## 3 Discussion
When ROS exceeds the capability of this antioxidant system, which is the case in diabetes, it will stimulate oxidative stress and lead to cell apoptosis and dysfunction [35, 36]. To date, the application of antioxidants is still an important approach to protect the survival and function of \(\beta\)-cells [5, 37]. In our previous paper, we showed that SOE has a potent antioxidant activity in radical-scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2\({}^{\prime}\)-azino-bis(3-ethylbenzothazoline-6-sulphonic acid) (ABTS), and we showed that it is a good antioxidant [25]. Indeed, we showed in this study that HG stimulated the production of ROS and that SOE treatment could greatly attenuate the ROS generation to the normal level (Figure 2). When the expression level of antioxidant enzymes such as catalase (an abundant peroxidase), GPx (a peroxide decomposition enzyme), and SOD (a defense enzyme and scavenger of free radicals) is low in pancreatic islets, pancreatic \(\beta\)-cells are easily damaged by mitochondrial ROS [33, 38]. The enhancement of the activity of catalase, GPx, and SOD can reduce the production of ROS in cells and protect \(\beta\)-cells and islets from oxidative damage [16, 39, 40, 41]. GSH is a biological antioxidant that can neutralize ROS and prevent the cell damage caused by free radicals, peroxides, lipid peroxides, and heavy metals. The administration of GSH to SD rats could block the glucose/ROS-induced \(\beta\)-cell damages [42]. The present study indicates that the treatment of SOE to HG-stimulated pancreatic \(\beta\)-cells could increase catalase, GPx, and SOD activities and the intracellular GSH level (Figure 3). Since the protein expression of these antioxidant enzymes were significantly increased after SOE treatment, we conclude that the elevation of the antioxidant enzyme activities was mainly due to the increase in the expression of these enzyme proteins (Figure 4). When the blood glucose level rises, pancreatic \(\beta\)-cells would secrete insulin to maintain glucose homeostasis. However, chronic hyperglycemia induced-glucotoxicity may cause death and function loss of \(\beta\)-cell, thereby blocking the production of insulin [36]. This study shows that secretion of insulin in RIN-m5f \(\beta\)-cells incubated for 24 h with glucose at a lower concentration (50 mM) was significantly induced but reduced when treated with a higher concentration of glucose (100 mM). It is worth noting that even though the cell growth, the production of ROS and GSH, and the antioxidant enzyme activity in \(\beta\)-cells were affected when cultured under 50 mM glucose, the insulin secretion function was still maintained at a normal elevated state. This could be due to the fact that pancreatic \(\beta\)-cells need more time to regulate the insulin secretion function [33], and the HG treatment time in this study was only 24 h. However, when the glucose concentration was increased to 100 mM, the insulin secretion of \(\beta\)-cells could no longer be maintained at a normal level. In this study, we show that SOE can adjust the insulin secretion by \(\beta\)-cells. In cells cultured in 50 mM glucose condition, SOE can reduce insulin secretion to the normal level, while under the 100 mM glucose condition, SOE can adjust the insulin secretion upward to return to the normal level (Figure 5). Therefore, SOE has a two-way regulation effect on insulin secretion of the HG-treated \(\beta\)-cells. The toxic effect of SOE on cancer cells was caused by inducing apoptosis of cancer cells [23]; however, this study found that SOE has a protective effect on the survival of \(\beta\)-cells in the HG environment. This phenomenon should be due to the antioxidant effect of SOE alleviating the oxidative stress caused by HG, thereby reducing the cell apoptosis caused by oxidative stress and maintain the normal secretion of insulin.