Raza Ali, Mahmood Riaz, Habib Safia, Talha Mohd, Khan Shifa, Hashmi Md Amiruddin, Mohammad Taj, Ali Asif
Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
J Biomol Struct Dyn. 2023 Jul-Aug;41(12):5850-5862. doi: 10.1080/07391102.2022.2098820. Epub 2022 Jul 22.
Fructosylation of proteins results in the formation of advanced glycation end-products (AGEs). A diet rich in fructose along with hyperglycemia can cause fructose mediated glycation (fructosylation) of proteins, which results in AGEs formation. Insulin is a peptide hormone that is glycated when exposed to carbohydrates such as glucose. In this study, we have analysed the interaction of insulin with fructose and biophysically characterized fructose modified insulin. studies performed through molecular docking and molecular dynamics simulation revealed that fructose binds to insulin with strong affinity resulting in the formation of insulin-fructose complex. Fructosylation of insulin caused hyperchromicity, loss of intrinsic fluorescence, gain in AGEs specific fluorescence and elevated the carbonyl and fructosamine content. Enhanced thioflavin T fluorescence suggested the presence of fibrillar structures at higher concentrations of fructose. Electron microscopy revealed the formation of characteristic amorphous and amyloid like aggregates at lower and higher concentrations of fructose, respectively. These findings show that fructosylation of insulin causes AGEs production, aggregation and alters its gross structural integrity. These changes may reduce the biological activity of insulin that can aggravate conditions like type II diabetes mellitus.Communicated by Ramaswamy H. Sarma.
蛋白质的果糖基化会导致晚期糖基化终产物（AGEs）的形成。富含果糖的饮食加上高血糖会导致蛋白质发生果糖介导的糖基化（果糖基化），从而导致AGEs的形成。胰岛素是一种肽类激素，当暴露于葡萄糖等碳水化合物时会发生糖基化。在本研究中，我们分析了胰岛素与果糖的相互作用，并对果糖修饰的胰岛素进行了生物物理表征。通过分子对接和分子动力学模拟进行的研究表明，果糖以强亲和力与胰岛素结合，导致胰岛素-果糖复合物的形成。胰岛素的果糖基化导致增色效应、固有荧光丧失、AGEs特异性荧光增加，并提高了羰基和果糖胺含量。硫黄素T荧光增强表明在较高果糖浓度下存在纤维状结构。电子显微镜显示，在较低和较高果糖浓度下分别形成了特征性的无定形和淀粉样聚集体。这些发现表明，胰岛素的果糖基化会导致AGEs的产生、聚集，并改变其总体结构完整性。这些变化可能会降低胰岛素的生物活性，从而加重II型糖尿病等病症。由拉马斯瓦米·H·萨尔马传达。
