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

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.

Publication DOI: https://doi.org/10.2337/db17-0441
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > School of Biosciences > Cell & Tissue Biomedical Research
Additional Information: © 2017 by the American Diabetes Association. Funding: Wolverhampton Diabetes Trust.
Publication ISSN: 1939-327X
Last Modified: 13 May 2024 07:19
Date Deposited: 05 Jan 2018 14:45
Full Text Link:
Related URLs: https://www.sco ... 63fadee626bb85f (Scopus URL)
PURE Output Type: Article
Published Date: 2018-01-01
Published Online Date: 2017-10-24
Accepted Date: 2017-10-17
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 (ORCID Profile 0000-0002-3504-7373)
Singh, Baldev M

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