K. Handoko et al., Insulin attenuates the stimulatory effects of tumor necrosis factor alpha on 11 beta-hydroxysteroid dehydrogenase 1 in human adipose stromal cells, J STEROID B, 72(3-4), 2000, pp. 163-168
Citations number
25
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Obesity is frequently associated with insulin-resistance and abnormal gluco
se homeostasis. Recent evidence indicates that TNF alpha may play a role in
mediating the insulin-resistance of obesity through its overexpression in
adipose tissue. Previously, we have shown that human adipose stromal cells
contain 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) mRNA and
activity. The present study was designed to examine the effects of insulin
on 11 beta-HSD1 expression in human adipose stromal cells under basal and
TNF alpha-stimulated conditions. The cells were obtained from breast adipos
e tissue by collagenase digestion, and grown to confluence under replicatin
g conditions in 10% fetal bovine serum. The cells were transferred to serum
-free medium for 24 h prior to treatment with either TNF alpha, insulin or
both for a further 24 h. The level of 11 beta-HSD1 reductase activity was d
etermined by measuring the conversion of [H-3]-cortisone to [H-3]-cortisol
at a substrate concentration of 10 nM, Treatment with TNF alpha at concentr
ations of 0.1-10 ng/ml resulted in a dose dependent increase in 11 beta-HSD
1 reductase activity from 1.5 to 10-fold. Insulin (0.1-100 nM) had no effec
t under basal conditions, but inhibited the stimulatory effects of TNF alph
a (5 ng/ml) on 11 beta-HSD1 reductase activity in a dose dependent fashion
(8-66%) inhibition. Northern blot analysis revealed corresponding changes i
n the level of 11 beta-HSD1 mRNA, suggesting that the effects of TNF alpha
and insulin on 11 beta-HSD1 activity are mediated at the level of gene tran
scription. The interaction between insulin and TNF alpha suggests that loca
l and systemic factors may act in a concerted fashion to modulate glucocort
icoid activity in adipose and other peripheral tissues. (C) 2000 Elsevier S
cience Ltd. All rights reserved.