The physiology of calcitonin gene-related peptide in the islet compared with that of islet amyloid polypeptide (amylin).

Following the discovery of a second gene containing a CGRP-like sequence, we demonstrated that "beta-CGRP" was indeed translated as a 37-amino acid peptide in vivo and was the predominant form of CGRP produced by the enteric nervous system. The presence of CGRP in the islet has been reported by several groups. We now show that beta-CGRP is again the major form. Another 37-amino acid peptide was recently isolated from islet amyloid deposits and found to have approximately 50% amino acid sequence homology with CGRP. Islet amyloid polypeptide, or amylin, is co-localized with insulin to the beta-cell secretory granule and is synthesized and released in parallel with insulin in response to a range of physiological and pharmacological stimuli. IAPP was subsequently shown, like CGRP, to inhibit the release of insulin pharmacologically. Interestingly, it was also shown to decrease the uptake of glucose by striated muscle, though it was considerably less potent than CGRP. This led to the suggestion that IAPP might be a circulating hormone regulating peripheral insulin sensitivity. Infusion of IAPP in human volunteers to produce plasma concentrations more than 100-fold higher than those seen physiologically, however, failed to alter peripheral glucose disposal. We conclude that beta-CGRP and IAPP are likely to play a role in local paracrine control of the islet.