Chu CY, Kao YS,
Fong JC.Nigericin inhibits
insulin-stimulated glucose transport in 3T3-L1 adipocytes.
J Cell Biochem. 2002;85(1):83-91.
We used nigericin, a K+/H+
exchanger, to test whether glucose transport in 3T3-L1
adipocytes was modulated by changes in intracellular pH. Our
results showed that nigericin increased basal but decreased
insulin-stimulated glucose uptake in a time- and dose-dependent
manner. Whereas the basal translocation of GLUT1 was enhanced,
insulin-stimulated GLUT4 translocation was inhibited by
nigericin. On the other hand, the total amount of neither
transporter protein was altered. The finding that
insulin-stimulated phosphoinositide 3-kinase (PI 3-kinase)
activity was not affected by nigericin implies that nigericin
exerted its inhibition at a step downstream of PI 3-kinase
activation. At maximal dose, nigericin rapidly lowered cytosolic
pH to 6.7; however, this effect was transient and cytosolic pH
was back to normal in 20 min. Removal of nigericin from the
incubation medium after 20 min abolished its enhancing effect on
basal but had little influence on its inhibition of
insulin-stimulated glucose transport. Moreover, lowering
cytosolic pH to 6.7 with an exogenously added HCl solution had
no effect on glucose transport. Taken together, it appears that
nigericin may inhibit insulin-stimulated glucose transport
mainly by interfering with GLUT4 translocation, probably by a
mechanism not related to changes in cytosolic pH.
PMID: 11891852
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