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Characterization of metformin transport system in NIH 3T3 cells
Author(s) -
Khan Naim A.,
Wiernsperger Nicolas,
Quemener Veronique,
Havouis René,
Moulinoux Jacques P.
Publication year - 1992
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041520212
Subject(s) - metformin , spermidine , ionophore , chemistry , membrane transport , ornithine , polyamine , biochemistry , medicine , arginine , endocrinology , biology , insulin , membrane , amino acid , enzyme
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.