Laboratory of Inorganic Chemistry and Advanced Materials, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Division of Clinical and Molecular Endocrinology, 1(st) Department of Internal Medicine, AHEPA, University Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
J Inorg Biochem. 2018 Sep;186:217-227. doi: 10.1016/j.jinorgbio.2018.04.020. Epub 2018 May 1.
Diabetes mellitus comprises a group of metabolic abnormalities due to insulin deficiency and/or resistance. Obesity contributes to diabetes, with a strong causal relationship existing between diabetes and insulin resistance, especially in patients with Diabetes mellitus II. Adipocytes emerge as key constituents of adipose tissue physiology. In their pre-mature form to mature state transformation, adipocytes fully exemplify one of the key adipogenic actions of insulin. Poised to a) gain insight into adipogenesis leading to antidiabetic factors, and b) investigate adipogenesis through careful examination of insulin contributions to interwoven mechanistic pathways, a systematic comparative study was launched involving well-defined metal-citrates (zinc and vanadium), the chemical reactivity of which was in line with their chemistry under physiological conditions. Selection of the specific compounds was based on their common aqueous coordination chemistry involving the physiological chelator citric acid. Cellular maturation of pre-adipocytes to their mature form was pursued in the presence-absence of insulin and employment of closely linked genetic targets, key to adipocyte maturation (Peroxisome proliferator-activated receptor gamma (PPAR-γ), Glucose transporter 1,3,4 (GLUT 1,3,4), Adiponectin (ADIPOQ), Glucokinase (GCK), and Insulin receptor (INS-R)). The results show a) distinct adipogenic biological profiles for the metalloforms involved in a dose-, time- and nature-dependent manner, and b) metal ion-specific adipogenic response-signals at the same or higher level than insulin toward all selected targets. Collectively, the foundations have been established for future exploitation of the distinct metal-specific adipogenic factors contributing to the functional maturation of adipose tissue and their use toward hyperglycemic control in Diabetes mellitus.
糖尿病是一组由于胰岛素缺乏和/或抵抗引起的代谢异常。肥胖会导致糖尿病，糖尿病与胰岛素抵抗之间存在很强的因果关系，尤其是在 2 型糖尿病患者中。脂肪细胞是脂肪组织生理学的关键组成部分。在它们从早期形态向成熟状态的转化过程中，脂肪细胞充分体现了胰岛素的关键脂肪生成作用之一。为了 a) 深入了解导致抗糖尿病因子的脂肪生成，以及 b) 通过仔细研究胰岛素对交织的机制途径的贡献来研究脂肪生成，我们开展了一项系统的比较研究，涉及定义明确的金属柠檬酸（锌和钒），其化学反应性与其在生理条件下的化学性质相符。选择特定化合物的依据是它们常见的涉及生理螯合剂柠檬酸的水合配位化学。在存在或不存在胰岛素的情况下，使用与脂肪细胞成熟密切相关的遗传靶标（过氧化物酶体增殖物激活受体γ（PPAR-γ）、葡萄糖转运蛋白 1、3、4（GLUT 1、3、4）、脂联素（ADIPOQ）、葡糖激酶（GCK）和胰岛素受体（INS-R）），研究前脂肪细胞向成熟形态的细胞成熟。结果表明：a）金属形态以剂量、时间和性质依赖的方式表现出独特的脂肪生成生物学特征；b）金属离子特异性的脂肪生成信号在相同或高于胰岛素水平，对所有选定的靶标都有反应。总的来说，为未来利用有助于脂肪组织功能成熟的独特金属特异性脂肪生成因子以及将其用于糖尿病的高血糖控制奠定了基础。
