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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of neuroscience research 2015-04, Vol.93 (4), p.666-677
Hauptverfasser: Sun, Yan-Na, Liu, Li-Bo, Xue, Yi-Xue, Wang, Ping
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 677
container_issue 4
container_start_page 666
container_title Journal of neuroscience research
container_volume 93
creator Sun, Yan-Na
Liu, Li-Bo
Xue, Yi-Xue
Wang, Ping
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.
doi_str_mv 10.1002/jnr.23511
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1660415179</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3588257481</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4161-c0e48ed53f0033a66ec62b7683b3859553d58011ef11e5f64c04573fcc6c2e553</originalsourceid><addsrcrecordid>eNqNkU1v1DAQhi0EokvhwB9AlrhwSeuJP5IcYdWWVqUIBOJo2c5EeEnsrZ2o7L_H3S09cGKk0Yw0zzvSzEvIa2AnwFh9ugnppOYS4AlZAeuaSkjRPCUrxhWrBIP6iLzIecMY6zrJn5OjWooaGmhXRJ8NA7o50zhQH_Iy-kBdnKwP2NM7P_-kvkeLIQakMVA7xthXNpmCWZOSx0S3mCY01o9-3pUdtPfG4uwdTWbOL8mzwYwZXz3UY_L9_Ozb-mN1_fnicv3-unICFFSOoWixl3xgjHOjFDpV20a13PJWdlLyXrYMAIeSclDCMSEbPjinXI1lfEzeHfZuU7xdMM968tnhOJqAcckalGICJDTdf6BSyhraPfr2H3QTlxTKIfeUaHgJKNSbB2qxE_Z6m_xk0k7__XIBTg_AnR9x9zgHpu_t08U-vbdPX9183TdFUR0UPs_4-1Fh0i-tGt5I_ePmQn86Z-2X9Ye17vgfpH2Zpw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1654733331</pqid></control><display><type>article</type><title>Effects of insulin combined with idebenone on blood-brain barrier permeability in diabetic rats</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Sun, Yan-Na ; Liu, Li-Bo ; Xue, Yi-Xue ; Wang, Ping</creator><creatorcontrib>Sun, Yan-Na ; Liu, Li-Bo ; Xue, Yi-Xue ; Wang, Ping</creatorcontrib><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><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 &amp; 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 &amp; 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 &amp; 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 &amp; 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 &amp; 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>
fulltext fulltext
identifier ISSN: 0360-4012
ispartof Journal of neuroscience research, 2015-04, Vol.93 (4), p.666-677
issn 0360-4012
1097-4547
language eng
recordid cdi_proquest_miscellaneous_1660415179
source MEDLINE; Wiley Online Library Journals Frontfile Complete
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
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T06%3A19%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effects%20of%20insulin%20combined%20with%20idebenone%20on%20blood-brain%20barrier%20permeability%20in%20diabetic%20rats&rft.jtitle=Journal%20of%20neuroscience%20research&rft.au=Sun,%20Yan-Na&rft.date=2015-04&rft.volume=93&rft.issue=4&rft.spage=666&rft.epage=677&rft.pages=666-677&rft.issn=0360-4012&rft.eissn=1097-4547&rft_id=info:doi/10.1002/jnr.23511&rft_dat=%3Cproquest_pubme%3E3588257481%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1654733331&rft_id=info:pmid/25421718&rfr_iscdi=true