Oxidant stress reduces insulin responsiveness in 3t3-l1
adipocytes.
Rudich, Assaf, Nitzan Kozlovsky, Ruth Potashnik, and Nava Bashan.
Department of Clinical Biochemistry, Faculty of Health Sciences,
Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
APStracts 4:0007E, 1997.
Increased oxidant stress has been suggested to occur in diabetes, and
to contribute to the development of late diabetic complications.
Whether oxidant stress plays a role in the development or progression
of insulin resistance is not known. In this study we hypothesized
that exposing 3T3-L1 adipocytes to prolonged, micro molar
concentrations of H2O2 will reduce their acute metabolic responses to
insulin stimulation. 3T3-L1 adipocytes exposed to 25 mU/ml glucose
oxidase (GO) for 18 hours exhibited a 3-fold increase in basal 2
deoxyglucose uptake activity. However, net increase in 2DG uptake
activity following acute insulin (100 nM) stimulation was 355+/-56 in
control versus 198+/-41 pmole/mg prot.min. in GO pretreated cells,
P<0.05). Basal lipogenesis activity was significantly enhanced
by GO, but acute insulin stimulation resulted in significantly
reduced lipogenesis activity (29+/-4 Vs. 11+/-1 nmoles glucose/well
for control and 50 mU/ml GO, respectively, P=0.001). Glycogen
synthase a activity was reduced by GO (78+/-1 Vs. 43+/-2 pmoles
UDPG/mg prot.min., P=0.03), while insulin stimulation of glycogen
synthase was reduced, exhibiting a right shift in the insulin dose
response curve. These effects of GO were associated with increased
GLUT1 and reduced GLUT4 protein and mRNA content. In conclusion, our
data suggests that oxidant stress alters glucose transporters
expression and insulin-stimulated metabolism in 3T3-L1 adipocytes.
Received 20 August 1996; accepted in final form 20 December 1996.
APS Manuscript Number E407-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 21 January 1997