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

// Jimin Kim 1, 2 , Su-Hyun Shin 1, 2 , Jong-Koo Kang 3 and Jae Wha Kim 1, 2 1 Cell Factory Research Center, Division of Systems Biology and Bioengineering, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea 2 Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, Daejeon, Republic of Korea 3 Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea Correspondence to: Jae Wha Kim, email: wjkim@kribb.re.kr Keywords: HX-1171; Nrf2 activator; beta cell; diabetes; hyperglycemia Received: July 17, 2017 Accepted: September 04, 2017 Epub: March 23, 2018 Published: May 11, 2018 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.