Renoprotective effect of GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease in spontaneously diabetic Torii fatty rats
Background The aim of this study is to investigate the renoprotective effect of the GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease (DKD) using an animal model of type 2 diabetes with several metabolic disorders. Methods Male 8-week-old spontaneously diabetic Torii (SDT)...
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| Veröffentlicht in: | Clinical and experimental nephrology 2021-04, Vol.25 (4), p.365-375 |
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| creator | Yamada, Shohei Tanabe, Jun Ogura, Yuji Nagai, Yoshio Sugaya, Takeshi Ohata, Keiichi Natsuki, Yasunori Ichikawa, Daisuke Watanabe, Shiika Inoue, Kazuho Hoshino, Seiko Kimura, Kenjiro Shibagaki, Yugo Kamijo-Ikemori, Atsuko |
| description | Background
The aim of this study is to investigate the renoprotective effect of the GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease (DKD) using an animal model of type 2 diabetes with several metabolic disorders.
Methods
Male 8-week-old spontaneously diabetic Torii (SDT) fatty rats (
n
= 19) were randomly assigned to three groups. The liraglutide group (
n
= 6) was injected subcutaneously with liraglutide. Another treatment group (
n
= 6) received subcutaneous insulin against hyperglycemia and hydralazine against hypertension for matching blood glucose levels and blood pressure with the liraglutide group. The control groups of SDT fatty (
n
= 7) and non-diabetic Sprague–Dawley rats (
n
= 7) were injected only with a vehicle.
Results
The control group of SDT fatty rats exhibited hyperglycemia, obesity, hypertension, hyperlipidemia, glomerular sclerosis, and tubulointerstitial injury with high urinary albumin and L-FABP levels. Liraglutide treatment reduced body weight, food intake, blood glucose and blood pressure levels, as well as ameliorated renal pathologic findings with lower urinary albumin and L-FABP levels. Liraglutide increased expressions of phosphorylated (p)-eNOS and p-AMPK in glomeruli, downregulated renal expression of p-mTOR, and increased renal expressions of LC3B-II, suggesting activation of autophagy. However, these effects were not caused by the treatments with insulin and hydralazine, despite comparable levels of hyperglycemia and hypertension to those achieved with liraglutide treatment.
Conclusions
Liraglutide may exert a renoprotective effect via prevention of glomerular endothelial abnormality and preservation of autophagy in early-phase DKD, independent of blood glucose, and blood pressure levels. |
| doi_str_mv | 10.1007/s10157-020-02007-2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2476129069</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2476129069</sourcerecordid><originalsourceid>FETCH-LOGICAL-c520t-7984d4b4f898c7497ae6c9298ef97534ccc8a95065a0557a4a5972ec85a8d7c03</originalsourceid><addsrcrecordid>eNp9kcFu1DAQhiMEoqXwAhyQJS4cahg7dhwfUVVapJWoqnK2vM5kccnGwXYq5Sn6ynhJaSUOHKwZj7_5PfZfVW8ZfGQA6lNiwKSiwOGwQFH-rDpmolZUKa2fl7wWnDIl2VH1KqVbAGi11C-ro7oWoFXDjqv7axzDFENGl_0dEuz7kpHQk4vNFWUkosMph0jsLow-5VMy-Gh3w5x9h6fEjwRtHBY6_bAJSeftFrN35KfvRlzKPuGhXrA0hTHbEcOchuUJvAnRe9LbnBcSbU6vqxe9HRK-eYgn1fcv5zdnl3Tz7eLr2ecNdZJDpkq3ohNb0be6dUpoZbFxmusWe61kLZxzrdUSGmlBSmWFlVpxdK20bacc1CfVh1W3vP3XjCmbvU8Oh2Ed0XBRvodraHRB3_-D3oY5jmU6wyWwpmG1bgrFV8rFkFLE3kzR721cDANzsMusdplilfljl-Gl6d2D9LzdY_fY8tefAtQrkMrRuMP4dPd_ZH8D-QuhFQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2501661396</pqid></control><display><type>article</type><title>Renoprotective effect of GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease in spontaneously diabetic Torii fatty rats</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>Yamada, Shohei ; Tanabe, Jun ; Ogura, Yuji ; Nagai, Yoshio ; Sugaya, Takeshi ; Ohata, Keiichi ; Natsuki, Yasunori ; Ichikawa, Daisuke ; Watanabe, Shiika ; Inoue, Kazuho ; Hoshino, Seiko ; Kimura, Kenjiro ; Shibagaki, Yugo ; Kamijo-Ikemori, Atsuko</creator><creatorcontrib>Yamada, Shohei ; Tanabe, Jun ; Ogura, Yuji ; Nagai, Yoshio ; Sugaya, Takeshi ; Ohata, Keiichi ; Natsuki, Yasunori ; Ichikawa, Daisuke ; Watanabe, Shiika ; Inoue, Kazuho ; Hoshino, Seiko ; Kimura, Kenjiro ; Shibagaki, Yugo ; Kamijo-Ikemori, Atsuko</creatorcontrib><description>Background
The aim of this study is to investigate the renoprotective effect of the GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease (DKD) using an animal model of type 2 diabetes with several metabolic disorders.
