Laboratory of Regenerative Pharmacology, Goldberg ED Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Centre of the Russian Academy of Sciences, Lenin, 3, 634028 Tomsk, Russia.
Obschestvo s ogranichennoi otvetstvennostiyu "PHARMENTERPRISES", 143026 Moscow, Russia.
Int J Mol Sci. 2020 Feb 3;21(3):991. doi: 10.3390/ijms21030991.
In clinical practice, the metabolic syndrome can lead to multiple complications, including diabetes. It remains unclear which component of the metabolic syndrome (obesity, inflammation, hyperglycemia, or insulin resistance) has the strongest inhibitory effect on stem cells involved in beta cell regeneration. This makes it challenging to develop effective treatment options for complications such as diabetes. In our study, experiments were performed on male C57BL/6 mice where metabolic disorders have been introduced experimentally by a combination of streptozotocin-treatment and a high-fat diet. We evaluated the biological effects of Bisamide Derivative of Dicarboxylic Acid (BDDA) and its impact on pancreatic stem cells in vivo. To assess the impact of BDDA, we applied a combination of histological and biochemical methods along with a cytometric analysis of stem cell and progenitor cell markers. We show that in mice with metabolic disorders, BDDA has a positive effect on lipid and glucose metabolism. The pancreatic restoration was associated with a decrease of the inhibitory effects of inflammation and obesity factors on pancreatic stem cells. Our data shows that BDDA increases the number of pancreatic stem cells. Thus, BDDA could be used as a new compound for treating complication of the metabolic syndrome such as diabetes.
在临床实践中,代谢综合征会导致多种并发症,包括糖尿病。目前尚不清楚代谢综合征的哪个组成部分(肥胖、炎症、高血糖或胰岛素抵抗)对参与β细胞再生的干细胞具有最强的抑制作用。这使得开发针对糖尿病等并发症的有效治疗方法变得具有挑战性。在我们的研究中,对雄性 C57BL/6 小鼠进行了实验,这些小鼠通过链脲佐菌素处理和高脂肪饮食的组合实验性地产生了代谢紊乱。我们评估了双酰胺二羧酸衍生物(BDDA)的生物学效应及其对体内胰腺干细胞的影响。为了评估 BDDA 的影响,我们应用了组织学和生化方法以及对干细胞和祖细胞标志物的细胞计量分析相结合的方法。我们表明,在患有代谢紊乱的小鼠中,BDDA 对脂质和葡萄糖代谢有积极影响。胰腺的恢复与炎症和肥胖因素对胰腺干细胞的抑制作用的降低有关。我们的数据表明,BDDA 增加了胰腺干细胞的数量。因此,BDDA 可以用作治疗代谢综合征的并发症(如糖尿病)的新型化合物。