Evidence that Differences in Fructosamine-3-Kinase Activity May be Associated with the Glycation Gap in Human Diabetes

2.50
Hdl Handle:
http://hdl.handle.net/2436/620826
Title:
Evidence that Differences in Fructosamine-3-Kinase Activity May be Associated with the Glycation Gap in Human Diabetes
Authors:
Dunmore, Simon J; Al-Derawi, Amr S; Nayak, Ananth U; Narshi, Aruna; Nevill, Alan M; Hellwig, Anne; Majebi, Andrew; Kirkham, Paul; Brown, James E; Singh, Baldev M
Abstract:
The phenomenon of a discrepancy between glycated haemoglobin levels and other indicators of average glycaemia may be due to many factors but can be measured as the glycation gap (GGap). This GGap is associated with differences in complications in patients with diabetes and may possibly be explained by dissimilarities in deglycation in turn leading to altered production of Advanced Glycation End (AGE) products. We hypothesised that variations in the level of the deglycating enzyme Fructosamine-3-kinase (FN3K) might be associated with the GGap. We measured erythrocyte FN3K concentrations and enzyme activity in a population dichotomised for a large positive or negative GGap. FN3K protein was higher and we found a striking 3-fold greater activity (323%) at any given FN3K protein level in the erythrocytes of the negative compared with positive GGap groups. This was associated with lower AGE levels in the negative GGap group (79%), lower pro-inflammatory adipokines (Leptin/Adiponectin ratio) (73%) and much lower pro-thrombotic PAI-1 levels (19%). We conclude that FN3K may play a key role in the GGap and thus diabetes complications such that FN3K may be potential predictor of the risk of diabetes complications. Pharmacological modifications of its activity may provide a novel approach to their prevention.
Citation:
Evidence that Differences in Fructosamine-3-Kinase Activity May be Associated with the Glycation Gap in Human Diabetes 2017:db170441 Diabetes
Publisher:
American Diabetes Association
Journal:
Diabetes
Issue Date:
24-Oct-2017
URI:
http://hdl.handle.net/2436/620826
DOI:
10.2337/db17-0441
Additional Links:
http://diabetes.diabetesjournals.org/lookup/doi/10.2337/db17-0441
Type:
Article
Language:
en
ISSN:
1939-327X
Appears in Collections:
School of Biomedical Sciences and Physiology

Full metadata record

DC FieldValue Language
dc.contributor.authorDunmore, Simon Jen
dc.contributor.authorAl-Derawi, Amr Sen
dc.contributor.authorNayak, Ananth Uen
dc.contributor.authorNarshi, Arunaen
dc.contributor.authorNevill, Alan Men
dc.contributor.authorHellwig, Anneen
dc.contributor.authorMajebi, Andrewen
dc.contributor.authorKirkham, Paulen
dc.contributor.authorBrown, James Een
dc.contributor.authorSingh, Baldev Men
dc.date.accessioned2017-11-08T11:46:20Z-
dc.date.available2017-11-08T11:46:20Z-
dc.date.issued2017-10-24-
dc.identifier.citationEvidence that Differences in Fructosamine-3-Kinase Activity May be Associated with the Glycation Gap in Human Diabetes 2017:db170441 Diabetesen
dc.identifier.issn1939-327Xen
dc.identifier.doi10.2337/db17-0441-
dc.identifier.urihttp://hdl.handle.net/2436/620826-
dc.description.abstractThe phenomenon of a discrepancy between glycated haemoglobin levels and other indicators of average glycaemia may be due to many factors but can be measured as the glycation gap (GGap). This GGap is associated with differences in complications in patients with diabetes and may possibly be explained by dissimilarities in deglycation in turn leading to altered production of Advanced Glycation End (AGE) products. We hypothesised that variations in the level of the deglycating enzyme Fructosamine-3-kinase (FN3K) might be associated with the GGap. We measured erythrocyte FN3K concentrations and enzyme activity in a population dichotomised for a large positive or negative GGap. FN3K protein was higher and we found a striking 3-fold greater activity (323%) at any given FN3K protein level in the erythrocytes of the negative compared with positive GGap groups. This was associated with lower AGE levels in the negative GGap group (79%), lower pro-inflammatory adipokines (Leptin/Adiponectin ratio) (73%) and much lower pro-thrombotic PAI-1 levels (19%). We conclude that FN3K may play a key role in the GGap and thus diabetes complications such that FN3K may be potential predictor of the risk of diabetes complications. Pharmacological modifications of its activity may provide a novel approach to their prevention.en
dc.language.isoenen
dc.publisherAmerican Diabetes Associationen
dc.relation.urlhttp://diabetes.diabetesjournals.org/lookup/doi/10.2337/db17-0441en
dc.rightsArchived with thanks to Diabetesen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleEvidence that Differences in Fructosamine-3-Kinase Activity May be Associated with the Glycation Gap in Human Diabetesen
dc.typeArticleen
dc.identifier.journalDiabetesen
dc.date.accepted2017-10-
rioxxterms.funderInternalen
rioxxterms.identifier.projectUoW081117SDen
rioxxterms.versionAMen
rioxxterms.licenseref.urihttps://creativecommons.org/CC BY-NC-ND 4.0en
rioxxterms.licenseref.startdate2018-10-24en
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