Quantitative immunohistochemical analysis of islet amyloid polypeptide (IAPP) in normal, impaired glucose tolerant,...

Islet amyloid polypeptide (IAPP, "amylin") has been proposed as having important roles in the pathogenesis of type 2 diabetes mellitus via its biological activity and by forming islet amyloid. The domestic cat develops a type of diabetes that closely resembles type 2 diabetes in humans, including the frequent formation of islet amyloid deposits in the impaired glucose tolerant (IGT) and diabetic state. With the aid of computerized image analysis and immunohistochemistry, we examined the IAPP and insulin content in pancreatic islets of normal, IGT and diabetic cats. IAPP immunoreactivity in beta cells from IGT cats was significantly stronger (p < 0.01) as compared with cells from normal cats, while the insulin labelling strength was unchanged. Overtly diabetic cats were usually almost devoid of beta cells. As in humans, cellular IAPP but not IAPP in islet amyloid deposits was labelled by the newly developed monoclonal antibody to IAPP 4A5, thus providing further evidence that IAPP is modified by a yet unknown mechanism during the amyloidogenic process. The study provides evidence that an increased beta cell storage of IAPP independent of insulin may be an important factor in the early phase of the development of islet amyloid in this form of diabetes.