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.
Sheriff
S
S
Department of Surgery, University of Cincinnati Medical Center, Ohio 45267.
Fischer
J E
JE
Balasubramaniam
A
A
D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007328:Insulin / Q000502:physiology*; D058228:Islet Amyloid Polypeptide; D051379:Mice; D008954:Models, Biological; D009132:Muscles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D002772:Cholera Toxin; D005947:Glucose