Altered immunoreactivity of islet amyloid polypeptide (IAPP) may reflect major modifications of the IAPP molecule in amyloidogenesis.

Abstract:

:We have developed a mouse monoclonal antibody against rat/mouse islet amyloid polypeptide (IAPP). The antibody recognises an epitope in the N-terminal part of the molecule, which is conserved between different species. The antibody immunohistochemically labelled beta cells in normal islets of most different mammalian species including man and in one avian species. Previous immunohistochemical studies of human pancreatic tissue from individuals with non-insulin-dependent diabetes mellitus (NIDDM) have revealed a paradoxical and unexplained lack of IAPP immunoreactivity in beta cells close to amyloid in spite of the presence of IAPP mRNA. In contrast to these findings we show that the newly developed monoclonal IAPP antibody strongly labels such beta cells while islet amyloid deposits which are labelled by polyclonal antisera do not bind the monoclonal antibody. These findings with the polyclonal antisera and the monoclonal antibody indicate that IAPP undergoes one or several structural changes during the amyloidogenesis. Knowledge of these structural changes that may include abnormal folding or chemical modification of IAPP is probably important for the understanding of the amyloidogenesis and the pathogenesis of the islet lesion in NIDDM.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Ma Z,Westermark GT,Li ZC,Engström U,Westermark P

doi

10.1007/s001250050751

subject

Has Abstract

pub_date

1997-07-01 00:00:00

pages

793-801

issue

7

eissn

0012-186X

issn

1432-0428

journal_volume

40

pub_type

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