Detrimental actions of metabolic syndrome risk factor, homocysteine, on pancreatic beta-cell glucose metabolism and insulin secretion

The Journal of Endocrinology
S PattersonN H McClenaghan

Abstract

Elevated plasma homocysteine has been reported in individuals with diseases of the metabolic syndrome including vascular disease and insulin resistance. As homocysteine exerts detrimental effects on endothelial and neuronal cells, this study investigated effects of acute homocysteine exposure on beta-cell function and insulin secretion using clonal BRIN-BD11 beta-cells. Acute insulin release studies in the presence of various test reagents were performed using monolayers of BRIN-BD11 cells and samples assayed by insulin radioimmunoassay. Cellular glucose metabolism was assessed by nuclear magnetic resonance (NMR) analysis following 60-min exposure of BRIN-BD11 cell monolayers to glucose in either the absence or presence of homocysteine. Homocysteine dose-dependently inhibited insulin release at moderate and stimulatory glucose concentrations. This inhibitory effect was reversible at all but the highest concentration of homocysteine. 13C-glucose NMR demonstrated decreased labelling of glutamate from glucose at positions C2, C3 and C4, indicating that the tricarboxylic acid (TCA) cycle-dependent glucose metabolism was reduced in the presence of homocysteine. Homocysteine also dose-dependently inhibited insulinotropic responses to...Continue Reading

Citations

May 12, 2010·International Journal of Clinical Practice·I S Young, J V Woodside
May 15, 2012·The Journal of Endocrinology·S M ScullionN H McClenaghan
Aug 24, 2011·Journal of Nutrigenetics and Nutrigenomics·Greg C SmithLynnette R Ferguson
Aug 7, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alexander J NashKourosh R Ahmadi
Nov 8, 2006·Diabetes/metabolism Research and Reviews·Steven PattersonNeville H McClenaghan
May 18, 2016·Journal of Diabetes Investigation·Tian GongYun Wang
Oct 25, 2007·Biochemical Society Transactions·P NewsholmeL Brennan
Oct 17, 2019·Postgraduate Medicine·Pavlina A Andreeva-GatevaIvanka I Dimova
Jan 8, 2019·The American Journal of Clinical Nutrition·Mads Vendelbo LindJane Nygaard Eriksen
Aug 28, 2019·Journal of Clinical Medicine·Irene Hoyas, Miguel Leon-Sanz
Mar 24, 2017·Diabetology & Metabolic Syndrome·Daniel E PlattPierre A Zalloua
Oct 31, 2018·International Journal of Molecular Sciences·Jasmine F PlowsMark H Vickers
Dec 22, 2015·European Journal of Pharmacology·Steven PattersonNeville H McClenaghan

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