Piperlongumine attenuates oxidative stress, inflammatory, and apoptosis through modulating the GLUT-2/4 and AKT signaling pathway in streptozotocin-induced diabetic rats

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-kappa B (NF-kappa B), tumor necrosis factor-alpha, 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 beta cells through mitigating hyperglycemia via dynamic insulin secretion, activating antioxidants, and inhibiting inflammation and apoptosis in the pancreatic and hepatic tissue of diabetic rats.