Amyloid in human islets of langerhans: Immunologic evidence that islet amyloid polypeptide is modified in amyloidogenesis

Amyloid derived from the beta-cell product islet amyloid polypeptide (IAPP) has been implicated for a beta-cell lesion in Type II diabetes mellitus. T he pathogenesis of islet amyloid is poorly understood, and in addition to a n amyloidogenic IAPP molecule and possibly increased concentration of IAPP, other unknown factors seem to be included. It was shown previously that po lyclonal rabbit LAPP antisera label beta cells close to amyloid only weakly . Whether this lack of immunoreactivity depends on lack of IAPP or on hidde n epitopes is in question. In the present study, we show that the IAPP immu noreactivity of these beta cells is possible to retrieve. On the other hand , the monoclonal IAPP antibody 4A5, which labels IAPP in beta cells, does n ot label IAPP in its native amyloid form. We show evidence that this lack o f immunoreactivity is not dependent on conformational change of the IAPP mo lecules in the amyloidogenesis but is likely owing to glycation of IAPP in human islet amyloid deposits.