Canagliflozin protects the cardiovascular system through effects on the gut environment in non-diabetic nephrectomized rats
Background The gut produces toxins that contribute to the cardiovascular complications of chronic kidney disease. Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor that is used as an anti-diabetic drug, has a weak inhibitory effect against SGLT1 and may affect the gut glucose concentr...
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| Veröffentlicht in: | Clinical and experimental nephrology 2023-04, Vol.27 (4), p.295-308 |
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| creator | Matsui, Ayumi Yoshifuji, Ayumi Irie, Junichiro Tajima, Takaya Uchiyama, Kiyotaka Itoh, Tomoaki Wakino, Shu Itoh, Hiroshi |
| description | Background
The gut produces toxins that contribute to the cardiovascular complications of chronic kidney disease. Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor that is used as an anti-diabetic drug, has a weak inhibitory effect against SGLT1 and may affect the gut glucose concentration and environment.
Methods
Here, we determined the effect of canagliflozin on the gut microbiota and the serum gut-derived uremic toxin concentrations in 5/6th nephrectomized (Nx) rats.
Results
Canagliflozin increased the colonic glucose concentration and restored the number of
Lactobacillus
bacteria, which was low in Nx rats. In addition, the expression of tight junction proteins in the ascending colon was low in Nx rats, and this was partially restored by canagliflozin. Furthermore, the serum concentrations of gut-derived uremic toxins were significantly increased by Nx and reduced by canagliflozin. Finally, the wall of the thoracic aorta was thicker and there was more cardiac interstitial fibrosis in Nx rats, and these defects were ameliorated by canagliflozin.
Conclusions
The increases in colonic glucose concentration,
Lactobacillus
numbers and tight junction protein expression, and the decreases in serum uremic toxin concentrations and cardiac interstitial fibrosis may have been caused by the inhibition of SGLT1 by canagliflozin because similar effects were not identified in tofogliflozin-treated rats. |
| doi_str_mv | 10.1007/s10157-022-02312-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2761978097</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2890338865</sourcerecordid><originalsourceid>FETCH-LOGICAL-c553t-d9e1fcd388a27776005a467b5c53f630e28c0a8eff88ca36f1059a770ee72eea3</originalsourceid><addsrcrecordid>eNp9kUFvVCEUhYnR2Fr9Ay4MiRs3z15geMDSTGpr0sSNrgnDu2-G5j0Ygddk6p-XzlRNXLggkNzvnHvIIeQtg48MQF0WBkyqDjhvRzDeHZ6Rc7YSqlPKmOftLVa8Y0qyM_KqlDsA0Eaal-RM9D1jjOtz8nPtottOYZzSQ4h0n1NFXwutO6Te5SGke1f8MrlMy6FUnNskp2W7oziORzLFI7xdKsV4H3KKM8ZKm1lMsRuC22ANnkbc73ITpDk84ECzq-U1eTG6qeCbp_uCfP989W19091-vf6y_nTbeSlF7QaDbPSD0NpxpVQPIN2qVxvppRh7Aci1B6dbHq29E_3IQBqnFCAqjujEBflw8m2_-7FgqXYOxeM0uYhpKZarnhmlwaiGvv8HvUtLji2d5dqAaCF62Sh-onxOpWQc7T6H2eWDZWAfq7Gnamyrxh6rsYcmevdkvWxmHP5IfnfRAHECShvFLea_u_9j-wtB_5yt</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2890338865</pqid></control><display><type>article</type><title>Canagliflozin protects the cardiovascular system through effects on the gut environment in non-diabetic nephrectomized rats</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Matsui, Ayumi ; Yoshifuji, Ayumi ; Irie, Junichiro ; Tajima, Takaya ; Uchiyama, Kiyotaka ; Itoh, Tomoaki ; Wakino, Shu ; Itoh, Hiroshi</creator><creatorcontrib>Matsui, Ayumi ; Yoshifuji, Ayumi ; Irie, Junichiro ; Tajima, Takaya ; Uchiyama, Kiyotaka ; Itoh, Tomoaki ; Wakino, Shu ; Itoh, Hiroshi</creatorcontrib><description>Background
The gut produces toxins that contribute to the cardiovascular complications of chronic kidney disease. Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor that is used as an anti-diabetic drug, has a weak inhibitory effect against SGLT1 and may affect the gut glucose concentration and environment.
