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Glucose-responsive erythrocyte-bound nanoparticles for continuously modulated insulin release

Nano Research 2022年第6期15卷 5205-5215页

作者： Xiaomin Xu Yani Xu Yuai Li Min Li Leilei Wang Qiang Zhang Bingjie Zhou Qing Lin Tao Gong Xun Sun Zhirong Zhang Ling Zhang Key laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041China Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Glucose-responsive closed-loop insulin delivery systems represent a promising treatment strategy for diabetes,but current systems generally cannot achieve long-term *** this study,we designed an erythrocyte-biomimetic glucose-responsive system(EGRS)by coupling glucose-responsive nanoparticles(GRNs)to red blood cells;these nanoparticles exhibited the dual functions of glucose-responsiveness and persistent presence in *** are generated by encapsulating with insulin through ion crosslinking,followed by coloading with glucose oxidase(GOx)and catalase(CAT),a process that endows the nanoparticles with ***,the GRNs are coupled with red blood cells to camouflage them from the immune system,therefore,these erythrocyte-coupled GRNs can circulate in the blood for a long *** conditions of hyperglycemia,GOx acts on blood glucose to produce gluconic acid,which causes the rupture of GRNs and efficient release of ***,insulin is only released at the basic rate during ***,EGRS can efficiently and continuously respond to hyperglycemia to maintain blood glucose levels within the normal range.

关键词： glucose-responsive erythrocyte-biomimetic insulin release blood glucose control diabetes

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Fentanyl inhibits glucose-stimulated insulin release from β-cells in rat pancreatic islets

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World Journal of Gastroenterology 2009年第33期15卷 4163-4169页

作者： Tao-Lai Qian Xin-Hua Wang Sheng Liu Liang Ma Ying Lu Department of Pain Management Shanghai East Hospital Tongji University Shanghai 200120 China Department of Anesthesia Shanghai East HospitalTongji University Shanghai 200120 China Cell Therapy Center Shanghai East Hospital Tongji University Shanghai 200120 China Central Laboratory Shanghai East Hospital Tongji University Shanghai 200120 China

AIM： TO explore the effects of fentanyl on insulin release from freshly isolated rat pancreatic islets in static culture. METHODS： Islets were isolated from the pancreas of mature Sprague Dawley rats by common bile duct intraductal collagenase V digestion and were purified by discontinuous Ficoll density gradient centrifugation. The islets were divided into four groups according to the fentanyl concentration： control group （0 ng/mL）, group I （0.3 ng/mL）, group I （3.0 ng/mL）, and group III （30 ng/mL）. In each group, the islets were co-cultured for 48 h with drugs under static conditions with fentanyl alone, fentanyl ＋ 0.1 μg/mL naloxone or fentanyl ＋ 1.0 μg/mL naloxone. Cell viability was assessed by the MTT assay. insulin release in response to low and high concentrations （2.8 mmol/L and 16.7 mmol/L, respectively） of glucose was investigated and electron microscopy morphological assessment was performed. RESULTS： Low- and high-glucose-stimulated insulin release in the control group was significantly higher than in groups I and II （62.33 ± 9.67 μIU vs 47.75 ± 8.47 μIU, 39.67 ± 6.18 μIU and 125.5 ± 22.04 μIU vs 96.17 ± 14.17 μIU, 75.17 ± 13.57 μIU, respectively, P 〈 0.01） and was lowest in group III （P 〈 0.01）. After adding 1 μg/mL naloxone, insulin release in groups II and II was not different from the control group. Electron microscopy studies showed that the islets were damaged by 30 ng/ml fentanyl. CONCLUSION： Fentanyl inhibited glucose-stimulated insulin release from rat islets, which could be prevented by naloxone. Higher concentrations of fentanyl significantly damaged β-cells of rat islets.

