## 4 Discussion  
_Olea europaea_ leaves have been used to treat diabetes owing to their ability to decrease glucose, triglyceride, cholesterol, and LDL levels and increase high-density lipoprotein (HDL) levels. Many studies on the toxicity of OLE reported that it is generally safe for use even at high doses [34,35]. The purpose of this study was to explore the effect of OLE on glucose and lipid metabolism in diabetic rats. The mechanism involved in the management of hyperglycemia by OLE in diabetic animals has not been explored in previous studies [29,30,31,32]. Two concentrations of OLE (1% and 3%) were used to determine the protective effect on the animals in the present study. Although several drugs have been used for the treatment of diabetes, their high cost and adverse effects have resulted in the search for alternative therapies. Several types of herbs have been used to manage diabetes, and approximately 80% of people with diabetes are reported to depend on medicinal plants for successful treatment [33]. In agreement with the findings of previous studies, no significant effect of OLE or Met. was observed on the body weights of the rats in the present study [29,43]. Alternatively, significant increases in both FBS and PPS were observed in the D.W subgroups in groups 2 and 3 when compared with all the subgroups in G1 at the end of week 5, indicating the effect of STZ in these animals (Figure 1). Furthermore, the 1% OLE G3 subgroup presented with significantly higher levels of FBS and PPS than the other subgroups in G1, thus indicating that the low dose used (1% OLE) was not effective. A previous study showed that approximately 2-6 weeks of treatment with OLE were required to observe the desired effects [29,32,44]. The glucose levels in the 1% OLE G2 and 3% OLE G2 subgroups and the 3% OLE G3 subgroup were similar to G1; therefore, OLE might prove beneficial in reducing STZ toxicity, as reported previously [29,32,45]. Additionally, the STZ toxicity in the 1% OLE G2 subgroup was lower than that in the 1% OLE G3 subgroup, indicating that treatment with OLE before and after STZ injection might be more effective in preventing STZ toxicity and thereby preventing diabetes (Figure 1). The Met. subgroups in both groups 2 and 3 showed comparable results to those in the G1 subgroups, indicating the protective effect of Met. against diabetic hyperglycemia, as reported previously [43,46]. Moreover, decreased glucose levels were observed in the 1% OLE, 3% OLE, and Met. subgroups in G2 when compared with their negative controls (D.W-treated); similarly, decreased levels of FBS and PPS were observed in the  
Figure 7: Expression levels of GLUT4 in the groups at the end of week 5. G1: (control group), G2: received OLE and Met. 2 weeks before and 3 weeks after STZ injection, G3: received treatments with OLE and Met. 1 week after STZ injection for 2 weeks. Data are presented as mean \(\pm\) SD in 4–7 animals per subgroup. a.u, arbitrary units. 3% OLE G3 and Met. G3 subgroups when compared with their relative negative controls, statistical significance was notwithstanding. This may be explained by the increase in the duration and concentration required to lower the glucose levels, as reported in previous studies [29; 32; 47], which remained for 2-6 weeks when treated with OLE and may reach 6% OLE and 1-3 months when treated with Met. [43; 46]. A previous study showed that STZ can partially damage beta cells and induce T1D (type 1 diabetes (<50 mg/kg) or completely damage the beta cells in the pancreas leading to T1D (type 1 > 50 mg/kg), based on the dose used [37]. In the present study, the protective effect of 1% and 3% OLE against STZ toxicity was higher in G2 than in G3; 35% of the rats in G2 developed diabetes compared with 57% in G3. This difference in response to STZ toxicity may be attributed to the OLE treatment provided to the G2 rats before STZ injection. The insulin levels in the 1% and 3% OLE G2 subgroups were similar to those in the 3% OLE and Met.