Department of Endocrinology and Metabolism, Shenzhen People's Hospital (Second Clinical Medical Collage of Jinan University), Shenzhen, Guangdong, China.
Department of Endocrinology, Qingdao Municipal Hospital, Qingdao, Shandong, China.
J Biochem Mol Toxicol. 2021 Jun;35(6):1-12. doi: 10.1002/jbt.22763. Epub 2021 Mar 16.
The current study was done to measure the role of piperlongumine (PL) on hyperglycemia interrelated oxidative stress-mediated inflammation and apoptosis, inflammatory stress, and the diabetic insulin receptor substrate 2 (IRS2), protein kinase B (AKT), and glucose transporter 2 (GLUT-2)/4 signaling pathway in streptozotocin (STZ)-persuaded diabetic animals. Diabetes was initiated in experimental animals via a single dose intraperitoneal inoculation of STZ. Diabetic rats revealed an augmented blood-glucose level with drastically diminished plasma-insulin status. The functions of antioxidants were diminished with enhanced lipid peroxidation, conjugated dienes, and protein carbonyls noticed in diabetic rats' plasma and pancreatic tissues. An elevation of nuclear factor-κB (NF-κB), tumor necrosis factor-α, and interleukin-6 proteins was noticed in pancreatic tissues as well as IRS2, AKT, GLUT-2, and GLUT-4 marker expressions were quantified in the hepatic tissue of control and diabetic rats. Oral administration of PL for 30 days drastically lowered glucose and higher insulin status in STZ-induced diabetic rats. Impressively, PL oral supplementation considerably restored the antioxidant levels and reduced inflammation and diabetic marker expressions in STZ-diabetic rats. These results were supported through a histological study. Moreover, PL also augmented the level of B-cell lymphoma 2 and diminished the level of Bcl-2-associated X protein in STZ-treated rat's hepatic tissues. Thus, we concluded that PL excellently rescued pancreatic β cells through mitigating hyperglycemia via dynamic insulin secretion, activating antioxidants, and inhibiting inflammation and apoptosis in the pancreatic and hepatic tissue of diabetic rats.
本研究旨在测量胡椒碱（PL）在高血糖相关氧化应激介导的炎症和细胞凋亡、炎症应激以及糖尿病胰岛素受体底物 2（IRS2）、蛋白激酶 B（AKT）和葡萄糖转运体 2（GLUT-2/4）信号通路中的作用，在链脲佐菌素（STZ）诱导的糖尿病动物中。通过单次腹腔内接种 STZ 启动实验动物的糖尿病。糖尿病大鼠的血糖水平升高，血浆胰岛素水平显著降低。糖尿病大鼠的血浆和胰腺组织中抗氧化剂的功能降低，脂质过氧化、共轭二烯和蛋白质羰基增加。还观察到胰腺组织中核因子-κB（NF-κB）、肿瘤坏死因子-α和白细胞介素-6 蛋白的升高，以及控制和糖尿病大鼠肝组织中 IRS2、AKT、GLUT-2 和 GLUT-4 标志物的表达。PL 口服给药 30 天可显著降低 STZ 诱导的糖尿病大鼠的血糖和升高胰岛素水平。令人印象深刻的是，PL 口服补充剂可显著恢复抗氧化剂水平，并降低 STZ 糖尿病大鼠的炎症和糖尿病标志物表达。这些结果通过组织学研究得到支持。此外，PL 还增加了 B 细胞淋巴瘤 2 的水平，并降低了 STZ 处理大鼠肝组织中 Bcl-2 相关 X 蛋白的水平。因此，我们得出结论，PL 通过动态胰岛素分泌减轻高血糖，激活抗氧化剂，抑制糖尿病大鼠胰腺和肝组织中的炎症和细胞凋亡，极好地挽救了胰腺 β 细胞。
