Osteoprotegerin induces morphological and functional alterations in mouse pancreatic islets

Barbara Toffoli, Stella Bernardi, Riccardo Candido, Nicoletta Sabato, Renzo Carretta, Federica Corallini, Paola Secchiero, Giorgio Zauli, Bruno Fabris

Research output: Contribution to journalArticle

Abstract

Although serum osteoprotegerin (OPG) is significantly increased in diabetic subjects, its potential role in beta cell dysfunction has not been investigated. This study aimed to assess the effect of full-length OPG administered in vivo in mice on pancreatic islet structure and function and its interaction with the renin-angiotensin system (RAS).OPG-treated mice showed increased islet monocyte/macrophage infiltration, fibrosis and apoptosis with reduction of islet function. The remodeling of islet architecture was associated with increased pancreatic expression of components of the RAS, growth factor genes (transforming growth factor β and connective tissue growth factor) and inflammatory molecules (monocyte chemotactic protein-1 and vascular adhesion molecule type 1). Prevention of these changes with improvement of insulin secretion was observed in ramipril treated animals. Our data suggest that OPG might play an important role in promoting beta cell dysfunction and that the upregulation of the local RAS represents one possible mechanism responsible for the OPG-induced beta cell dysfunction.

Original languageEnglish
Pages (from-to)136-142
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume331
Issue number1
DOIs
Publication statusPublished - Jan 1 2011

Keywords

  • Angiotensin converting enzyme inhibitor
  • Diabetes
  • Osteoprotegerin
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

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  • Cite this

    Toffoli, B., Bernardi, S., Candido, R., Sabato, N., Carretta, R., Corallini, F., Secchiero, P., Zauli, G., & Fabris, B. (2011). Osteoprotegerin induces morphological and functional alterations in mouse pancreatic islets. Molecular and Cellular Endocrinology, 331(1), 136-142. https://doi.org/10.1016/j.mce.2010.08.019