Amyloid formation in human islets is enhanced by heparin and inhibited by heparinase.

Autor:	Potter KJ; Departments of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Werner I; Departments of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Denroche HC; Departments of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Montane J; Departments of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Plesner A; Departments of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Chen Y; Department of Medical Biophysics, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, ON, Canada., Lei D; Departments of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Soukhatcheva G; Departments of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Warnock GL; Surgery, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada., Oberholzer J; Surgery, and Bioengineering, University of Illinois, Chicago, IL., Fraser PE; Department of Medical Biophysics, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, ON, Canada., Verchere CB; Departments of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.; Surgery, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
Jazyk:	angličtina
Zdroj:	American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2015 Jun; Vol. 15 (6), pp. 1519-30. Date of Electronic Publication: 2015 Apr 01.
DOI:	10.1111/ajt.13134
Abstrakt:	Islet transplantation is a promising therapy for patients with diabetes, but its long-term success is limited by many factors, including the formation of islet amyloid deposits. Heparin is employed in clinical islet transplantation to reduce clotting but also promotes fibrillization of amyloidogenic proteins. We hypothesized that heparin treatment of islets during pre-transplant culture may enhance amyloid formation leading to beta cell loss and graft dysfunction. Heparin promoted the fibrillization of human islet amyloid polypeptide (IAPP) and enhanced its toxicity to INS-1 beta cells. Heparin increased amyloid deposition in cultured human islets, but surprisingly decreased islet cell apoptosis. Treatment of human islets with heparin prior to transplantation increased the likelihood of graft failure. Removal of islet heparan sulfate glycosaminoglycans, which localize with islet amyloid deposits in type 2 diabetes, by heparinase treatment decreased amyloid deposition and protected against islet cell death. These findings raise the possibility that pretransplant treatment of human islets with heparin could potentiate IAPP aggregation and amyloid formation and may be detrimental to subsequent graft function. (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze:	MEDLINE
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