 each vs. untreated obese). We conclude that (i) oral
TZD treatment influences circulating steroid concentrations of male
obese Zucker rats, and (ii) these effects are at least in part mediated
via mechanisms other than those underlying TZD-induced insulin
sensitization.
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