Cadmium inhibits glucose uptake in primary cultures of mouse cortical tubule cells.
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.
Blumenthal
S S
SS
Department of Medicine, Medical College of Wisconsin, Milwaukee.
Lewand
D L
DL
Buday
M A
MA
Kleinman
J G
JG
Krezoski
S K
SK
Petering
D H
DH
D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport; D002104:Cadmium / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics; D007672:Kidney Cortex; D007684:Kidney Tubules / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008757:Methylglucosides / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014867:Water / Q000378:metabolism
D000621:Aminoisobutyric Acids; D008757:Methylglucosides; D002104:Cadmium; D014867:Water; C017911:2-(methylamino)isobutyric acid; C027020:methylglucoside; D012964:Sodium; D007770:L-Lactate Dehydrogenase; D005947:Glucose; D011188:Potassium