Effect of (8-32) salmon calcitonin, an amylin antagonist, on insulin, glucagon and somatostatin release: study in the perfused pancreas of the rat.

1. The 8-32 fragment of salmon calcitonin ((8-32) sCT) has been proposed as a highly selective amylin receptor antagonist. 2. In the present study, we have studied the influence of (8-32) sCT on the inhibitory effect of both amylin and its structural congener, calcitonin gene-related peptide (CGRP), on insulin secretion in the rat perfused pancreas. 3. Both amylin and CGRP, at 75 pM, clearly inhibited glucose-induced insulin release (by 80% and by 70%, respectively). Simultaneous infusion of 10 microM (8-32) sCT reversed the inhibitory effect of amylin (by 80%; P < 0.05 vs. amylin experiments) but did not significantly affect the inhibition of glucose-induced insulin output elicited by CGRP. Furthermore, at the same concentration (10 microM), (8-32) sCT alone potentiated the insulin response to 7 mM glucose (2.5 fold; P < 0.05) whilst it did not affect glucagon or somatostatin secretion. 4. The observation that infusion of an amylin antagonist into the rat pancreas potentiates the insulin response to glucose, favours the concept of endogenous amylin as an inhibitor of insulin release. 5. Finally, as an amylin antagonist at the level of the beta-cell, (8-32) sCT might be considered of potential interest in experimental and clinical pharmacology.