Diabetes Research Group, Academic Institute of Medicine, University of Wolverhampton, Wolverhampton, U.K.
Department of Endocrinology and Diabetes, University Hospital of North Midlands NHS Trust, Stoke-on-Trent, U.K.
Diabetes. 2018 Jan;67(1):131-136. doi: 10.2337/db17-0441. Epub 2017 Oct 24.
The phenomenon of a discrepancy between glycated hemoglobin levels and other indicators of average glycemia 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 products (AGEs). We hypothesized 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 dichotomized for a large positive or negative GGap. FN3K protein was higher and we found a striking threefold greater activity (323%) at any given FN3K protein level in the erythrocytes of the negative-GGap group compared with the positive-GGap group. This was associated with lower AGE levels in the negative-GGap group (79%), lower proinflammatory adipokines (leptin-to-adiponectin ratio) (73%), and much lower prothrombotic 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 a potential predictor of the risk of diabetes complications. Pharmacological modifications of its activity may provide a novel approach to their prevention.
糖化血红蛋白水平与平均血糖其他指标之间的差异现象可能是由多种因素引起的，但可以通过糖化间隙 (GGap) 来衡量。这种 GGap 与糖尿病患者并发症的差异有关，其可能是由于不同的去糖化作用导致晚期糖基化终产物 (AGEs) 的产生发生改变。我们假设，去糖化酶果糖胺-3-激酶 (FN3K) 水平的变化可能与 GGap 有关。我们在红细胞中测量了 FN3K 浓度和酶活性，这些红细胞根据大的正或负 GGap 进行了二分法划分。FN3K 蛋白水平较高，我们发现负 GGap 组的 FN3K 蛋白水平在任何给定水平下的活性都显著高出三倍（323%），而正 GGap 组则不然。这与负 GGap 组的 AGE 水平较低（79%）、促炎脂肪因子（瘦素与脂联素比值）较低（73%）以及促血栓形成的 PAI-1 水平较低（19%）有关。我们得出结论，FN3K 可能在 GGap 中发挥关键作用，从而影响糖尿病并发症，因此 FN3K 可能是糖尿病并发症风险的潜在预测指标。对其活性进行药理学修饰可能为预防这些并发症提供一种新方法。
