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Major metabolic homocysteine-derivative, homocysteine thiolactone, exerts changes in pancreatic beta-cell glucose-sensing, cellular signal transduction and integrity

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Patterson, Steven, Flatt, Peter and McClenaghan, Neville (2007) Major metabolic homocysteine-derivative, homocysteine thiolactone, exerts changes in pancreatic beta-cell glucose-sensing, cellular signal transduction and integrity. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 461 (2). pp. 287-293. [Journal article]

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DOI: 10.1016/j.abb.2007.02.011

Abstract

Homocysteine can be converted to its reactive thioester, homocysteine thiolactone. Cytotoxic properties of these amino thiols have been attributed to protein homocysteinylation, increased oxidative stress, DNA damage and apoptosis. This study used pancreatic BRIN-BD11 beta-cells to examine functional defects caused by acute and long-term exposure to homocysteine thiolactone in comparison with homocysteine. Acute and long-term exposure to both agents caused concentration-dependent inhibitions of glucose-induced insulin secre- tion while impairing the insulin-secretory responses to alanine, KCl, elevated Ca2+ forskolin and PMA. Acute exposures also caused significant reduction in the amplitude of KCl-induced membrane depolarisation but no effects on changes of intracellular Ca2+ induced by alanine or KCL Cellular insulin content and DNA damage were not altered following culture, however, there were early signs of apoptosis consistent with impaired cellular integrity. In conclusion, exposure to homocysteine thiolactone, like homocysteine, induced beta P-cell dysfunction and demise by mechanisms independent of changes in membrane potential and [Ca2+](i). (C) 2007 Elsevier Inc. All rights reserved.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:2945
Deposited By:Professor Peter Flatt
Deposited On:17 Dec 2009 11:51
Last Modified:15 Jun 2011 11:10

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