Homocysteine-induced impairment of insulin secretion from clonal pancreatic BRIN-BD11 beta-cells is not prevented by catalase

Steven Patterson, Peter Flatt, Neville McClenaghan

Research output: Contribution to journalArticlepeer-review


Objectives: Although detrimental effects of homocysteine attributed to homocysteine auto-oxidation and generation of hydrogen peroxide (H2O2) have been reported in various cell types, such actions have not been considered in pancreatic beta-cells. This study investigates the acute effects of homocysteine on beta-cell integrity and regulation, in particular, the role of H2O2 generated by auto-oxidation. Methods: Assessment of beta-cell function was examined during acute 20- or 40-minute incubations with homocysteine using clonal BRIN-BD11 beta-cells. Results: Homocysteine (50-1000 mu mol/L) inhibited basal and glucose-induced insulin secretion in a concentration-dependent manner. Insulinotropic responses to alanine, arginine, 2-ketoisocaproate, elevate Ca2+ tolbutamide, potassium chloride (KCI), forskolin, and phorbol 12-myristate 13-acetate were also significantly reduced by homocysteine. Likewise, preincubation with homocysteine caused a reduction in the insulinotropic responses to glucose and each of the secretagogues tested. Notably, excess catalase (100 mu g/mL) in the buffer, although sufficient to remove homocysteine-derived 14202, did not alleviate the detrimental effects of homocysteine. Conclusions: Collectively, these data suggest that homocysteine impairs insulin secretory function by mechanisms independent of H2O2 generation. Although homocysteine may give rise to reactive oxygen species, these observations indicate detrimental nonoxidative pancreatic beta-cell actions of homocysteine.
Original languageEnglish
Pages (from-to)144-151
Issue number1
Publication statusPublished (in print/issue) - Jan 2007


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