Methods
Male 8-week-old spontaneously diabetic Torii (SDT) fatty rats (
n
= 19) were randomly assigned to three groups. The liraglutide group (
n
= 6) was injected subcutaneously with liraglutide. Another treatment group (
n
= 6) received subcutaneous insulin against hyperglycemia and hydralazine against hypertension for matching blood glucose levels and blood pressure with the liraglutide group. The control groups of SDT fatty (
n
= 7) and non-diabetic Sprague–Dawley rats (
n
= 7) were injected only with a vehicle.
Results
The control group of SDT fatty rats exhibited hyperglycemia, obesity, hypertension, hyperlipidemia, glomerular sclerosis, and tubulointerstitial injury with high urinary albumin and L-FABP levels. Liraglutide treatment reduced body weight, food intake, blood glucose and blood pressure levels, as well as ameliorated renal pathologic findings with lower urinary albumin and L-FABP levels. Liraglutide increased expressions of phosphorylated (p)-eNOS and p-AMPK in glomeruli, downregulated renal expression of p-mTOR, and increased renal expressions of LC3B-II, suggesting activation of autophagy. However, these effects were not caused by the treatments with insulin and hydralazine, despite comparable levels of hyperglycemia and hypertension to those achieved with liraglutide treatment.
Conclusions
Liraglutide may exert a renoprotective effect via prevention of glomerular endothelial abnormality and preservation of autophagy in early-phase DKD, independent of blood glucose, and blood pressure levels.</description><identifier>ISSN: 1342-1751</identifier><identifier>EISSN: 1437-7799</identifier><identifier>DOI: 10.1007/s10157-020-02007-2</identifier><identifier>PMID: 33409761</identifier><language>eng</language><publisher>Singapore: Springer Singapore</publisher><subject>Agonists ; Albumin ; Albuminuria - physiopathology ; Albuminuria - prevention & control ; Animal models ; Animals ; Antidiabetics ; Autophagy ; Autophagy - drug effects ; Biomarkers - blood ; Blood glucose ; Blood Glucose - drug effects ; Blood Glucose - metabolism ; Blood pressure ; Blood Pressure - drug effects ; Body weight ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes Mellitus, Type 2 - physiopathology ; Diabetic Nephropathies - metabolism ; Diabetic Nephropathies - pathology ; Diabetic Nephropathies - physiopathology ; Diabetic Nephropathies - prevention & control ; Diabetic nephropathy ; Disease Models, Animal ; Fatty acid-binding protein ; Food intake ; GLP-1 receptor agonists ; Glucagon-Like Peptide-1 Receptor - agonists ; Glucagon-Like Peptide-1 Receptor - metabolism ; Glucose ; Hyperglycemia ; Hyperlipidemia ; Hypertension ; Hypoglycemic Agents - pharmacology ; Incretins - pharmacology ; Insulin ; Kidney - drug effects ; Kidney - metabolism ; Kidney - pathology ; Kidney - physiopathology ; Kidney diseases ; Liraglutide - pharmacology ; Male ; Medicine ; Medicine & Public Health ; Metabolic disorders ; Nephrology ; Original Article ; Phagocytosis ; Rats ; Rats, Inbred Strains ; Sclerosis ; Signal Transduction ; TOR protein ; Urology</subject><ispartof>Clinical and experimental nephrology, 2021-04, Vol.25 (4), p.365-375</ispartof><rights>Japanese Society of Nephrology 2021</rights><rights>Japanese Society of Nephrology 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c520t-7984d4b4f898c7497ae6c9298ef97534ccc8a95065a0557a4a5972ec85a8d7c03</citedby><cites>FETCH-LOGICAL-c520t-7984d4b4f898c7497ae6c9298ef97534ccc8a95065a0557a4a5972ec85a8d7c03</cites><orcidid>0000-0002-0786-3197</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10157-020-02007-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10157-020-02007-2$$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/33409761$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamada, Shohei</creatorcontrib><creatorcontrib>Tanabe, Jun</creatorcontrib><creatorcontrib>Ogura, Yuji</creatorcontrib><creatorcontrib>Nagai, Yoshio</creatorcontrib><creatorcontrib>Sugaya, Takeshi</creatorcontrib><creatorcontrib>Ohata, Keiichi</creatorcontrib><creatorcontrib>Natsuki, Yasunori</creatorcontrib><creatorcontrib>Ichikawa, Daisuke</creatorcontrib><creatorcontrib>Watanabe, Shiika</creatorcontrib><creatorcontrib>Inoue, Kazuho</creatorcontrib><creatorcontrib>Hoshino, Seiko</creatorcontrib><creatorcontrib>Kimura, Kenjiro</creatorcontrib><creatorcontrib>Shibagaki, Yugo</creatorcontrib><creatorcontrib>Kamijo-Ikemori, Atsuko</creatorcontrib><title>Renoprotective effect of GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease in spontaneously diabetic Torii fatty rats</title><title>Clinical and experimental nephrology</title><addtitle>Clin Exp Nephrol</addtitle><addtitle>Clin Exp Nephrol</addtitle><description>Background
The aim of this study is to investigate the renoprotective effect of the GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease (DKD) using an animal model of type 2 diabetes with several metabolic disorders.
