REGULATION OF MUSCLE GLYCOGEN-METABOLISM BY CGRP AND AMYLIN - CGRP RECEPTORS NOT INVOLVED

The aim of the present study was to determine whether amylin and calci tonin gene-related peptide (CGRP) act through shared or distinct recep tors to inhibit insulin-stimulated incorporation of [C-14]-glucose int o glycogen. Rat amylin was 3 fold more potent than either rat alpha CG RP or rat beta CGRP at reducing glycogen synthesis from [C-14]-glucose in insulin-treated rat soleus muscle. This action was blocked by pept ide antagonists, with the rank order of potency being AC187>salmon cal citonin(8-32) (sCT(8-32)) > h-alpha CGRP(8-37) for antagonism of eithe r amylin or CGRP. The antagonist potency order correlated with affinit y for amylin receptors measured in rat nucleus accumbens but not CGRP receptors measured in rat L6 muscle cells. Inhibition of glucose incor poration into glycogen by amylin and CGRP appears to be mediated by sh ared receptors that have the pharmacological characteristics of amylin receptors, and are distinct from previously described CGRP receptors.