AJP - Renal Physiology, Vol 258, Issue 6 1625-F1633, Copyright © 1990 by American Physiological Society
Cadmium inhibits glucose uptake in primary cultures of mouse cortical tubule cells
S. S. Blumenthal, D. L. Lewand, M. A. Buday, J. G. Kleinman, S. K. Krezoski and D. H. Petering
Department of Medicine, Medical College of Wisconsin, Milwaukee.
We studied the effect of cadmium (Cd2+) on transport of
alpha-methylglucoside in primary cultures of mouse kidney cortical tubule
cells grown in defined medium. When cultured cells were exposed to Cd2+
concentrations from 0 to 6 microM for 24 h, uptake of alpha-methylglucoside
was inhibited in a dose-dependent manner by up to 50%. By contrast, acute
exposure of the cells to 7 microM Cd2+ for 60 min did not inhibit
alpha-methylglucoside uptake. Increasing Cd2+ concentrations progressively
decreased the Vmax of Na(+)-dependent glucose cotransport but not the Km
for glucose. Cell ATP/ADP ratios of unexposed monolayers and of cells
exposed to 4.5 microM Cd2+ for 24 h were 5.0 and 4.9, respectively (n = 3).
Intracellular volume, lactate dehydrogenase activity, and cell Na+ and K+
concentrations were unaltered even after 24 h of exposure to 7 microM Cd2+.
Untreated and Cd2+-treated monolayers preloaded with alpha-methylglucoside
released the sugar analogue into the medium at nearly identical rates,
indicating that Cd2+ did not alter cell permeability to glucose. Uptake of
the amino acid analogue alpha-(methylamino)isobutyric acid was not affected
by prior Cd2+ exposure. Whereas cell DNA content declined in Cd2(+)-exposed
plates, both Na(+)-glucose and Na(+)-amino acid cotransport were enhanced
at lower cell densities. Protein and DNA synthesis, estimated,
respectively, by incorporation of [3H]leucine and [3H]thymidine into
acid-insoluble material, were not significantly affected at 6 microM Cd2+.
We conclude that after a lag time Cd2+ selectively inhibits renal
Na(+)-dependent glucose transport despite an unchanged gradient for Na+
across the cell membrane.
