|
|
Back
Canine
IAPP cDNA sequence provides important clues regarding diabetogenesis and
amyloidogenesis in type 2 diabetes
K Jordan, M P Murtaugh, T D O'Brien, P Westermark, C Betsholtz, K H
Johnson Abstract
broadcast on www.provet.co.uk
|
This information is provided by
Provet for educational purposes only.
You should seek the advice of your
veterinarian if your pet is ill as only he or she can correctly advise on the
diagnosis and recommend the treatment that is most appropriate for your pet.
Abstract
Islet amyloid polypeptide (IAPP) is a recently discovered pancreatic islet
hormone which is stored with insulin in beta cell granules. IAPP may have a
significant role in the development of Type 2 diabetes mellitus due to its
propensity to form islet cell-disrupting amyloid deposits, and by opposing the
action of insulin in peripheral tissues. Most evidence to-date suggests that
an intrinsic structural motif of IAPP is linked to the amyloidogenicity of
IAPP, and that this motif occurs only in those species (e.g., humans and cats)
that also develop age-associated or Type 2 diabetes We utilized polymerase
chain reaction methodology in this study to obtain the IAPP nucleotide and
protein sequences of the dog, a species not known to develop islet amyloid. We
show that dog IAPP contains the same putative amyloidogenic sequence (GAILS)
at residues 24-28 as human and cat IAPP, and that although dogs do not develop
islet amyloid they do develop IAPP-derived amyloid in association with
neoplastic beta cells (i.e., insulinomas). These results provide strong
evidence that the amyloidogenicity of IAPP is linked to at least two
prerequisites: a species-specific amyloidogenic structural motif, and
aberrations in the synthesis (or processing) of IAPP which leads to increased
concentration of IAPP in the local milieau.
Reference
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS ,
169(2):502-508 1990
Updated January 2016
|