Methods
Here, we determined the effect of canagliflozin on the gut microbiota and the serum gut-derived uremic toxin concentrations in 5/6th nephrectomized (Nx) rats.
Results
Canagliflozin increased the colonic glucose concentration and restored the number of
Lactobacillus
bacteria, which was low in Nx rats. In addition, the expression of tight junction proteins in the ascending colon was low in Nx rats, and this was partially restored by canagliflozin. Furthermore, the serum concentrations of gut-derived uremic toxins were significantly increased by Nx and reduced by canagliflozin. Finally, the wall of the thoracic aorta was thicker and there was more cardiac interstitial fibrosis in Nx rats, and these defects were ameliorated by canagliflozin.
Conclusions
The increases in colonic glucose concentration,
Lactobacillus
numbers and tight junction protein expression, and the decreases in serum uremic toxin concentrations and cardiac interstitial fibrosis may have been caused by the inhibition of SGLT1 by canagliflozin because similar effects were not identified in tofogliflozin-treated rats.</description><identifier>ISSN: 1342-1751</identifier><identifier>EISSN: 1437-7799</identifier><identifier>DOI: 10.1007/s10157-022-02312-y</identifier><identifier>PMID: 36611128</identifier><language>eng</language><publisher>Singapore: Springer Nature Singapore</publisher><subject>Animals ; Antidiabetics ; Aorta ; Canagliflozin - pharmacology ; Canagliflozin - therapeutic use ; Cardiovascular System ; Diabetes ; Diabetes mellitus ; Fibrosis ; Glucose ; Heart ; Intestinal microflora ; Kidney diseases ; Lactobacillus ; Medicine ; Medicine & Public Health ; Nephrology ; Original Article ; Rats ; Sodium-glucose cotransporter ; Sodium-Glucose Transporter 2 Inhibitors - pharmacology ; Thorax ; Urology</subject><ispartof>Clinical and experimental nephrology, 2023-04, Vol.27 (4), p.295-308</ispartof><rights>The Author(s), under exclusive licence to The Japanese Society of Nephrology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c553t-d9e1fcd388a27776005a467b5c53f630e28c0a8eff88ca36f1059a770ee72eea3</citedby><cites>FETCH-LOGICAL-c553t-d9e1fcd388a27776005a467b5c53f630e28c0a8eff88ca36f1059a770ee72eea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10157-022-02312-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10157-022-02312-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36611128$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Matsui, Ayumi</creatorcontrib><creatorcontrib>Yoshifuji, Ayumi</creatorcontrib><creatorcontrib>Irie, Junichiro</creatorcontrib><creatorcontrib>Tajima, Takaya</creatorcontrib><creatorcontrib>Uchiyama, Kiyotaka</creatorcontrib><creatorcontrib>Itoh, Tomoaki</creatorcontrib><creatorcontrib>Wakino, Shu</creatorcontrib><creatorcontrib>Itoh, Hiroshi</creatorcontrib><title>Canagliflozin protects the cardiovascular system through effects on the gut environment in non-diabetic nephrectomized rats</title><title>Clinical and experimental nephrology</title><addtitle>Clin Exp Nephrol</addtitle><addtitle>Clin Exp Nephrol</addtitle><description>Background
The gut produces toxins that contribute to the cardiovascular complications of chronic kidney disease. Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor that is used as an anti-diabetic drug, has a weak inhibitory effect against SGLT1 and may affect the gut glucose concentration and environment.
