RT Journal Article
SR Electronic
T1 Fructosamine-3-Kinase: A molecular link between COPD and diabetes regulating carbonyl stress and the impact of metformin treatment
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA886
DO 10.1183/13993003.congress-2015.PA886
VO 46
IS suppl 59
A1 Amr Alderawi
A1 Simon Dunmore
A1 Gaetano Caramori
A1 Andrew Hitchings
A1 Emma Baker
A1 Paul Kirkham
YR 2015
UL http://erj.ersjournals.com/content/46/suppl_59/PA886.abstract
AB There is a strong comorbid association between COPD and diabetes and linkage to a worsening clinical outcome in COPD. Oxidative stress leads to increased carbonyl stress in COPD as measured by increased levels of reactive carbonyls, levels of which are linked to severity of COPD. In diabetes increased levels of reactive carbonyls results in the formation of Advanced Glycation End Products (AGEs) the formation of which is reversed by an enzyme called Fructosamine-3-Kinase (FN3K). Low levels of expression and activity of this enzyme are linked to a higher incidence of diabetic complications. We therefore investigated the expression levels of FN3K in two separate clinical studies in COPD as this enzyme may be important in controlling the impact of carbonyl stress and possibly disease severity. We found that 83% of healthy subjects expressed FN3K at low levels in airway epithelial cells. In contrast, 75% of smokers exhibited a large significant increase in FN3K expression. Whereas, in COPD patients 67% had low levels of FN3K expression. Metformin treatment of AECOPD patients produced a significant increase (P < 0.0001) in mean FN3K level from 83.4ng/ml at baseline to 110.3ng/ml at discharge and remained elevated at follow up at 124.4ng/ml. In contrast the AECOPD patients administered the placebo showed no significant change. We conclude that FN3K expression is upregulated in smokers as a protective mechanism to limit the impact of increased carbonyl stress. In COPD, this protective mechanism is lost. Metformin treatment in AECOPD patients does however significantly increase FN3K expression thereby helping to potentially limit disease severity.