Ferret islet amyloid polypeptide (IAPP): characterization of in vitro and in vivo amyloidogenicity

Abstract

Diabetes in the domestic ferret (Mustela putorius furo) has previously been described and the purpose of this study was to evaluate if the ferret could serve as a model for the study of β-cell degeneration associated with formation of islet amyloid. The nucleotide and amino acid sequence of ferret islet amyloid polypeptide (IAPP) 1–37 was identified and the synthesized peptide was studied with regards to in vitro amyloidogenicity and potential cellular toxicity in a comparative approach to human, cat and the non-amyloidogenic rat IAPP. Ferret IAPP forms amyloid-like fibrils, but with a longer lag phase than human and cat IAPP and the aggregation process was shown to reduce cell viability of cultured β-cells, but with less potency than these two amyloidogenic counterparts. Immunohistochemistry of ferret pancreas confirmed IAPP expression in the islets of Langerhans, but no islet amyloid was found in a very limited sample size of one diabetic and five healthy ferrets. Islet amyloid has never been described in ferrets, and it is not possible to determine if it is due to lack of studies/material or to the fact that the ferret’s life span is too short to present with such pathology.

Keywords::

• Amylin
• cat
• electron microscopy
• islet of Langerhans
• islet amyloid
• thioflavin T
• type 2 diabetes

Acknowledgements

JFP would like to thank Novo Nordisk R&D science talent attraction and recruitment program for the Scandinavian return fellowship and Susanne Juul Rasmussen for tissue embedding and sectioning. The authors wish to thank Dr. Bruce Williams for sharing his experience on pancreas pathology in ferrets.

Declaration of interest: This work was funded by Novo Nordisk A/S. JFP, LS and KD are employed by Novo Nordisk A/S and by this mean the funder played a role in the study design, data collection, decision to publish and preparation of the manuscript. MOBB has no interests to declare.