多潘立酮对胰岛素分泌的影响及相关机制
发布时间：2019-02-16 22:32
【摘要】：目的:已有研究报道多巴胺在中枢和外周多个层面发挥对糖代谢的调控作用。胰岛β细胞自身可以合成多巴胺,多巴胺和多巴胺D2受体激动剂对胰岛有抑制胰岛素分泌的作用。多潘立酮(DPD)作为经典的多巴胺D2受体拮抗剂,在临床上应用较为广泛。因为它有明确的促进胃动力和止吐作用,故而经常被用来治疗糖尿病胃病。有少数研究(临床试验和动物实验)阐述了应用多潘立酮对胰岛素分泌的影响,然而研究结论并不统一。所以本实验室就多潘立酮对胰岛素分泌的影响进行了在体和离体实验,并且尝试研究了相关的作用机制,为多潘立酮的临床应用提供更多依据,并在多巴胺和能量代谢系统关系的研究领域增加新的证据。方法:1.给c57小鼠腹腔注射多潘立酮溶液,测定其对腹腔注射葡萄糖耐量(IPGTT)及同步胰岛素释放的影响。2.处死小鼠后,迅速打开小鼠腹腔,将小肠拨至一侧,暴露并剥离一段胆管,找到胆总管与十二指肠交汇处,以止血钳夹闭壶腹部乳头区,将配置好的胶原酶Ⅴ从剥离好的一段胆总管打入胰腺,小心剥离胰腺,38℃水浴震荡消化16 min,手工挑取小鼠胰岛。用Dispase II消化得到小鼠胰岛β细胞。3.将分得的胰岛培养过夜后,用放射性免疫分析法检测多潘立酮干预对小鼠胰岛素分泌的影响。4.采用钙离子成像技术检测多潘立酮对胰岛β细胞内钙离子浓度的影响。5.胰岛培养过夜后,用ELISA分析法检测多潘立酮干预对细胞内环磷酸腺甘(c AMP)含量的影响。结果:1.单次腹腔注射(IP)多潘立酮(DPD 5mg/Kg)或DMSO溶剂后检测IPGTT中血糖和血浆胰岛素浓度,结果提示多潘立酮增强了葡萄糖刺激的胰岛素释放,并且在30分钟时浓度较对照组显著升高(n=6 P0.05)。多潘立酮组血糖值在多个时点(5-60分)较对照组有升高趋势,但无统计学差异。2.在离体胰岛素分泌实验中,高糖(16.7m M)时多潘立酮对分离的胰岛有促胰岛素分泌作用,并且其促分泌作用随着药物浓度的增加而呈现逐渐加强趋势。低糖(2.8m M)时多潘立酮没有促胰岛素分泌作用。因而,在除外在体实验中其他机制参与的情况下,该实验证实了即刻作用后多潘立酮可以增强葡萄糖刺激的胰岛素分泌(GSIS)。3.钙离子成像技术显示,在16.7m M葡萄糖的基础上,多潘立酮可进一步升高β细胞内的钙离子浓度和钙离子振荡频率。4.在高糖环境下(16.7m M)孵育小鼠胰岛,较溶剂对照组,多潘立酮可显著增加胰岛β细胞内的c AMP含量,高糖+溶剂对照组(n=12)vs高糖+50μmol/L DPD组(n=12),P0.05。结论:1.腹腔注射多潘立酮促进了c57小鼠IPGTT 30分钟时点的胰岛素分泌。2.在离体实验中,多潘立酮对c57小鼠胰岛具有葡萄糖依赖性的促胰岛素分泌作用。3.多潘立酮通过增加β细胞内钙离子浓度促进胰岛素分泌。4.多潘立酮增加了β细胞内c AMP浓度,可能参与了促胰岛素分泌机制。
[Abstract]:Aim: dopamine has been reported to regulate glucose metabolism at central and peripheral levels. Islet 尾 cells can synthesize dopamine, dopamine and dopamine D2 receptor agonists to inhibit insulin secretion. As a classic dopamine D 2 receptor antagonist, domperidone (DPD) is widely used in clinic. It is often used to treat diabetic gastropathy because it promotes gastric motility and stops vomiting. A few studies (clinical and animal) have described the effects of domperidone on insulin secretion, but the findings are not uniform. So we have carried out both in vivo and in vitro experiments on the effect of domperidone on insulin secretion, and have tried to study the related mechanism, which provides more evidence for the clinical application of domperidone. New evidence has also been added to the field of research on the relationship between dopamine and energy metabolism systems. Methods: 1. The effects of domperidone solution on glucose tolerance (IPGTT) and simultaneous insulin release were measured in c 57 mice. After the mice were killed, the abdominal cavity of the mice was quickly opened, the small intestine was moved to one side, a segment of the bile duct was exposed and stripped, and the junction of the common bile duct and the duodenum was found, so that the papilla area of the ampulla could be closed by the hemostatic forceps. The configured collagenase 鈪，
本文编号：2424906
[Abstract]:Aim: dopamine has been reported to regulate glucose metabolism at central and peripheral levels. Islet 尾 cells can synthesize dopamine, dopamine and dopamine D2 receptor agonists to inhibit insulin secretion. As a classic dopamine D 2 receptor antagonist, domperidone (DPD) is widely used in clinic. It is often used to treat diabetic gastropathy because it promotes gastric motility and stops vomiting. A few studies (clinical and animal) have described the effects of domperidone on insulin secretion, but the findings are not uniform. So we have carried out both in vivo and in vitro experiments on the effect of domperidone on insulin secretion, and have tried to study the related mechanism, which provides more evidence for the clinical application of domperidone. New evidence has also been added to the field of research on the relationship between dopamine and energy metabolism systems. Methods: 1. The effects of domperidone solution on glucose tolerance (IPGTT) and simultaneous insulin release were measured in c 57 mice. After the mice were killed, the abdominal cavity of the mice was quickly opened, the small intestine was moved to one side, a segment of the bile duct was exposed and stripped, and the junction of the common bile duct and the duodenum was found, so that the papilla area of the ampulla could be closed by the hemostatic forceps. The configured collagenase 鈪，
本文编号：2424906
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