中华医学杂志（英文版）2010，Vol.123Issue(24)：3652-3657,6.DOI:10.3760/cma.j.issn.0366-6999.2010.24.026
RNA interference targeting mu-opioid receptors reverses the inhibition of fentanyl on glucose-evoked insulin release of rat islets
RNA interference targeting mu-opioid receptors reverses the inhibition of fentanyl on glucose-evoked insulin release of rat islets
QIAN Tao-lai 1ZHANG Lei 2WANG Xin-hua 3LIU Sheng 4MA Liang 5LU Ying6
作者信息
- 1. Department of Anesthesiology, Shenzhen Shekou People's Hospital, Shenzhen, Guangdong 518067, China
- 2. Pain Management Department, Shanghai Dongfang Hospital, Tongji University, Shanghai 200120, China
- 3. Department of Anesthesiology, Shanghai Dongfang Hospital, Tongji University, Shanghai 200120, China
- 4. Cell Therapy Center, Shanghai Dongfang Hospital, Tongji University, Shanghai 200120, China
- 5. Central Laboratory, Shanghai Dongfang Hospital, Tongji University, Shanghai 200120, China
- 折叠
摘要
Abstract
Background Mu opioid receptor plays an important role in many physiological functions. Fentanyl is a widely used opioid receptor agonist for analgesia. This study was conducted to test the role of mu-opioid receptor on insulin release by determining whether fentanyl affected insulin release from freshly isolated rat pancreatic islets and if small interfering RNAs (siRNA) targeting mu-opioid receptor in the islets could knock down mu-opioid receptor expression.Methods Islets were isolated from ripe SD rats' pancreas by common bile duct intraductal collagenase V digestion and purified by discontinuous Ficoll density gradient centrifugation. The siRNA knock-down of mu-opioid receptor mRNA and protein in islet cells was analyzed by semi-quantitative real time-PCR and Western blotting. After siRNA-transfection for 48 hours, the islets were co-cultured with fentanyl as follows: 0 ng/ml, 3 ng/ml and 30 ng/ml for 48 hours. Then glucose-evoked insulin release was performed. As a control, the insulin release was also analyzed in islets without siRNA-trasfection after being co-cultured with fentanyl for 48 hours.Results After 48 hours of transfections, specific siRNA targeting of mu-opioid receptors produced significant reduction of mu-opioid receptor mRNA and protein (P ＜0.01). Fentanyl significantly inhibited glucose-evoked insulin release in islets in a concentration dependent manner (P ＜0.01). But after siRNA-transfection for 48 hours, the inhibition on glucose-evoked insulin reiease was reversed (P ＜0.01).Conclusions RNA interference specifically reduces mu-opioid receptor mRNA and protein expression, leading to reversal of the fentanyl-induced inhibition on glucose-evoked insulin release of rat islets. The activation of opioid receptor induced by fentanyl functions to inhibit insulin release. The use of RNAi presents a promising tool for future research in diabetic mechanisms and a novel therapy for diabetes.关键词
RNA interference/mu-opioid receptor/fentanyl/inhibition/insulin releaseKey words
RNA interference/mu-opioid receptor/fentanyl/inhibition/insulin release分类
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QIAN Tao-lai,ZHANG Lei,WANG Xin-hua,LIU Sheng,MA Liang,LU Ying..RNA interference targeting mu-opioid receptors reverses the inhibition of fentanyl on glucose-evoked insulin release of rat islets[J].中华医学杂志（英文版）,2010,123(24):3652-3657,6.
