Effects of cross-link breakers, glycation inhibitors and insulin sensitisers on HDL function and the non-enzymatic glycation of apolipoprotein A-I

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Effects of cross-link breakers, glycation inhibitors and insulin sensitisers on HDL function and the non-enzymatic glycation of apolipoprotein A-I. / Nobecourt, E.; Zeng, J.; Davies, M. J.; Brown, B. E.; Yadav, S.; Barter, P. J.; Rye, K. -A.

In: Diabetologia, Vol. 51, No. 6, 06.2008, p. 1008-1017.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Nobecourt, E, Zeng, J, Davies, MJ, Brown, BE, Yadav, S, Barter, PJ & Rye, K-A 2008, 'Effects of cross-link breakers, glycation inhibitors and insulin sensitisers on HDL function and the non-enzymatic glycation of apolipoprotein A-I', Diabetologia, vol. 51, no. 6, pp. 1008-1017. https://doi.org/10.1007/s00125-008-0986-z

APA

Nobecourt, E., Zeng, J., Davies, M. J., Brown, B. E., Yadav, S., Barter, P. J., & Rye, K. -A. (2008). Effects of cross-link breakers, glycation inhibitors and insulin sensitisers on HDL function and the non-enzymatic glycation of apolipoprotein A-I. Diabetologia, 51(6), 1008-1017. https://doi.org/10.1007/s00125-008-0986-z

Vancouver

Nobecourt E, Zeng J, Davies MJ, Brown BE, Yadav S, Barter PJ et al. Effects of cross-link breakers, glycation inhibitors and insulin sensitisers on HDL function and the non-enzymatic glycation of apolipoprotein A-I. Diabetologia. 2008 Jun;51(6):1008-1017. https://doi.org/10.1007/s00125-008-0986-z

Author

Nobecourt, E. ; Zeng, J. ; Davies, M. J. ; Brown, B. E. ; Yadav, S. ; Barter, P. J. ; Rye, K. -A. / Effects of cross-link breakers, glycation inhibitors and insulin sensitisers on HDL function and the non-enzymatic glycation of apolipoprotein A-I. In: Diabetologia. 2008 ; Vol. 51, No. 6. pp. 1008-1017.

Bibtex

@article{f297b5c9847c4372becf3e083a45a30a,
title = "Effects of cross-link breakers, glycation inhibitors and insulin sensitisers on HDL function and the non-enzymatic glycation of apolipoprotein A-I",
abstract = "Aims/hypothesis Hyperglycaemia, a key feature of diabetes, is associated with non-enzymatic glycation of plasma proteins. We have shown previously that the reactive alpha-oxoaldehyde, methylglyoxal, non-enzymatically glycates apolipoprotein (Apo)A-I, the main apolipoprotein of HDL, and prevents it from activating lecithin:cholesterol acyltransferase (LCAT), the enzyme that generates almost all of the cholesteryl esters in plasma. This study investigates whether the glycation inhibitors aminoguanidine and pyridoxamine, the insulin sensitiser metformin and the cross-link breaker alagebrium can inhibit and/or reverse the methylglyoxal-mediated glycation of ApoA-I and whether these changes can preserve or restore the ability of ApoA-I to activate LCAT.Methods Inhibition of ApoA-I glycation was assessed by incubating aminoguanidine, pyridoxamine, metformin and alagebrium with mixtures of methylglyoxal and discoidal reconstituted HDL (rHDL) containing phosphatidylcholine and ApoA-I, ([A-I]rHDL). Glycation was assessed as the modification of ApoA-I arginine, lysine and tryptophan residues, and by the extent of ApoA-I cross-linking. The reversal of ApoA-I glycation was investigated by pre-incubating discoidal (A-I)rHDL with methylglyoxal, then incubating the modified rHDL with aminoguanidine, pyridoxamine or alagebrium.Results Aminoguanidine, pyridoxamine, metformin and alagebrium all decreased the methylglyoxal-mediated glycation of the ApoA-I in discoidal rHDL and conserved the ability of the particles to act as substrates for LCAT. However, neither aminoguanidine, pyridoxamine nor alagebrium could reverse the glycation of ApoA-I or restore its ability to activate LCAT.Conclusions/'interpretation Glycation inhibitors, insulin sensitisers and cross-link breakers are important for preserving normal HDL function in diabetes.",
keywords = "alagebrium, aminoguanidine, ApoA-I, apolipoprotein A-I, glycation, HDL, LCAT, lecithin, cholesterol acyltransferase, metformin, pyridoxamine, HIGH-DENSITY-LIPOPROTEINS, END-PRODUCTS, ENDOTHELIAL FUNCTION, CHOLESTEROL, PYRIDOXAMINE, METFORMIN, GLUCOSE, AMINOGUANIDINE, PARTICLES, PROTEINS",
author = "E. Nobecourt and J. Zeng and Davies, {M. J.} and Brown, {B. E.} and S. Yadav and Barter, {P. J.} and Rye, {K. -A.}",
year = "2008",
month = jun,
doi = "10.1007/s00125-008-0986-z",
language = "English",
volume = "51",
pages = "1008--1017",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer",
number = "6",

}

RIS

TY - JOUR

T1 - Effects of cross-link breakers, glycation inhibitors and insulin sensitisers on HDL function and the non-enzymatic glycation of apolipoprotein A-I

AU - Nobecourt, E.

