Effects of insulin combined with idebenone on blood-brain barrier permeability in diabetic rats
This study investigates the effect of insulin combined with idebenone on blood–brain barrier (BBB) permeability in experimental streptozotocin‐induced diabetic rats as well as the underlying mechanisms. With a diabetic rat model, we show that insulin and idebenone normalize body weight and water int...
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description | This study investigates the effect of insulin combined with idebenone on blood–brain barrier (BBB) permeability in experimental streptozotocin‐induced diabetic rats as well as the underlying mechanisms. With a diabetic rat model, we show that insulin and idebenone normalize body weight and water intake and restore BBB permeability and that their combination displays a synergistic effect. The results from transmission electron microscopy show that the combination of insulin and idebenone significantly closed the tight junction (TJ) in diabetic rats. The results from Western blotting in diabetic rats show that the upregulation of TJ‐associated proteins occludin, and zonula occludens (ZO)‐1 caused by the combination of insulin and idebenone is more remarkable than that with either agent alone. In addition, the activations of reactive oxygen species (ROS) and advanced glycation end products (AGEs) and the expression levels of receptors for advanced glycation end‐products (RAGE) and nuclear factor‐κB (NF‐κB) were significantly decreased after treatment with insulin and idebenone in diabetic rats. These results suggest that the combination of insulin and idebenone could decrease the BBB permeability in diabetic rats by upregulating the expression of occludin, claudin‐5, and ZO‐1 and that the ROS/AGE/RAGE/NF‐κB signal pathway might be involved in the process. © 2014 Wiley Periodicals, Inc. |
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With a diabetic rat model, we show that insulin and idebenone normalize body weight and water intake and restore BBB permeability and that their combination displays a synergistic effect. The results from transmission electron microscopy show that the combination of insulin and idebenone significantly closed the tight junction (TJ) in diabetic rats. The results from Western blotting in diabetic rats show that the upregulation of TJ‐associated proteins occludin, and zonula occludens (ZO)‐1 caused by the combination of insulin and idebenone is more remarkable than that with either agent alone. In addition, the activations of reactive oxygen species (ROS) and advanced glycation end products (AGEs) and the expression levels of receptors for advanced glycation end‐products (RAGE) and nuclear factor‐κB (NF‐κB) were significantly decreased after treatment with insulin and idebenone in diabetic rats. These results suggest that the combination of insulin and idebenone could decrease the BBB permeability in diabetic rats by upregulating the expression of occludin, claudin‐5, and ZO‐1 and that the ROS/AGE/RAGE/NF‐κB signal pathway might be involved in the process. © 2014 Wiley Periodicals, Inc.</description><identifier>ISSN: 0360-4012</identifier><identifier>EISSN: 1097-4547</identifier><identifier>DOI: 10.1002/jnr.23511</identifier><identifier>PMID: 25421718</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Animals ; Antioxidants - therapeutic use ; blood-brain barrier ; Blood-Brain Barrier - drug effects ; Blood-Brain Barrier - physiopathology ; Blood-Brain Barrier - ultrastructure ; Capillary Permeability - drug effects ; diabetes ; Diabetes Mellitus, Experimental - chemically induced ; Diabetes Mellitus, Experimental - drug therapy ; Diabetes Mellitus, Experimental - pathology ; Disease Models, Animal ; Hypoglycemic Agents - therapeutic use ; idebenone ; insulin ; Insulin - therapeutic use ; Male ; Microscopy, Electron, Transmission ; Nucleoproteins - metabolism ; Rats ; Rats, Wistar ; Reactive Oxygen Species - metabolism ; Statistics, Nonparametric ; tight junction ; Ubiquinone - analogs & derivatives ; Ubiquinone - therapeutic use</subject><ispartof>Journal of neuroscience research, 2015-04, Vol.93 (4), p.666-677</ispartof><rights>2014 Wiley Periodicals, Inc.