8-37h-CGRP antagonizes actions of amylin on carbohydrate metabolism in vitro and in vivo

Abstract

8-37hCGRP is a potent antagonist at calcitonin gene-related peptide (CGRP) liver membrane receptors; it also blocks vasodilator actions of CGRP and the related peptide, amylin, in intact rats. We now report that 8-37hCGRP antagonizes amylin inhibition of insulin-stimulated labelled glucose uptake into isolated rat soleus muscle, and inhibits amylin-evoked elevation of plasma lactate and glucose in fasted anaesthetized rats. The different relative potencies of the 3 ligands (amylin, CGRP, 8-37hCGRP) on the liver receptor and on the soleus muscle point to distinct CGRP receptors in liver membranes and amylin receptors on muscle cells.