Amylin inhibits insulin-stimulated glucose uptake in C2C12 muscle cell line through a cholera-toxin-sensitive mechanism.

Rat amylin inhibits insulin-stimulated glucose uptake with an IC50 of 12.1 +/- 4.1 pM in C2C12 myotubes. The maximal inhibition is 64 +/- 5.4% observed at a 100-pM dose of the peptide. Consistently, presence of 100 pM amylin shifted the dose-response curve of insulin to the right, increasing the ED50 from 0.71 to 16 nM. No effect of amylin is observed on basal glucose uptake in these cells. Cholera-toxin treatment of the cells did not affect the insulin-stimulated glucose uptake, while the inhibitory effect is completely lost in toxin-treated cells. These findings strongly suggest that rat amylin is active at a physiological concentration and the amylin inhibition of glucose uptake is mediated through a cholera-toxin-sensitive mechanism.