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

Islet amyloid polypeptide (IAPP, "amylin") has been proposed as having impo rtant roles in the pathogenesis of type 2 diabetes mellitus via its biologi cal activity and by forming islet amyloid. The domestic cat develops a type of diabetes that closely resembles type 2 diabetes in humans, including th e frequent formation of islet amyloid deposits in the impaired glucose tole rant (IGT) and diabetic state. With the aid of computerized image analysis and immunohistochemistry, we examined the IAPP and insulin content in pancr eatic islets of normal, IGT and diabetic cats, IAPP immunoreactivity in bet a cells from IGT cats was significantly stronger (p < 0.01) as compared wit h cells from normal cats, while the insulin labelling strength was unchange d. Overtly diabetic cats were usually almost devoid of beta cells. As in hu mans, 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 amylo idogenic process. The study provides evidence that an increased beta cell s torage of IAPP independent of insulin may be an important factor in the ear ly phase of the development of islet amyloid in this form of diabetes.