Regulation of glucose transport and glut1 expression by iron
chelators in muscle cells in culture.
Potashnik, Ruth, Nizan Kozlovsky, Smadar Ben-Ezra, Assaf Rudich, and
Nava Bashan.
Clinical Biochemistry Unit. Faculty of Health Sciences, Ben-Gurion
University of the Negev, Beer-Sheva, Israel
APStracts 2:0150E, 1995.
Possible association between the degree of iron load and glucose
metabolism has been postulated by both in-vivo and in-vitro studies.
As skeletal muscle plays a major role in whole body glucose
utilization, we evaluated the effect of iron chelators deferoxamine
(DFO) and bipyridyl (Bip) on glucose metabolism and transport in
cultured L6 muscle cells. Bip (0.1 mM) or DFO (0.5 mM) added for 24
hours to the culture medium increased glucose consumption, lactate
production and 14C-glucose incorporation into glycogen, by
approximately 2-fold. 2-Deoxyglucose uptake by L6 myotubes increased
time-dependently, reaching a 5-fold and 2.5-fold increase after 12
hours, for Bip and DFO, respectively. Insulin induced a 2.5-fold
increase in glucose uptake in untreated cells, which was additive to
the chelators' effect. Iron chelators' induced glucose transport
stimulation was inhibited by cycloheximide (2.5 [mu]g/ml), indicating
dependence on de-novo protein synthesis. Increase in GLUT1 protein
and mRNA concentration, without changes in GLUT4, were found to be
responsible for iron chelators' effects. We conclude, that L6 cells
adapt to reduction in iron availability by increasing glucose
utilization through an enhanced expression of GLUT1, without loosing
their physiologic response to insulin.
Received 1 May 1995; accepted in final form 11 July 1995.
APS Manuscript Number E194-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.