An in vitro model of early islet amyloid polypeptide (IAPP) fibrillogenesis using human IAPP-transgenic mouse islets

M. S. Henson, B. L. Buman, K. Jordan, E. P. Rahrmann, R. M. Hardy, K. H. Johnson, Timothy D. O'Brien

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The mechanisms underlying insufficient insulin secretion and loss of β-cell mass in feline and human type 2 diabetes mellitus are incompletely understood. However, islet amyloid polypeptide (IAPP)-derived islet amyloidosis (IA) has been linked to increased rates of β-cell apoptosis and, therefore, our goal was to develop an in vitro model of IAPP fibrillogenesis using isolated pancreatic islets from mice transgenic for human IAPP (hIAPP Tg mice). Islets from hIAPP Tg mice, from mice transgenic for non-amyloidogenic murine IAPP (mIAPP Tg mice), and from the FVB background strain were exposed to normal (5.5 mM) or high (28 mM) glucose conditions in cell culture for 8 days. On days 0 and 8, islets were collected for electron microscopy (EM). EM showed no abnormalities in the mIAPP Tg or FVB islets at either time point. On day 8, hIAPP Tg islets cultured at high glucose concentration formed extracellular IAPP-derived flocculent deposits. No significant differences in rates of apoptosis were found between groups. Our findings, therefore, show that in vitro culture of hIAPP Tg mouse islets under high glucose conditions produces a readily available and rapidly inducible model of IAPP-derived fibrillogenesis and enables the study of early phases of the molecular pathogenesis of IA.

Original languageEnglish (US)
Pages (from-to)250-259
Number of pages10
JournalAmyloid
Volume13
Issue number4
DOIs
StatePublished - Dec 1 2006

Bibliographical note

Funding Information:
This work was supported in part by the Taylor Foundation.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

  • Amyloid
  • Islet amyloid
  • Islet amyloid polypeptide
  • Type 2 diabetes mellitus

Fingerprint Dive into the research topics of 'An in vitro model of early islet amyloid polypeptide (IAPP) fibrillogenesis using human IAPP-transgenic mouse islets'. Together they form a unique fingerprint.

Cite this