Chinese Medicine FTZ Recipe Protects against High-Glucose-Induced Beta Cell Injury through Alleviating Oxidative Stress.

Weijian Bei,Zhanhui Gu,Jianmei Chen,Jiao Guo,Yijian Huang,Yinming Hu,Wei Xu,Jinyan Cai,Lexun Wang,Jingjing Zhang,Yujiao Wang,Zili Lei

doi:10.1155/2019/6378786

Abstract

Objective To investigate the effect of FTZ on high-glucose-induced oxidative stress and underlying mechanisms. Methods We used a β cell dysfunction and diabetes model that was induced in rats fed a high-fat high-sugar diet (HFHSD) for 6 weeks and injected once with 35 mg/kg streptozocin (STZ). Then, 3 and 6 g/kg of FTZ were administered by gavage for 8 weeks. In addition, an ex vivo model of oxidative stress was induced by stimulating INS-1 cells with 25 mmol/L glucose for 48 h. Result The levels of fasting blood glucose (FBG) in diabetic model rats were obviously higher than those in the normal group; furthermore with reduced levels of β cells, catalase (CAT), superoxide dismutase (SOD), and Bcl-2 increased lipid peroxide malondialdehyde (MDA) and caspase-3 in the pancreatic tissue of the diabetic model rats. Afterward, the cells were incubated with FTZ-containing serum and edaravone. The 25 mmol/L glucose-induced SOD reduction increased MDA and intracellular ROS. The protein expression level of Mn-SOD and CAT in the model group decreased significantly compared with that in the control group. Conclusion FTZ treatment significantly improved the alteration in the level of SOD, CAT, Bcl-2, caspase-3, and MDA coupled with β cell dysfunction in diabetic rats. Oxidative stress in INS-1 cells was closely associated with a higher rate of apoptosis, increased production of ROS and MDA, enhanced Bax expression, and caspase-3, -9 activities and markedly decreased protein expression of Mn-SOD and CAT. FTZ-containing serum incubation notably reversed the high-glucose-evoked increase in cell apoptosis, production of ROS and MDA, and Bax protein levels. Furthermore, FTZ stimulation upregulated the expression levels of several genes, including Mn-SOD, CAT, and Bcl-2/Bcl-xl. In addition, FTZ decreased the intracellular activity of caspase-3, -9 in INS-1 cells. FTZ protected β-cells from oxidative stress induced by high glucose in vivo and in vitro. The beneficial effect of FTZ was closely associated with a decrease in the activity of caspase-3, -9 and intracellular production of ROS, MDA, and Bax coupled with an increase in the expression of Mn-SOD, CAT, and Bcl-2/Bcl-xl.

Highlights

Type 2 diabetes, a chronic metabolic noncommunicable disease characterized by high blood glucose, with pathologic insulin resistance and subsequent β-cell dysfunction, has become a serious hazard to human health [1, 2]
We demonstrated that Fufang Zhenshu Tiao-Zhi (FTZ) protected pancreatic β cells from damage from exposure to high concentrations of glucose by reducing reactive oxygen species (ROS) and MDA and increasing Mn-superoxide dismutase (SOD) and CAT
Diabetes with significantly higher levels of blood glucose was induced in healthy adult SD male rats by feeding a high-fat high-sugar diet (HFHSD) for 6 weeks and by intraperitoneal injection with 35 mg/kg STZ

Summary

Introduction

Type 2 diabetes, a chronic metabolic noncommunicable disease characterized by high blood glucose, with pathologic insulin resistance and subsequent β-cell dysfunction, has become a serious hazard to human health [1, 2]. Oxidative stress resulting from exposure to high level glucose is considered to be one of the key factors of β-cell dysfunction in type 2 diabetes and the basis of diabetic complications [3,4,5,6,7,8,9,10]. Under constantly high blood glucose levels, superoxide products will increase greatly, and oxidative stress will be generated when the production rate of the superoxide products exceeds the removal rate [6,7,8]. Oxidative stress and ROS cause islet β cell damage through the NF-κB pathway [15, 16], which prompts follow-up apoptosis signaling cascade amplification, leading to cell apoptosis [17, 18]

Results

Discussion

Conclusion