关键词： Fentanyl Inhibition insulin release Islets

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RNA interference targeting mu-opioid receptors reverses the inhibition of fentanyl on glucose-evoked insulin release of rat islets

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Chinese Medical Journal 2010年第24期123卷 3652-3657页

作者： QIAN Tao-lai ZHANG Lei WANG Xin-hua LIU Sheng MA Liang LU Ying Department of Anesthesiology Shenzhen Shekou People's Hospital Shenzhen Guangdong 518067 China Pain Management Department Shanghai Dongfang Hospital Tongji University Shanghai 200120 China Department of Anesthesiology Shanghai Dongfang Hospital Tongji University Shanghai 200120 China Cell Therapy Center Shanghai Dongfang Hospital Tongji University Shanghai 200120 China Central Laboratory Shanghai Dongfang Hospital Tongji University Shanghai 200120 China

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 *** 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 *** 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 release

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The role of endosomal cholesterol trafficking protein, StAR-related lipid transfer domain 3 （StarD3/MLN64）, in BRIN-BD11 insulinoma cells

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Protein & Cell 2016年第11期7卷 833-838页

作者： Joana Borges Pinto Annette Graham Department of Life Sciences School of Health and Life Sciences Glasgow Caledonian University Glasgow G4 0BA UK WolfsonWohl Cancer Research Centre Institute of Cancer Sciences University of Glasgow Switchback Road Bearsden Glasgow G61 1QH UK

Dear Editor, insulin secretion by pancreatic β-cells is modulated by altering the cellular content and distribution of cholesterol, which is tightly regulated by a network of transcription factors, enzymes, receptors, transporters and cholesterol trafficking proteins. Inhibition of cellular biosynthesis by ＇statin＇ drugs, or depletion of plasma membrane cholesterol by methyl-β-cyclodextrin （MCD）, reduce glucose-stimulated insulin secretion （GSIS） and content in β-cells and islets;

关键词： Cholesterol Lutein insulin release Cholesterol Efflux Cholesterol Depletion

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Development of islet organoids from human induced pluripotent stem cells in a cross-linked collagen scaffold

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Cell Regeneration 2021年第1期10卷 388-399页

作者： Shruti Sandilya Shashi Singh CSIR-Centre for Cellular and Molecular Biology Uppal RoadHyderabad 500007India

Islets organoids would have value in the cell replacement therapy for diabetes apart from usual personalized drug screening *** of a large number of Islets like clusters,with ability to respond to glucose stimulation appears to be an ideal *** this study we have generated islet organoids with the ability to respond to glucose stimulation by insulin *** source of the cells was an iPSC cell line differentiated into the pancreatic *** cells were assembled in matrigel or cross-linked collagen scaffold and compared for their efficacy to release insulin upon stimulation with *** assembled organoids were examined by immunohistochemistry and expression of the relevant marker *** organoids showed expression of islet like markers in both-matrigel and crosslinked collagen *** islet organoids in both the cases showed release of insulin upon stimulation with *** crosslinked collagen scaffold is quite stable and supports islet cells growth and function.

关键词： Endocrine Exocrine Marker genes Crosslinked collagen Functional insulin release

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Effect of Sanhuang Jiangtang (三黄降糖) Recipe on insulin Peripheral Resistance in Type Ⅱ Diabetes Mellitus

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Chinese Journal of Integrative Medicine 1999年第1期5卷 36-40页

作者：朱章志熊曼琪林安钟蔡文就陈芝喜沈穗婷龙新生糜军伍游雅何敏

Objective: To observe the effect of Sanhuang Jiangtang recipe (三黄降糖, SAT) on insulinperipheral resistance in Type Ⅱdiabetes mellitus (DM). Methods:Ninety-five patients with type Ⅱ DM wererandomly divided into two groups. Fifty-three cases of SHJT group were given decoction and tablets of SAT orally for 4 -- 6 months. The efficacy was compared with that of 42 cases treated with Glipizide as the *** and after treatment standard steamed bread meal test was performed to measure the insulin peripheralsensitivity, insulin release to glucose and insulin sensitivity index. Results: (1 ) The total effective rates of improving insulin peripheral resistance and reducing blood sugar in SHJT group were 79. 2 % and 80. I %, whichwas equivalent to levels in the control group, but SAT recipe was more effective in relieving symptoms of Qideficiency and signs of blood stasis. (2) In SalT group, the insulin peripheral sensitivity and insulin sensitivityindex were significantly increased (P insulin release to glucose was blunted. (3 )The lowering of bloodsugar in SHJT group was significantly negative correlated with the changing of degree of insulin peripheral sensitivity and index of insulin sensitivity (P insulin area. Conclusion: Itsuggested that the treatment of SHJT recipe might decrease insulin peripheral resistance (partial reversal) bymeans of reducing hyperinsulinemia and improving insulin sensitivity.

关键词： type Ⅱ diabetes mellitus Sanhuang Jiangtang recipe insulin resistance insulin peripheralSensitivity insulin release

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