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Characterization of metformin transport system in NIH 3T3 cells

✍ Scribed by Naim A. Khan; Nicolas Wiernsperger; Veronique Quemener; René Havouis; Jacques P. Moulinoux

Publisher
John Wiley and Sons
Year
1992
Tongue
English
Weight
686 KB
Volume
152
Category
Article
ISSN
0021-9541

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

The biochemical properties of the metformin transport system were studied in NIH 3T3 cells. ^14^C‐metformin uptake appeared to be a sodium dependent process. Iso‐osmotical replacement of Na^+^ by choline chloride in the assay medium resulted in a decrease of metformin uptake. Amiloride (200 μM) inhibited the metformin transport by 35% in these cells. Gramicidin, a channel ionophore, was the most effective in inhibiting the metformin transport as compared to valinomycin, a mobile ion carrier, and Ca^2+^ ionophore (A 23187). Loading of cells with asparagine, ornithine, or polylysine did not influence the uptake process. However, the addition of lysine or arginine significantly stimulated the metformin uptake by NIH 3T3 cells. Similarly, the addition of metformin stimulated the arginine uptake by these cells, suggesting that metformin shares the y^+^ transport system. Metformin inhibited competitively the uptake of ^14^C‐spermidine, a molecule of the polyamine family, by NIH 3T3 cells, whereas the latter failed to influence the uptake of the former significantly by these cells. Incubation of NIH 3T3 cells in the presence of difluoromethyl‐ornithine (a suicidal inhibitor of polyamine biosynthesis) stimulated the spermidine, but not the metformin, uptake by these cells. Interestingly, a prolonged incubation of these cells in the presence of metformin failed to down‐regulate the spermidine transport process. The spermidine‐ and methylglyoxal‐bis(guanylhydrazone), MGBG‐transport deficient (3T3^MG^) cells which do not accumulate exogeneous spermidine or MGBG, took up ^14^C‐metformin. However, ^14^C‐metformin uptake by 3T3^MG^ cells was lower than that by normal NIH 3T3 cells. © 1992 Wiley‐Liss, Inc.

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