Methods
Here, we determined the effect of canagliflozin on the gut microbiota and the serum gut-derived uremic toxin concentrations in 5/6th nephrectomized (Nx) rats.
Results
Canagliflozin increased the colonic glucose concentration and restored the number of
Lactobacillus
bacteria, which was low in Nx rats. In addition, the expression of tight junction proteins in the ascending colon was low in Nx rats, and this was partially restored by canagliflozin. Furthermore, the serum concentrations of gut-derived uremic toxins were significantly increased by Nx and reduced by canagliflozin. Finally, the wall of the thoracic aorta was thicker and there was more cardiac interstitial fibrosis in Nx rats, and these defects were ameliorated by canagliflozin.
Conclusions
The increases in colonic glucose concentration,
Lactobacillus
numbers and tight junction protein expression, and the decreases in serum uremic toxin concentrations and cardiac interstitial fibrosis may have been caused by the inhibition of SGLT1 by canagliflozin because similar effects were not identified in tofogliflozin-treated rats.</description><subject>Animals</subject><subject>Antidiabetics</subject><subject>Aorta</subject><subject>Canagliflozin - pharmacology</subject><subject>Canagliflozin - therapeutic use</subject><subject>Cardiovascular System</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Fibrosis</subject><subject>Glucose</subject><subject>Heart</subject><subject>Intestinal microflora</subject><subject>Kidney diseases</subject><subject>Lactobacillus</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Nephrology</subject><subject>Original Article</subject><subject>Rats</subject><subject>Sodium-glucose cotransporter</subject><subject>Sodium-Glucose Transporter 2 Inhibitors - pharmacology</subject><subject>Thorax</subject><subject>Urology</subject><issn>1342-1751</issn><issn>1437-7799</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kUFvVCEUhYnR2Fr9Ay4MiRs3z15geMDSTGpr0sSNrgnDu2-G5j0Ygddk6p-XzlRNXLggkNzvnHvIIeQtg48MQF0WBkyqDjhvRzDeHZ6Rc7YSqlPKmOftLVa8Y0qyM_KqlDsA0Eaal-RM9D1jjOtz8nPtottOYZzSQ4h0n1NFXwutO6Te5SGke1f8MrlMy6FUnNskp2W7oziORzLFI7xdKsV4H3KKM8ZKm1lMsRuC22ANnkbc73ITpDk84ECzq-U1eTG6qeCbp_uCfP989W19091-vf6y_nTbeSlF7QaDbPSD0NpxpVQPIN2qVxvppRh7Aci1B6dbHq29E_3IQBqnFCAqjujEBflw8m2_-7FgqXYOxeM0uYhpKZarnhmlwaiGvv8HvUtLji2d5dqAaCF62Sh-onxOpWQc7T6H2eWDZWAfq7Gnamyrxh6rsYcmevdkvWxmHP5IfnfRAHECShvFLea_u_9j-wtB_5yt</recordid><startdate>20230401</startdate><enddate>20230401</enddate><creator>Matsui, Ayumi</creator><creator>Yoshifuji, Ayumi</creator><creator>Irie, Junichiro</creator><creator>Tajima, Takaya</creator><creator>Uchiyama, Kiyotaka</creator><creator>Itoh, Tomoaki</creator><creator>Wakino, Shu</creator><creator>Itoh, Hiroshi</creator><general>Springer Nature Singapore</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20230401</creationdate><title>Canagliflozin protects the cardiovascular system through effects on the gut environment in non-diabetic nephrectomized rats</title><author>Matsui, Ayumi ; Yoshifuji, Ayumi ; Irie, Junichiro ; Tajima, Takaya ; Uchiyama, Kiyotaka ; Itoh, Tomoaki ; Wakino, Shu ; Itoh, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c553t-d9e1fcd388a27776005a467b5c53f630e28c0a8eff88ca36f1059a770ee72eea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Antidiabetics</topic><topic>Aorta</topic><topic>Canagliflozin - pharmacology</topic><topic>Canagliflozin - therapeutic use</topic><topic>Cardiovascular System</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Fibrosis</topic><topic>Glucose</topic><topic>Heart</topic><topic>Intestinal microflora</topic><topic>Kidney