AU - Zeng, J.

AU - Davies, M. J.

AU - Brown, B. E.

AU - Yadav, S.

AU - Barter, P. J.

AU - Rye, K. -A.

PY - 2008/6

Y1 - 2008/6

N2 - Aims/hypothesis Hyperglycaemia, a key feature of diabetes, is associated with non-enzymatic glycation of plasma proteins. We have shown previously that the reactive alpha-oxoaldehyde, methylglyoxal, non-enzymatically glycates apolipoprotein (Apo)A-I, the main apolipoprotein of HDL, and prevents it from activating lecithin:cholesterol acyltransferase (LCAT), the enzyme that generates almost all of the cholesteryl esters in plasma. This study investigates whether the glycation inhibitors aminoguanidine and pyridoxamine, the insulin sensitiser metformin and the cross-link breaker alagebrium can inhibit and/or reverse the methylglyoxal-mediated glycation of ApoA-I and whether these changes can preserve or restore the ability of ApoA-I to activate LCAT.Methods Inhibition of ApoA-I glycation was assessed by incubating aminoguanidine, pyridoxamine, metformin and alagebrium with mixtures of methylglyoxal and discoidal reconstituted HDL (rHDL) containing phosphatidylcholine and ApoA-I, ([A-I]rHDL). Glycation was assessed as the modification of ApoA-I arginine, lysine and tryptophan residues, and by the extent of ApoA-I cross-linking. The reversal of ApoA-I glycation was investigated by pre-incubating discoidal (A-I)rHDL with methylglyoxal, then incubating the modified rHDL with aminoguanidine, pyridoxamine or alagebrium.Results Aminoguanidine, pyridoxamine, metformin and alagebrium all decreased the methylglyoxal-mediated glycation of the ApoA-I in discoidal rHDL and conserved the ability of the particles to act as substrates for LCAT. However, neither aminoguanidine, pyridoxamine nor alagebrium could reverse the glycation of ApoA-I or restore its ability to activate LCAT.Conclusions/'interpretation Glycation inhibitors, insulin sensitisers and cross-link breakers are important for preserving normal HDL function in diabetes.

AB - Aims/hypothesis Hyperglycaemia, a key feature of diabetes, is associated with non-enzymatic glycation of plasma proteins. We have shown previously that the reactive alpha-oxoaldehyde, methylglyoxal, non-enzymatically glycates apolipoprotein (Apo)A-I, the main apolipoprotein of HDL, and prevents it from activating lecithin:cholesterol acyltransferase (LCAT), the enzyme that generates almost all of the cholesteryl esters in plasma. This study investigates whether the glycation inhibitors aminoguanidine and pyridoxamine, the insulin sensitiser metformin and the cross-link breaker alagebrium can inhibit and/or reverse the methylglyoxal-mediated glycation of ApoA-I and whether these changes can preserve or restore the ability of ApoA-I to activate LCAT.Methods Inhibition of ApoA-I glycation was assessed by incubating aminoguanidine, pyridoxamine, metformin and alagebrium with mixtures of methylglyoxal and discoidal reconstituted HDL (rHDL) containing phosphatidylcholine and ApoA-I, ([A-I]rHDL). Glycation was assessed as the modification of ApoA-I arginine, lysine and tryptophan residues, and by the extent of ApoA-I cross-linking. The reversal of ApoA-I glycation was investigated by pre-incubating discoidal (A-I)rHDL with methylglyoxal, then incubating the modified rHDL with aminoguanidine, pyridoxamine or alagebrium.Results Aminoguanidine, pyridoxamine, metformin and alagebrium all decreased the methylglyoxal-mediated glycation of the ApoA-I in discoidal rHDL and conserved the ability of the particles to act as substrates for LCAT. However, neither aminoguanidine, pyridoxamine nor alagebrium could reverse the glycation of ApoA-I or restore its ability to activate LCAT.Conclusions/'interpretation Glycation inhibitors, insulin sensitisers and cross-link breakers are important for preserving normal HDL function in diabetes.

KW - alagebrium

KW - aminoguanidine

KW - ApoA-I

KW - apolipoprotein A-I

KW - glycation

KW - HDL

KW - LCAT

KW - lecithin

KW - cholesterol acyltransferase

KW - metformin

KW - pyridoxamine

KW - HIGH-DENSITY-LIPOPROTEINS

KW - END-PRODUCTS

KW - ENDOTHELIAL FUNCTION

KW - CHOLESTEROL

KW - PYRIDOXAMINE

KW - METFORMIN

KW - GLUCOSE

KW - AMINOGUANIDINE

KW - PARTICLES

KW - PROTEINS

U2 - 10.1007/s00125-008-0986-z

DO - 10.1007/s00125-008-0986-z

M3 - Journal article

VL - 51

SP - 1008

EP - 1017

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 6

ER -

ID: 314392263