Amylin Compared with Calcitonin Gene-Related Peptide: Structure, Biology, and Relevance to Metabolic Disease

ISLETβ-cells play a central role in the regulation of most cells in the body through secretion of insulin. These cells are now known to secrete a second hormone-like protein, amylin, also known as islet or insulinoma amyloid polypeptide (IAPP) (1–4) as well as numerous other compounds (5) in response to stimuli that elicit insulin release (6–9). Amylin is structurally similar to calcitonin gene-related peptide (CGRP) (1, 2), a widely distributed neuropeptide (10) and potent vasodilator (11–13). It is the major protein in islet amyloid (1, 3), extracellular accumulation of which occurs in most patients with non-insulin-dependent diabetes mellitus (NIDDM) (14) and increases in extent with duration in this disease (15).

Amylin and CGRP produce similar biological effects in many tissues. Their actions in skeletal muscle and liver stimulate glycogen breakdown and oppose the actions of insulin (16–22), perhaps through evoked alterations in the activity of enzymes including glycogen phosphorylase (23–25) and glycogen synthase (23, 25).