Department of Chemical Engineering, Faculty of Engineering and Science, Curtin University, CDT 250, 98009, Miri, Sarawak, Malaysia.
Chemical Engineering Department, University of Tennessee, Chattanooga, TN, 37403, USA.
Appl Biochem Biotechnol. 2020 Apr;190(4):1385-1410. doi: 10.1007/s12010-019-03166-z. Epub 2019 Nov 27.
Insulin resistance is one of the major factors that leads to type 2 diabetes. Although insulin therapies have been shown to overcome insulin resistance, overweight and hypoglycemia are still observed in most cases. The disadvantages of insulin therapies have driven the interest in developing novel curative agents with enhanced insulin resistance reversibility. Magnesium deficiency has also been recognized as a common problem which leads to insulin resistance in both type 1 and 2 diabetes. Oxide nanoparticles demonstrate highly tunable physicochemical properties that can be exploited by engineers to develop unique oxide nanoparticles for tailored applications. Magnesium supplements for diabetic cells have been reported to increase the insulin resistance reversibility. Hence, it is hypothesized that magnesium oxide (MgO) nanoparticles could be molecularly engineered to offer enhanced therapeutic efficacy in reversing insulin resistance. In the present work, morphologically different MgO nanoparticles were synthesized and evaluated for biophysical characteristics, biocompatibility, cytotoxicity, and insulin resistance reversibility. MTT assay revealed that hexagonally shaped MgO nanoparticles are less toxic to 3T3-L1 adipose cells (diabetic) compared with spherically and rod-shaped MgO nanoparticles. MTT assays using VERO cells (normal, non-diabetic) showed that 400 μg/ml of hexagonal MgO nanoparticles were less toxic to both diabetic and non-diabetic cells. DNS glucose assay and western blot showed that hexagonally shaped MgO nanoparticles had reversed 29.5% of insulin resistance whilst fluorescence microscopy studies indicated that the insulin resistance reversal is due to the activation of intracellular enzymes. The probable mechanism for MgO nanoparticles to induce cytotoxic effect and insulin resistance reversal is discussed.
胰岛素抵抗是导致 2 型糖尿病的主要因素之一。尽管胰岛素治疗已被证明可以克服胰岛素抵抗，但在大多数情况下仍会出现超重和低血糖。胰岛素治疗的缺点促使人们对开发具有增强胰岛素抵抗逆转能力的新型治疗药物产生了兴趣。镁缺乏也已被认为是导致 1 型和 2 型糖尿病胰岛素抵抗的常见问题。氧化物纳米粒子表现出高度可调的物理化学性质，工程师可以利用这些性质来开发用于特定应用的独特氧化物纳米粒子。据报道，糖尿病细胞的镁补充剂可以增加胰岛素抵抗的逆转性。因此，假设氧化镁（MgO）纳米粒子可以进行分子工程设计，以提供增强的治疗效果，从而逆转胰岛素抵抗。在本工作中，合成了形态不同的 MgO 纳米粒子，并对其进行了生物物理特性、生物相容性、细胞毒性和胰岛素抵抗逆转性的评价。MTT 分析表明，六方形状的 MgO 纳米粒子对 3T3-L1 脂肪细胞（糖尿病）的毒性小于球形和棒形 MgO 纳米粒子。用 VERO 细胞（正常，非糖尿病）进行的 MTT 分析表明，400μg/ml 的六方 MgO 纳米粒子对糖尿病和非糖尿病细胞的毒性都较小。DNS 葡萄糖测定和 Western blot 表明，六方形状的 MgO 纳米粒子逆转了 29.5%的胰岛素抵抗，而荧光显微镜研究表明，胰岛素抵抗的逆转是由于细胞内酶的激活。讨论了 MgO 纳米粒子诱导细胞毒性和胰岛素抵抗逆转的可能机制。
