Islet amyloid polypeptide (IAPP): cDNA cloning and identification of an amyloidogenic region associated with the species-specific occurrence of age-related diabetes mellitus
- Univ. of Uppsala (Sweden)
- Ludwig Inst. for Cancer Research, Uppsala (Sweden)
- Univ. Hospital Linkoeping (Sweden)
- 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), Vol. 183:2; ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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DIABETES MELLITUS
PATHOGENESIS
POLYPEPTIDES
AMINO ACID SEQUENCE
RECOMBINANT DNA
DNA SEQUENCING
AMYLASE
BIOLOGICAL EVOLUTION
CATS
DOGS
GUINEA PIGS
MAN
PANCREAS
PHOSPHORUS 32
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
DNA
ENDOCRINE DISEASES
ENDOCRINE GLANDS
ENZYMES
GLANDS
GLYCOSYL HYDROLASES
HYDROLASES
ISOTOPES
LIGHT NUCLEI
MAMMALS
METABOLIC DISEASES
MOLECULAR STRUCTURE
NUCLEI
NUCLEIC ACIDS
O-GLYCOSYL HYDROLASES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
PHOSPHORUS ISOTOPES
PRIMATES
PROTEINS
RADIOISOTOPES
RODENTS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES
550301* - Cytology- Tracer Techniques