Amylin

Amylin (IAPP) is a 37-amino acid peptide hormone co-secreted with insulin from pancreatic beta cells in approximately a 100:1 ratio (insulin:amylin). It plays a critical role in postprandial glycemic control by slowing gastric emptying, suppressing glucagon, and promoting satiety. Amylin is the structural template for pramlintide (Symlin, FDA-approved) and the next-generation analog cagrilintide.

Amylin activates amylin receptors (AMY1–3), which are heterodimers of calcitonin receptors (CTR) and receptor activity-modifying proteins (RAMPs 1–3). In the area postrema and nucleus accumbens, amylin signaling reduces food intake and slows gastric motility. It suppresses postprandial glucagon secretion in a glucose-dependent manner. Pathological aggregation of IAPP into amyloid fibrils in beta cell islets is implicated in type 2 diabetes progression via inflammasome activation, ER stress, and membrane disruption.

Pramlintide (synthetic amylin analog) is FDA-approved as an adjunct to insulin in T1D and T2D, reducing postprandial glucose excursions by ~40 mg/dL and body weight by 1–2 kg. Cagrilintide (Novo Nordisk long-acting amylin analog) combined with semaglutide (CagriSema) produced ~25% weight loss in Phase 2 trials (SCALE) and is advancing to Phase 3. IAPP amyloid research is central to understanding beta cell failure in T2D.

Peptides commonly paired with Amylin for synergistic effects.