Sequence divergence in a specific region of islet amyloid polypeptide (IAPP) explains differences in islet amyloid formation between species.
Amyloid deposits in the islets of Langerhans occur in association with type 2 diabetes mellitus (DM) in humans and cats and consist of a 37-amino-acid polypeptide known as islet amyloid polypeptide (IAPP). In order to find an explanation for the situation that islet amyloid (IA) does not develop in common rodent species, we have deduced the amino acid sequence of the IAPP molecule in mouse, rat and hamster. We find that a specific region of the molecule diverges to a high degree. Synthetic peptides corresponding to this region of human and hamster IAPP were compared for their ability to form amyloid fibrils in vitro. Whereas the human peptide readily formed fibrils with amyloid character, the hamster peptide completely lacked this property. We suggest this to be a likely explanation for the differences in IA formation between humans and rodents and discuss our findings in relation to the type 2 DM syndrome.
Betsholtz
C
C
Department of Pathology, University Hospital, Uppsala, Sweden.
Christmansson
L
L
Engström
U
U
Rorsman
F
F
Svensson
V
V
Johnson
K H
KH
Westermark
P
P
D000595:Amino Acid Sequence; D000682:Amyloid / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D007340:Insulinoma; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010179:Pancreas / Q000032:analysis; D010190:Pancreatic Neoplasms; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D014407:Tumor Cells, Cultured
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D012333:RNA, Messenger; D004247:DNA