4 years ago

The toxic nature of murine amylin and the immune responsivity of pancreatic islet to conformational antibody in mice

C. M., Jotha-Mattos, Pascarelli, Lima, L., B. M. O., L. C. S., Souza, Erthal, Reis, L. M. T. R., Lara, K. L. A., Costa, S. A., F. A.
The human amylin is a pancreatic peptide hormone cosecreted with amylin and found in hyperhormonemic state along with insulin in subclinical diabetes. Amylin has been associated with the pathology of type 2 diabetes, particularly due to its ability to assembly into toxic oligomers and amyloid speciments. On the other hand, some variants such as murine amylin has been described as non amyloidogenic, either in vitro or in vivo. Recent data have demonstrated the amyloid propensity of murine amylin and the therapeutic analogue pramlintide, suggesting a universality for amylin amyloidosis. Here we report the amyloidogenesis of murine amylin, which showed lower responsivity to the fluorescent probe thioflavin T compared to human amylin, but presented highly organized fibrilar amyloid material. The aggregation of murine amylin also resulted in the formation of cytotoxic specimens, as evaluated in vitro in INS-1 cells. The aggregation product from murine amylin was responsive to a specific antibody raised against amyloid oligomers, the A11 oligomer antibody. Pancreatic islets of swiss mice have also shown responsivity for the anti-oligomer, suggesting the natural abundance of such specimen in rodents. These data provide for the first time evidences for the toxic nature of oligomeric assemblies of murine amylin and its detection in non-transgenic mice.

Publisher URL: http://biorxiv.org/cgi/content/short/175539v1

DOI: 10.1101/175539

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