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

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)502-508
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume169
Issue number2
DOIs
StatePublished - Jun 15 1990

Bibliographical note

Funding Information:
ACKNOWLEDGMENTS: This study was supported by Grant ROl DK36734 of the National Institute of Diabetes and Digestive and Kidney Disease, the Swedish Medical Research Council (Project Nos. 5941 & 9041), the Research Fund of King Gustaf V, the Nordic Insulin Fund, Louis-Hansen’s Memorial Fund, Hans von Kanttow’s Foundation, Magnus Bergwall’s Foundation, and the Swedish National Board for Technical Development.

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