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. The pathogenesis of islet amyloid is poorly understood, and in addition to an amyloidogenic IAPP molecule and possibly increased concentration of IAPP, other unknown factors seem to be included. It was shown previously that polyclonal rabbit IAPP antisera label beta cells close to amyloid only weakly. Whether this lack of immunoreactivity depends on lack of IAPP or on hidden epitopes is in question. In the present study, we show that the IAPP immunoreactivity of these beta cells is possible to retrieve. On the other hand, the monoclonal IAPP antibody 4A5, which labels IAPP in beta cells, does not label IAPP in its native amyloid form. We show evidence that this lack of immunoreactivity is not dependent on conformational change of the IAPP molecules in the amyloidogenesis but is likely owing to glycation of IAPP in human islet amyloid deposits.
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Division of Molecular and Immunological Pathology, Linköping University, Sweden.
Westermark
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Westermark
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D000682:Amyloid / Q000032:analysis* / Q000737:chemistry; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D006031:Glycosylation; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000737:chemistry* / Q000648:ultrastructure*; D008854:Microscopy, Electron
D000682:Amyloid; D000911:Antibodies, Monoclonal; D058228:Islet Amyloid Polypeptide