</rights><rights>2015 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4161-c0e48ed53f0033a66ec62b7683b3859553d58011ef11e5f64c04573fcc6c2e553</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjnr.23511$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjnr.23511$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25421718$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Yan-Na</creatorcontrib><creatorcontrib>Liu, Li-Bo</creatorcontrib><creatorcontrib>Xue, Yi-Xue</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><title>Effects of insulin combined with idebenone on blood-brain barrier permeability in diabetic rats</title><title>Journal of neuroscience research</title><addtitle>Journal of Neuroscience Research</addtitle><description>This study investigates the effect of insulin combined with idebenone on blood–brain barrier (BBB) permeability in experimental streptozotocin‐induced diabetic rats as well as the underlying mechanisms. With a diabetic rat model, we show that insulin and idebenone normalize body weight and water intake and restore BBB permeability and that their combination displays a synergistic effect. The results from transmission electron microscopy show that the combination of insulin and idebenone significantly closed the tight junction (TJ) in diabetic rats. The results from Western blotting in diabetic rats show that the upregulation of TJ‐associated proteins occludin, and zonula occludens (ZO)‐1 caused by the combination of insulin and idebenone is more remarkable than that with either agent alone. In addition, the activations of reactive oxygen species (ROS) and advanced glycation end products (AGEs) and the expression levels of receptors for advanced glycation end‐products (RAGE) and nuclear factor‐κB (NF‐κB) were significantly decreased after treatment with insulin and idebenone in diabetic rats. These results suggest that the combination of insulin and idebenone could decrease the BBB permeability in diabetic rats by upregulating the expression of occludin, claudin‐5, and ZO‐1 and that the ROS/AGE/RAGE/NF‐κB signal pathway might be involved in the process. © 2014 Wiley Periodicals, Inc.</description><subject>Animals</subject><subject>Antioxidants - therapeutic use</subject><subject>blood-brain barrier</subject><subject>Blood-Brain Barrier - drug effects</subject><subject>Blood-Brain Barrier - physiopathology</subject><subject>Blood-Brain Barrier - ultrastructure</subject><subject>Capillary Permeability - drug effects</subject><subject>diabetes</subject><subject>Diabetes Mellitus, Experimental - chemically induced</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Diabetes Mellitus, Experimental - pathology</subject><subject>Disease Models, Animal</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>idebenone</subject><subject>insulin</subject><subject>Insulin - therapeutic use</subject><subject>Male</subject><subject>Microscopy, Electron, Transmission</subject><subject>Nucleoproteins - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Statistics, Nonparametric</subject><subject>tight junction</subject><subject>Ubiquinone - analogs & derivatives</subject><subject>Ubiquinone - therapeutic use</subject><issn>0360-4012</issn><issn>1097-4547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi0EokvhwB9AlrhwSeuJP5IcYdWWVqUIBOJo2c5EeEnsrZ2o7L_H3S09cGKk0Yw0zzvSzEvIa2AnwFh9ugnppOYS4AlZAeuaSkjRPCUrxhWrBIP6iLzIecMY6zrJn5OjWooaGmhXRJ8NA7o50zhQH_Iy-kBdnKwP2NM7P_-kvkeLIQakMVA7xthXNpmCWZOSx0S3mCY01o9-3pUdtPfG4uwdTWbOL8mzwYwZXz3UY_L9_Ozb-mN1_fnicv3-unICFFSOoWixl3xgjHOjFDpV20a13PJWdlLyXrYMAIeSclDCMSEbPjinXI1lfEzeHfZuU7xdMM968tnhOJqAcckalGICJDTdf6BSyhraPfr2H3QTlxTKIfeUaHgJKNSbB2qxE_Z6m_xk0k7__XIBTg_AnR9x9zgHpu_t08U-vbdPX9183TdFUR0UPs_4-1Fh0i-tGt5I_ePmQn86Z-2X9Ye17vgfpH2Zpw</recordid><startdate>201504</startdate><enddate>201504</enddate><creator>Sun, Yan-Na</creator><creator>Liu, Li-Bo</creator><creator>Xue, Yi-Xue</creator><creator>Wang, Ping</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201504</creationdate><title>Effects of insulin combined with idebenone on blood-brain barrier permeability in diabetic rats</title><author>Sun, Yan-Na ; Liu, Li-Bo ; Xue, Yi-Xue ; Wang, Ping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4161-c0e48ed53f0033a66ec62b7683b3859553d58011ef11e5f64c04573fcc6c2e553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antioxidants - therapeutic use</topic><topic>blood-brain barrier</topic><topic>Blood-Brain Barrier - drug effects</topic><topic>Blood-Brain Barrier - physiopathology</topic><topic>Blood-Brain Barrier - ultrastructure</topic><topic>Capillary Permeability - drug effects</topic><topic>diabetes</topic><topic>Diabetes Mellitus, Experimental - chemically induced</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Diabetes Mellitus, Experimental - pathology</topic><topic>Disease Models, Animal</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>idebenone</topic><topic>insulin</topic><topic>Insulin - therapeutic use</topic><topic>Male</topic><topic>Microscopy, Electron, Transmission</topic><topic>Nucleoproteins - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Statistics, Nonparametric</topic><topic>tight junction</topic><topic>Ubiquinone - analogs & derivatives</topic><topic>Ubiquinone - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Yan-Na</creatorcontrib><creatorcontrib>Liu, Li-Bo</creatorcontrib><creatorcontrib>Xue, Yi-Xue</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neuroscience research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Yan-Na</au><au>Liu, Li-Bo</au><au>Xue, Yi-Xue</au><au>Wang, Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of insulin combined with idebenone on blood-brain barrier permeability in diabetic rats</atitle><jtitle>Journal of neuroscience research</jtitle><addtitle>Journal of Neuroscience Research</addtitle><date>2015-04</date><risdate>2015</risdate><volume>93</volume><issue>4</issue><spage>666</spage><epage>677</epage><pages>666-677</pages><issn>0360-4012</issn><eissn>1097-4547</eissn><abstract>This study investigates the effect of insulin combined with idebenone on blood–brain barrier (BBB) permeability in experimental streptozotocin‐induced diabetic rats as well as the underlying mechanisms. With a diabetic rat model, we show that insulin and idebenone normalize body weight and water intake and restore BBB permeability and that their combination displays a synergistic effect. The results from transmission electron microscopy show that the combination of insulin and idebenone significantly closed the tight junction (TJ) in diabetic rats. The results from Western blotting in diabetic rats show that the upregulation of TJ‐associated proteins occludin, and zonula occludens (ZO)‐1 caused by the combination of insulin and idebenone is more remarkable than that with either agent alone. In addition, the activations of reactive oxygen species (ROS) and advanced glycation end products (AGEs) and the expression levels of receptors for advanced glycation end‐products (RAGE) and nuclear factor‐κB (NF‐κB) were significantly decreased after treatment with insulin and idebenone in diabetic rats. These results suggest that the combination of insulin and idebenone could decrease the BBB permeability in diabetic rats by upregulating the expression of occludin, claudin‐5, and ZO‐1 and that the ROS/AGE/RAGE/NF‐κB signal pathway might be involved in the process. © 2014 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>25421718</pmid><doi>10.1002/jnr.23511</doi><tpages>12</tpages></addata></record> |
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subjects | Animals Antioxidants - therapeutic use blood-brain barrier Blood-Brain Barrier - drug effects Blood-Brain Barrier - physiopathology Blood-Brain Barrier - ultrastructure Capillary Permeability - drug effects diabetes Diabetes Mellitus, Experimental - chemically induced Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - pathology Disease Models, Animal Hypoglycemic Agents - therapeutic use idebenone insulin Insulin - therapeutic use Male Microscopy, Electron, Transmission Nucleoproteins - metabolism Rats Rats, Wistar Reactive Oxygen Species - metabolism Statistics, Nonparametric tight junction Ubiquinone - analogs & derivatives Ubiquinone - therapeutic use |
title | Effects of insulin combined with idebenone on blood-brain barrier permeability in diabetic rats |
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