Islet Amyloid Polypeptide IAPP, Amylin

ISLET AMYLOID POLYPEPTIDE IAPP, AMYLIN

Amylin is a 37-amino-acid peptide originally derived from islet amyloid deposits in pancreas material from patients with long-standing type 2 diabetes or insulinomas. It is produced by pancre-atic beta cells, packaged within beta-cell granules in a concentration 1–2% that of insulin and co-secreted with insulin in a pulsatile manner and in response to physiologic secretory stimuli. Approximately 1 molecule of amylin is released for every 10 molecules of insulin. It circulates in a glycated (active) and nonglycated (inactive) form with physiologic concentrations rang-ing from 4 to 25 pmol/L and is primarily excreted by the kidney. Amylin appears to be a member of the superfamily of neuroregula-tory peptides, with 46% homology with the calcitonin gene-re-lated peptide CGRP . The physiologic effect of amylin may be to modulate insulin release by acting as a negative feedback on insulin secretion. At pharmacologic doses, amylin reduces glucagon secretion, slows gastric emptying by a vagally medicated mechanism, and centrally decreases appetite. An analog of amylin, pramlintide (see previous section), differs from amylin by the substitution of proline at positions 25, 28, and 29. These modifications make pramlintide soluble and non–self-aggregating, and suitable for pharmacologic use.