Methods
Male 8-week-old spontaneously diabetic Torii (SDT) fatty rats (
n
= 19) were randomly assigned to three groups. The liraglutide group (
n
= 6) was injected subcutaneously with liraglutide. Another treatment group (
n
= 6) received subcutaneous insulin against hyperglycemia and hydralazine against hypertension for matching blood glucose levels and blood pressure with the liraglutide group. The control groups of SDT fatty (
n
= 7) and non-diabetic Sprague–Dawley rats (
n
= 7) were injected only with a vehicle.
Results
The control group of SDT fatty rats exhibited hyperglycemia, obesity, hypertension, hyperlipidemia, glomerular sclerosis, and tubulointerstitial injury with high urinary albumin and L-FABP levels. Liraglutide treatment reduced body weight, food intake, blood glucose and blood pressure levels, as well as ameliorated renal pathologic findings with lower urinary albumin and L-FABP levels. Liraglutide increased expressions of phosphorylated (p)-eNOS and p-AMPK in glomeruli, downregulated renal expression of p-mTOR, and increased renal expressions of LC3B-II, suggesting activation of autophagy. However, these effects were not caused by the treatments with insulin and hydralazine, despite comparable levels of hyperglycemia and hypertension to those achieved with liraglutide treatment.
Conclusions
Liraglutide may exert a renoprotective effect via prevention of glomerular endothelial abnormality and preservation of autophagy in early-phase DKD, independent of blood glucose, and blood pressure levels.</description><subject>Agonists</subject><subject>Albumin</subject><subject>Albuminuria - physiopathology</subject><subject>Albuminuria - prevention & control</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antidiabetics</subject><subject>Autophagy</subject><subject>Autophagy - drug effects</subject><subject>Biomarkers - blood</subject><subject>Blood glucose</subject><subject>Blood Glucose - drug effects</subject><subject>Blood Glucose - metabolism</subject><subject>Blood pressure</subject><subject>Blood Pressure - drug effects</subject><subject>Body weight</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diabetes Mellitus, Type 2 - physiopathology</subject><subject>Diabetic Nephropathies - metabolism</subject><subject>Diabetic Nephropathies - pathology</subject><subject>Diabetic Nephropathies - physiopathology</subject><subject>Diabetic Nephropathies - prevention & control</subject><subject>Diabetic nephropathy</subject><subject>Disease Models, Animal</subject><subject>Fatty acid-binding protein</subject><subject>Food intake</subject><subject>GLP-1 receptor agonists</subject><subject>Glucagon-Like Peptide-1 Receptor - agonists</subject><subject>Glucagon-Like Peptide-1 Receptor - metabolism</subject><subject>Glucose</subject><subject>Hyperglycemia</subject><subject>Hyperlipidemia</subject><subject>Hypertension</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Incretins - pharmacology</subject><subject>Insulin</subject><subject>Kidney - drug effects</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>Kidney - physiopathology</subject><subject>Kidney diseases</subject><subject>Liraglutide - pharmacology</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic disorders</subject><subject>Nephrology</subject><subject>Original Article</subject><subject>Phagocytosis</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Sclerosis</subject><subject>Signal Transduction</subject><subject>TOR