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Islet
amyloid polypeptide (IAPP):cDNA cloning and identification of an
amyloidogenic region associated with the species-specific occurrence of
age-related diabetes mellitus
C Betsholtz, V Svensson, F Rorsman, U Engström, G T Westermark, E
Wilander, K Johnson, P Westermark
Abstract
broadcast on www.provet.co.uk
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Abstract
We have cloned and sequenced a human islet amyloid polypeptide (IAPP) cDNA. A
secretory 89 amino acid IAPP protein precursor is predicted from which the 37
amino acid IAPP molecule is formed by amino- and carboxyterminal proteolytic
processing. The IAPP peptide is 43-46% identical in amino acid sequence to the
two members of the calcitonin gene-related peptide (CGRP) family. Evolutionary
conserved proteolytic processing sites indicate that similar proteases are
involved in the maturation of IAPP and CGRP and that the IAPP amyloid
polypeptide is identical to the normal proteolytic product of the IAPP
precursor. A synthetic peptide corresponding to a carboxyteminal fragment of
human IAPP is shown to spontaneously form amyloid-like fibrils in vitro.
Antibodies against this peptide cross-react with IAPP from species that
develop amyloid in pancreatic islets in conjunction with age-related diabetes
mellitus (human, cat, racoon), but do not cross-react with IAPP from other
tested species (mouse, rat, guinea pig, dog). Thus, a species-specific
structural motif in the putative amyloidogenic region of IAPP is associated
with both amyloid formation and the development of age-related diabetes
mellitus. This provides a new molecular clue to the pathogenesis of this
disease.
Reference
EXPERIMENTAL CELL RESEARCH , 183(2):484-493
1989 Updated January 2016
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