Tsave O, Yavropoulou M P, Kafantari M, Gabriel C, Yovos J G, Salifoglou A
Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
Division of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, AHEPA, University Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
J Inorg Biochem. 2016 Oct;163:323-331. doi: 10.1016/j.jinorgbio.2016.07.015. Epub 2016 Jul 27.
Insulin resistance is identified through numerous pathophysiological conditions, such as Diabetes mellitus II, obesity, hypertension and other metabolic syndromes. Enhancement of insulin action and\or its complete replacement by insulin-enhancing or insulin-mimetic agents seems to improve treatment of metabolic diseases. Over the last decades, intensive research has targeted the investigation of such agents, with chromium emerging as an important inorganic cofactor involved in the requisite metabolic chemistry. Chromium in its trivalent state has been shown to play a central role in carbohydrate metabolism by enhancing insulin signaling, action, and thus the sensitivity of insulin-sensitive tissues. A very likely link between diabetes and obesity is the adipose tissue, which stores energy in the form of triglycerides and releases free fatty acids. To date, there is paucity of information on the exact mechanism of the chromium effect concerning insulin-activated molecular paths, such as adipogenesis. The aim of the present study is to delve into such an effect by employing a well-defined form of chromium (Cr(III)-citrate) on the a) survival of pre- and mature adipocytes (3T3-L1), b) endogenous cell motility, and c) insulin-enhancing adipogenic capacity. The emerging results suggest that Cr(III)-citrate a) is (a)toxic in a concentration- and time-dependent manner, b) has no influence on cell motility, c) can induce 3T3-L1 pre-adipocyte differentiation into mature adipocytes through elevation of tissue specific biomarker levels (PPAR-γ, GLUT 4 and GCK), and d) exemplifies structurally-based metal-induced adipogenesis as a key process contributing to the development of future antidiabetic metallodrugs.
胰岛素抵抗可通过多种病理生理状况识别，如2型糖尿病、肥胖症、高血压及其他代谢综合征。增强胰岛素作用和/或用胰岛素增强剂或胰岛素模拟剂完全替代胰岛素似乎可改善代谢性疾病的治疗。在过去几十年中，深入研究一直致力于此类药物的研究，铬作为参与必要代谢化学过程的重要无机辅因子崭露头角。已表明三价铬通过增强胰岛素信号传导、作用以及胰岛素敏感组织的敏感性，在碳水化合物代谢中发挥核心作用。糖尿病与肥胖症之间极有可能的联系是脂肪组织，它以甘油三酯的形式储存能量并释放游离脂肪酸。迄今为止，关于铬对胰岛素激活的分子途径（如脂肪生成）影响的确切机制的信息匮乏。本研究的目的是通过使用一种明确形式的铬（柠檬酸铬（III））来深入探究这种影响，包括a）前脂肪细胞和成熟脂肪细胞（3T3-L1）的存活，b）内源性细胞运动，以及c）增强胰岛素的脂肪生成能力。新出现的结果表明，柠檬酸铬（III）a）在浓度和时间依赖性方式下具有（有）毒性，b）对细胞运动没有影响，c）可通过提高组织特异性生物标志物水平（PPAR-γ、GLUT 4和GCK）诱导3T3-L1前脂肪细胞分化为成熟脂肪细胞，并且d）例证了基于结构的金属诱导脂肪生成作为有助于未来抗糖尿病金属药物开发的关键过程。