diseases</topic><topic>Lactobacillus</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Nephrology</topic><topic>Original Article</topic><topic>Rats</topic><topic>Sodium-glucose cotransporter</topic><topic>Sodium-Glucose Transporter 2 Inhibitors - pharmacology</topic><topic>Thorax</topic><topic>Urology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Matsui, Ayumi</creatorcontrib><creatorcontrib>Yoshifuji, Ayumi</creatorcontrib><creatorcontrib>Irie, Junichiro</creatorcontrib><creatorcontrib>Tajima, Takaya</creatorcontrib><creatorcontrib>Uchiyama, Kiyotaka</creatorcontrib><creatorcontrib>Itoh, Tomoaki</creatorcontrib><creatorcontrib>Wakino, Shu</creatorcontrib><creatorcontrib>Itoh, Hiroshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical and experimental nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matsui, Ayumi</au><au>Yoshifuji, Ayumi</au><au>Irie, Junichiro</au><au>Tajima, Takaya</au><au>Uchiyama, Kiyotaka</au><au>Itoh, Tomoaki</au><au>Wakino, Shu</au><au>Itoh, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Canagliflozin protects the cardiovascular system through effects on the gut environment in non-diabetic nephrectomized rats</atitle><jtitle>Clinical and experimental nephrology</jtitle><stitle>Clin Exp Nephrol</stitle><addtitle>Clin Exp Nephrol</addtitle><date>2023-04-01</date><risdate>2023</risdate><volume>27</volume><issue>4</issue><spage>295</spage><epage>308</epage><pages>295-308</pages><issn>1342-1751</issn><eissn>1437-7799</eissn><abstract>Background
The gut produces toxins that contribute to the cardiovascular complications of chronic kidney disease. Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor that is used as an anti-diabetic drug, has a weak inhibitory effect against SGLT1 and may affect the gut glucose concentration and environment.
Methods
Here, we determined the effect of canagliflozin on the gut microbiota and the serum gut-derived uremic toxin concentrations in 5/6th nephrectomized (Nx) rats.
Results
Canagliflozin increased the colonic glucose concentration and restored the number of
Lactobacillus
bacteria, which was low in Nx rats. In addition, the expression of tight junction proteins in the ascending colon was low in Nx rats, and this was partially restored by canagliflozin. Furthermore, the serum concentrations of gut-derived uremic toxins were significantly increased by Nx and reduced by canagliflozin. Finally, the wall of the thoracic aorta was thicker and there was more cardiac interstitial fibrosis in Nx rats, and these defects were ameliorated by canagliflozin.
Conclusions
The increases in colonic glucose concentration,
Lactobacillus
numbers and tight junction protein expression, and the decreases in serum uremic toxin concentrations and cardiac interstitial fibrosis may have been caused by the inhibition of SGLT1 by canagliflozin because similar effects were not identified in tofogliflozin-treated rats.</abstract><cop>Singapore</cop><pub>Springer Nature Singapore</pub><pmid>36611128</pmid><doi>10.1007/s10157-022-02312-y</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antidiabetics Aorta Canagliflozin - pharmacology Canagliflozin - therapeutic use Cardiovascular System Diabetes Diabetes mellitus Fibrosis Glucose Heart Intestinal microflora Kidney diseases Lactobacillus Medicine Medicine & Public Health Nephrology Original Article Rats Sodium-glucose cotransporter Sodium-Glucose Transporter 2 Inhibitors - pharmacology Thorax Urology |
| title | Canagliflozin protects the cardiovascular system through effects on the gut environment in non-diabetic nephrectomized rats |
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