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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

Journal Article · · Experimental Cell Research; (United States)
; ; ;  [1];  [2]; ;  [3];  [4]
  1. Univ. of Uppsala (Sweden)
  2. Ludwig Inst. for Cancer Research, Uppsala (Sweden)
  3. Univ. Hospital Linkoeping (Sweden)
  4. Univ. of Minnesota, St. Paul (United States)

The authors 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 carboxyterminal 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, raccoon), but do not cross-react with IAPP from other tested species (mouse, rat, guinea pig, dog).

OSTI ID:
5714641
Journal Information:
Experimental Cell Research; (United States), Journal Name: Experimental Cell Research; (United States) Vol. 183:2; ISSN ECREA; ISSN 0014-4827
Country of Publication:
United States
Language:
English