Homocysteine and other structurally-diverse amino thiols can alter pancreatic beta cell function without evoking cellular damage

Steven Patterson, Peter Flatt, Neville McClenaghan

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Homocysteine and related amino thiols, homocysteic acid, cysteic acid, homocysteine sulphinic acid and cysteine sulphinic acid have been labelled as neurotoxins. Homocysteine thiolactone, a metabolic derivative of homocysteine, is cytotoxic to endothelial cells and other cell lineages. Since pancreatic beta cells share many phenotypic similarities with neuronal cells, the present study uses clonal pancreatic BRiN-BD11 cells to investigate possible detrimental effects of these amino thiols on insulin secretion and pancreatic beta cell function. Insulin secretion was concentration-dependently inhibited at both basal (1.1 mM) and stimulatory (16.7 mM) glucose by homocysteine, homocysteine thiolactone and homocysteine sulphinic acid. Cysteic acid concentration-dependently inhibited insulin secretion at 16.7 mM glucose. Cell viability was not compromised by any of the amino thiols. Insulin secretory responses to alanine were inhibited by homocysteine, homocysteine thiolactone, homocysteic acid and cysteic acid. Insulin secretion in the presence of elevated Ca2+ and forskolin were lowered by all amino thiols, except homocysteic acid. The secretory responsiveness to PMA, GLP-1 and KCl were only impaired in the presence of homocysteine and homocysteine thiolactone. These findings indicate that homocysteine, homocysteine thiolactone and, to a lesser extent, other amino thiols cause dysfunctional insulin secretion from pancreatic beta cells. (c) 2006 Elsevier B.V. All rights reserved.
LanguageEnglish
Pages1109-1114
JournalBIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
Volume1760
Issue number7
DOIs
Publication statusPublished - Jul 2006

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Insulin-Secreting Cells
Homocysteine
Sulfhydryl Compounds
Cysteic Acid
Insulin
Glucose
Glucagon-Like Peptide 1
Neurotoxins
Cell Lineage
Colforsin
Alanine
Cell Survival
Endothelial Cells
homocysteine thiolactone
homocysteic acid

Cite this

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title = "Homocysteine and other structurally-diverse amino thiols can alter pancreatic beta cell function without evoking cellular damage",
abstract = "Homocysteine and related amino thiols, homocysteic acid, cysteic acid, homocysteine sulphinic acid and cysteine sulphinic acid have been labelled as neurotoxins. Homocysteine thiolactone, a metabolic derivative of homocysteine, is cytotoxic to endothelial cells and other cell lineages. Since pancreatic beta cells share many phenotypic similarities with neuronal cells, the present study uses clonal pancreatic BRiN-BD11 cells to investigate possible detrimental effects of these amino thiols on insulin secretion and pancreatic beta cell function. Insulin secretion was concentration-dependently inhibited at both basal (1.1 mM) and stimulatory (16.7 mM) glucose by homocysteine, homocysteine thiolactone and homocysteine sulphinic acid. Cysteic acid concentration-dependently inhibited insulin secretion at 16.7 mM glucose. Cell viability was not compromised by any of the amino thiols. Insulin secretory responses to alanine were inhibited by homocysteine, homocysteine thiolactone, homocysteic acid and cysteic acid. Insulin secretion in the presence of elevated Ca2+ and forskolin were lowered by all amino thiols, except homocysteic acid. The secretory responsiveness to PMA, GLP-1 and KCl were only impaired in the presence of homocysteine and homocysteine thiolactone. These findings indicate that homocysteine, homocysteine thiolactone and, to a lesser extent, other amino thiols cause dysfunctional insulin secretion from pancreatic beta cells. (c) 2006 Elsevier B.V. All rights reserved.",
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Homocysteine and other structurally-diverse amino thiols can alter pancreatic beta cell function without evoking cellular damage. / Patterson, Steven; Flatt, Peter; McClenaghan, Neville.

In: BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, Vol. 1760, No. 7, 07.2006, p. 1109-1114.

Research output: Contribution to journalArticle

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