protein</subject><subject>Urology</subject><issn>1342-1751</issn><issn>1437-7799</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kcFu1DAQhiMEoqXwAhyQJS4cahg7dhwfUVVapJWoqnK2vM5kccnGwXYq5Sn6ynhJaSUOHKwZj7_5PfZfVW8ZfGQA6lNiwKSiwOGwQFH-rDpmolZUKa2fl7wWnDIl2VH1KqVbAGi11C-ro7oWoFXDjqv7axzDFENGl_0dEuz7kpHQk4vNFWUkosMph0jsLow-5VMy-Gh3w5x9h6fEjwRtHBY6_bAJSeftFrN35KfvRlzKPuGhXrA0hTHbEcOchuUJvAnRe9LbnBcSbU6vqxe9HRK-eYgn1fcv5zdnl3Tz7eLr2ecNdZJDpkq3ohNb0be6dUpoZbFxmusWe61kLZxzrdUSGmlBSmWFlVpxdK20bacc1CfVh1W3vP3XjCmbvU8Oh2Ed0XBRvodraHRB3_-D3oY5jmU6wyWwpmG1bgrFV8rFkFLE3kzR721cDANzsMusdplilfljl-Gl6d2D9LzdY_fY8tefAtQrkMrRuMP4dPd_ZH8D-QuhFQ</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Yamada, Shohei</creator><creator>Tanabe, Jun</creator><creator>Ogura, Yuji</creator><creator>Nagai, Yoshio</creator><creator>Sugaya, Takeshi</creator><creator>Ohata, Keiichi</creator><creator>Natsuki, Yasunori</creator><creator>Ichikawa, Daisuke</creator><creator>Watanabe, Shiika</creator><creator>Inoue, Kazuho</creator><creator>Hoshino, Seiko</creator><creator>Kimura, Kenjiro</creator><creator>Shibagaki, Yugo</creator><creator>Kamijo-Ikemori, Atsuko</creator><general>Springer 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>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0786-3197</orcidid></search><sort><creationdate>20210401</creationdate><title>Renoprotective effect of GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease in spontaneously diabetic Torii fatty rats</title><author>Yamada, Shohei ; Tanabe, Jun ; Ogura, Yuji ; Nagai, Yoshio ; Sugaya, Takeshi ; Ohata, Keiichi ; Natsuki, Yasunori ; Ichikawa, Daisuke ; Watanabe, Shiika ; Inoue, Kazuho ; Hoshino, Seiko ; Kimura, Kenjiro ; Shibagaki, Yugo ; Kamijo-Ikemori, Atsuko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c520t-7984d4b4f898c7497ae6c9298ef97534ccc8a95065a0557a4a5972ec85a8d7c03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Agonists</topic><topic>Albumin</topic><topic>Albuminuria - physiopathology</topic><topic>Albuminuria - prevention & control</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antidiabetics</topic><topic>Autophagy</topic><topic>Autophagy - drug effects</topic><topic>Biomarkers - blood</topic><topic>Blood glucose</topic><topic>Blood Glucose - drug effects</topic><topic>Blood Glucose - metabolism</topic><topic>Blood pressure</topic><topic>Blood Pressure - drug effects</topic><topic>Body weight</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diabetes Mellitus, Type 2 - physiopathology</topic><topic>Diabetic Nephropathies - metabolism</topic><topic>Diabetic Nephropathies - pathology</topic><topic>Diabetic Nephropathies - physiopathology</topic><topic>Diabetic Nephropathies - prevention & control</topic><topic>Diabetic nephropathy</topic><topic>Disease Models, Animal</topic><topic>Fatty acid-binding protein</topic><topic>Food intake</topic><topic>GLP-1 receptor agonists</topic><topic>Glucagon-Like Peptide-1 Receptor - agonists</topic><topic>Glucagon-Like Peptide-1 Receptor - metabolism</topic><topic>Glucose</topic><topic>Hyperglycemia</topic><topic>Hyperlipidemia</topic><topic>Hypertension</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Incretins - pharmacology</topic><topic>Insulin</topic><topic>Kidney - drug effects</topic><topic>Kidney - metabolism</topic><topic>Kidney - pathology</topic><topic>Kidney - physiopathology</topic><topic>Kidney diseases</topic><topic>Liraglutide - pharmacology</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolic disorders</topic><topic>Nephrology</topic><topic>Original Article</topic><topic>Phagocytosis</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Sclerosis</topic><topic>Signal Transduction</topic><topic>TOR protein</topic><topic>Urology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamada, Shohei</creatorcontrib><creatorcontrib>Tanabe, Jun</creatorcontrib><creatorcontrib>Ogura, Yuji</creatorcontrib><creatorcontrib>Nagai, Yoshio</creatorcontrib><creatorcontrib>Sugaya, Takeshi</creatorcontrib><creatorcontrib>Ohata, Keiichi</creatorcontrib><creatorcontrib>Natsuki, Yasunori</creatorcontrib><creatorcontrib>Ichikawa, Daisuke</creatorcontrib><creatorcontrib>Watanabe, Shiika</creatorcontrib><creatorcontrib>Inoue, Kazuho</creatorcontrib><creatorcontrib>Hoshino, Seiko</creatorcontrib><creatorcontrib>Kimura, Kenjiro</creatorcontrib><creatorcontrib>Shibagaki, Yugo</creatorcontrib><creatorcontrib>Kamijo-Ikemori, Atsuko</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>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical