HX-1171 attenuates pancreatic β-cell apoptosis and hyperglycemia-mediated oxidative stress via Nrf2 activation in streptozotocin-induced diabetic model

Abstract

Streptozotocin (STZ) acts specifically on pancreatic beta cells, inducing cell destruction and cell dysfunction, resulting in diabetes. Many studies have reported that nuclear factor-erythroid 2-related factor 2 (Nrf2), a main regulator of antioxidant expression, prevents and improves diabetes-related diseases. In this study, we investigated the antidiabetic effect of the newly discovered Nrf2 activator, HX-1171, in the STZ-induced diabetic mouse model. HX-1171 enhanced insulin secretion by reducing STZ-induced cell apoptosis, and decreased intracellular reactive oxygen species (ROS) generation by upregulating the expression of antioxidant enzymes through Nrf2 activation in INS-1 pancreatic beta cells. In STZ-induced diabetic mice, HX-1171 administration significantly lowered blood glucose levels and restored blood insulin levels. In the STZ-only injected mice, the pancreatic islets showed morphological changes and loss of function, whereas the HX-1171-treated group was similar to that of the control group. These results suggest that HX-1171 may be developed as a promising therapeutic agent for diabetes-related diseases.

Hypoglycemic effect of a novel polysaccharide fromLentinus edodeson STZ-induced diabetic miceviametabolomics study and Nrf2/HO-1 pathway

“…The tissue sections were visualized under a light microscope (Leica DM750). 25,26 2.6 Ultra performance liquid chromatography-quadrupoletime-of-flight/mass spectrometer (UPLC-Q-TOF/MS) analysis Sample preparation and detection were performed according to the study described by Gao et al with slight modifications. 27 In brief, 100 μL of mouse serum samples was added and mixed with acetonitrile (v : v = 1 : 4), centrifuged, and the supernatant was freeze-dried.…”

Propionate ameliorates diabetes-induced neurological dysfunction through regulating the PI3K/Akt/eNOS signaling pathway

“…Its activity in inducing diabetes may be through free radical damage to islet β-cells, which impairs the insulin-producing function of islet β-cells and leads to diabetes. Intraperitoneal injection of STZ has recently been applied in many diabetes-related studies to specifically destroy pancreatic β-cells, resulting in secretion disorder and persistent hyperglycemia without toxicity to brain cells [42] . In this study, after a single intraperitoneal injection of STZ at 55 mg/kg to mice, their body weight was significantly decreased, and the fasting blood glucose level could reach up to or more than 20 mmol/L.…”

Therapeutic Cell Protective Role of Histochrome under Oxidative Stress in Human Cardiac Progenitor Cells

“…To determine cell cytotoxicity, hCPCs were seeded at 5000 cells/well in a 96-well plate. The following day, cells were pretreated with different concentrations of histochrome and incubated for 24 h. Cell viability was evaluated using a cell-counting kit (CCK) cell viability assay kit (#CCK-3000, DonginLS, Seoul, Republic of Korea), following the manufacturer’s instructions [48,49]. The cell viability was measured by incubating cells with the CCK solution.…”