ABSTRACT

The endocannabinoid system is found in tissues that regulate the glycemia, including adipose tissue, muscle, and pancreatic islets. Diet-induced metabolic syndrome changes the expression of the CB receptors in muscle, adipose tissue, and liver. However, it is poorly understood whether metabolic syndrome (MetS) affects the expression of CB receptors in pancreatic β cells. We analyzed the expression of CB receptors in pancreatic β cells under chronic high-sucrose diet (HSD)-induced MetS. Wistar rats fed an HSD as a model of MetS were used to investigate changes in cannabinoid receptors. After 8 weeks of treatment, we evaluated the appearance of the following MetS biomarkers: glucose intolerance, hyperinsulinemia, insulin resistance, hypertriglyceridemia, and an increase in visceral adiposity. To determine the presence of CB1 and CB2 receptors in pancreatic β cells, immunofluorescence of primary cell cultures and pancreatic sections was performed. For whole-islet quantification of membrane-bound CB1 and CB2 receptors, western-blotting following differential centrifugation was conducted. Our results revealed that an HSD treatment closely mimics the alterations seen in MetS. We observed that in primary cell culture, CB1 and CB2 receptors were expressed at a higher level in pancreatic β cells compared with non-β cells. MetS resulted in a reduction of CB1 in the islet, whereas abundant CB2 was observed after the treatment. CB1 and CB2 receptors are differentially expressed in pancreatic β cells during MetS development.

摘要

内源性大麻素系统存在于调节血糖的组织中，包括脂肪组织，肌肉和胰岛。饮食引起的代谢综合征改变了肌肉，脂肪组织和肝脏中CB受体的表达。然而，人们对代谢综合症（MetS）是否影响胰腺β细胞中CB受体的表达了解甚少。我们分析了慢性高蔗糖饮食（HSD）诱导的MetS在胰腺β细胞中CB受体的表达。将以HSD作为MetS模型的Wistar大鼠用于研究大麻素受体的变化。治疗8周后，我们评估了以下MetS生物标志物的出现：葡萄糖耐量，高胰岛素血症，胰岛素抵抗，高甘油三酸酯血症和内脏脂肪增多。为了确定胰腺β细胞中CB1和CB2受体的存在，对原代细胞培养物和胰腺切片进行了免疫荧光分析。为了对膜结合的CB1和CB2受体进行全胰岛定量，在进行了差速离心后进行了Western blotting。我们的结果表明，HSD治疗与MetS中观察到的变化密切相似。我们观察到，在原代细胞培养中，与非β细胞相比，胰腺β细胞中CB1和CB2受体的表达水平更高。MetS导致胰岛中CB1减少，而在治疗后观察到大量CB2。在MetS发育过程中，CB1和CB2受体在胰腺β细胞中差异表达。为了对膜结合的CB1和CB2受体进行全胰岛定量，在进行了差速离心后进行了Western blotting。我们的结果表明，HSD治疗与MetS中观察到的变化密切相似。我们观察到，在原代细胞培养中，与非β细胞相比，胰腺β细胞中CB1和CB2受体的表达水平更高。MetS导致胰岛中CB1减少，而在治疗后观察到大量CB2。在MetS发育过程中，CB1和CB2受体在胰腺β细胞中差异表达。为了对膜结合的CB1和CB2受体进行全胰岛定量，在进行了差速离心后进行了Western blotting。我们的结果表明，HSD治疗与MetS中观察到的变化密切相似。我们观察到，在原代细胞培养中，与非β细胞相比，胰腺β细胞中CB1和CB2受体的表达水平更高。MetS导致胰岛中CB1减少，而在治疗后观察到大量CB2。在MetS发育过程中，CB1和CB2受体在胰腺β细胞中差异表达。与非β细胞相比，CB1和CB2受体在胰腺β细胞中的表达水平更高。MetS导致胰岛中CB1减少，而在治疗后观察到大量CB2。在MetS发育过程中，CB1和CB2受体在胰腺β细胞中差异表达。与非β细胞相比，CB1和CB2受体在胰腺β细胞中的表达水平更高。MetS导致胰岛中CB1减少，而在治疗后观察到大量CB2。在MetS发育过程中，CB1和CB2受体在胰腺β细胞中差异表达。