ISLET AMYLOID IN TYPE-2 (NON-INSULIN-DEPENDENT) DIABETES

Amyloid deposits are found in pancreatic islets of 90% of type 2 (non- insulin-dependent) diabetic subjects at postmortem. Islet amyloid is f ormed from islet amyloid polypeptide (IAPP). IAPP is a 37 amino acid p eptide which is a normal constituent of beta cells and is co-secreted with insulin in animals and in man. The causative factors for fibrillo genesis of IAPP are unclear, but could be related to the sequence of I APP and abnormal production of the peptide. The lack of islet amyloid in rodent models of diabetes is due to proline substitutions in the am yloidogenic region of IAPP. Amyloid fibrils are deposited between beta cells and islet capillaries: fibrils in invaginations of the plasma m embrane may interfere with membrane signalling and insulin release. Am yloid fibrils are formed within 2 days in culture in islets isolated f rom transgenic mice expressing the gene for human IAPP, but not in viv o. Overexpression and decreased clearance of human IAPP from islet spa ces may be important factors. Progressive deposition of IAPP fibrils c ombined with the associated reduction in the insulin-secreting beta ce lls is likely to contribute to deterioration of islet function in the course of type 2 diabetes.