Pancreatic Islet Amyloid and Diabetes

Deposition of amyloid in pancreatic islets is a feature of type 2 diabetes in man but the causal factors are unknown. Progressive amyloidosis results in loss of insulin-producing cells and increased severity of disease. The fibril component is a 37-amino-acid peptide, islet amyloid polypeptide (IAPP; amylin), which is a normal cellular peptide, cosecreted with insulin; the species-specific amino-acid sequence of IAPP is unaltered in diabetes. Peptide refolding in islet perivascular spaces to form β-sheets could be related to production of fragments of the precursor peptide, proIAPP. Islet amyloidosis is not a causal factor for hyperglycemia in man but contributes to onset of diabetes in non-human primates and transgenic rodent models. Because islet amyloidosis cannot be detected in vivo, clinical development of inhibitors is likely to be difficult.