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

Oncotarget
Jimin KimJae Wha Kim

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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Citations

Aug 18, 2020·Bioscience, Biotechnology, and Biochemistry·Haohui LiangPing Zhou
Oct 26, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hye Young KimDae Won Jun
Oct 31, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Dinesh Kumar ChellappanKamal Dua

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Methods Mentioned

BETA
nuclear translocation
flow cytometry
Fluorescence
ELISA

Software Mentioned

ImageJ

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis