Citrus sinensis (L.) Osbeck is extensively cultivated worldwide and one of the most consumed fruits in the world. We evaluated the therapeutic properties of the methanol extract from Citrus sinensis fruit peel (CSMe) in high-fat diet-fed streptozotocin-induced insulin-resistant diabetic rats. Body weight, food intake, and water consumption were analysed. Biochemical and molecular biologic indices, and the expression of insulin receptor-induced signalling molecules were assessed to identify possible mechanisms. In addition, we conducted histology of pancreatic and adipose tissues. UHPLC-MS/MS analysis showed the presence of 17 dietary phenolics at substantial concentrations. High-fat diet-fed streptozotocin-induced diabetic rats administered CSMe (50 and 100 mg/kg) had reduced fasting blood glucose (56.1% and 55.7%, respectively) and plasma insulin levels (22.9% and 32.7%, respectively) compared with untreated diabetic control rats. CSMe reversed the biochemical abnormalities in diabetic rats, showed cytoprotective activity, and increased the intensity of the positive immunoreactions for insulin in pancreatic islets. CSMe treatment increased the expression of PPARγ in the adipose tissue and signalling molecules GLUT4 and insulin receptor. Our data suggest that CSMe could optimize glucose uptake of adipose tissues through the insulin-dependent signalling cascade mechanism and it should be investigated in the management of individuals with type 2 diabetes mellitus.

柑桔（O.beck）在世界范围内广泛种植，是世界上消费最多的水果之一。我们评估了柑桔中甲醇提取物的治疗特性高脂饮食喂养的链脲佐菌素诱导的胰岛素抵抗糖尿病大鼠体内的果皮（CSMe）。分析了体重，食物摄入量和水消耗量。评估了生化和分子生物学指标，以及胰岛素受体诱导的信号分子的表达，以确定可能的机制。此外，我们进行了胰腺和脂肪组织的组织学检查。UHPLC-MS / MS分析显示，有17种高浓度膳食酚存在。高脂饮食喂养的链脲佐菌素诱导的糖尿病大鼠服用CSMe（50和100 mg / kg）的空腹血糖（分别为56.1％和55.7％）和血浆胰岛素水平（分别为22.9％和32.7％）降低。未经治疗的糖尿病对照大鼠。CSMe逆转了糖尿病大鼠的生化异常，显示出细胞保护活性，并增加了胰岛中胰岛素阳性免疫反应的强度。CSMe处理可增加脂肪组织和信号分子GLUT4和胰岛素受体中PPARγ的表达。我们的数据表明CSMe可以通过胰岛素依赖性信号传导级联机制优化脂肪组织的葡萄糖摄取，应在2型糖尿病患者的治疗中进行研究。