Oncotarget

Research Papers:

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

Jimin Kim _, Su-Hyun Shin, Jong-Koo Kang and Jae Wha Kim

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Oncotarget. 2018; 9:24260-24271. https://doi.org/10.18632/oncotarget.24916

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Abstract

Jimin Kim1,2, Su-Hyun Shin1,2, Jong-Koo Kang3 and Jae Wha Kim1,2

1Cell Factory Research Center, Division of Systems Biology and Bioengineering, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea

2Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, Daejeon, Republic of Korea

3Department 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.


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