and experimental nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamada, Shohei</au><au>Tanabe, Jun</au><au>Ogura, Yuji</au><au>Nagai, Yoshio</au><au>Sugaya, Takeshi</au><au>Ohata, Keiichi</au><au>Natsuki, Yasunori</au><au>Ichikawa, Daisuke</au><au>Watanabe, Shiika</au><au>Inoue, Kazuho</au><au>Hoshino, Seiko</au><au>Kimura, Kenjiro</au><au>Shibagaki, Yugo</au><au>Kamijo-Ikemori, Atsuko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Renoprotective effect of GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease in spontaneously diabetic Torii fatty rats</atitle><jtitle>Clinical and experimental nephrology</jtitle><stitle>Clin Exp Nephrol</stitle><addtitle>Clin Exp Nephrol</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>25</volume><issue>4</issue><spage>365</spage><epage>375</epage><pages>365-375</pages><issn>1342-1751</issn><eissn>1437-7799</eissn><abstract>Background
The aim of this study is to investigate the renoprotective effect of the GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease (DKD) using an animal model of type 2 diabetes with several metabolic disorders.
Methods
Male 8-week-old spontaneously diabetic Torii (SDT) fatty rats (
n
= 19) were randomly assigned to three groups. The liraglutide group (
n
= 6) was injected subcutaneously with liraglutide. Another treatment group (
n
= 6) received subcutaneous insulin against hyperglycemia and hydralazine against hypertension for matching blood glucose levels and blood pressure with the liraglutide group. The control groups of SDT fatty (
n
= 7) and non-diabetic Sprague–Dawley rats (
n
= 7) were injected only with a vehicle.
Results
The control group of SDT fatty rats exhibited hyperglycemia, obesity, hypertension, hyperlipidemia, glomerular sclerosis, and tubulointerstitial injury with high urinary albumin and L-FABP levels. Liraglutide treatment reduced body weight, food intake, blood glucose and blood pressure levels, as well as ameliorated renal pathologic findings with lower urinary albumin and L-FABP levels. Liraglutide increased expressions of phosphorylated (p)-eNOS and p-AMPK in glomeruli, downregulated renal expression of p-mTOR, and increased renal expressions of LC3B-II, suggesting activation of autophagy. However, these effects were not caused by the treatments with insulin and hydralazine, despite comparable levels of hyperglycemia and hypertension to those achieved with liraglutide treatment.
Conclusions
Liraglutide may exert a renoprotective effect via prevention of glomerular endothelial abnormality and preservation of autophagy in early-phase DKD, independent of blood glucose, and blood pressure levels.</abstract><cop>Singapore</cop><pub>Springer Singapore</pub><pmid>33409761</pmid><doi>10.1007/s10157-020-02007-2</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-0786-3197</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1342-1751 |
| ispartof | Clinical and experimental nephrology, 2021-04, Vol.25 (4), p.365-375 |
| issn | 1342-1751 1437-7799 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2476129069 |
| source | MEDLINE; SpringerLink Journals |
| subjects | Agonists Albumin Albuminuria - physiopathology Albuminuria - prevention & control Animal models Animals Antidiabetics Autophagy Autophagy - drug effects Biomarkers - blood Blood glucose Blood Glucose - drug effects Blood Glucose - metabolism Blood pressure Blood Pressure - drug effects Body weight Diabetes Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - physiopathology Diabetic Nephropathies - metabolism Diabetic Nephropathies - pathology Diabetic Nephropathies - physiopathology Diabetic Nephropathies - prevention & control Diabetic nephropathy Disease Models, Animal Fatty acid-binding protein Food intake GLP-1 receptor agonists Glucagon-Like Peptide-1 Receptor - agonists Glucagon-Like Peptide-1 Receptor - metabolism Glucose Hyperglycemia Hyperlipidemia Hypertension Hypoglycemic Agents - pharmacology Incretins - pharmacology Insulin Kidney - drug effects Kidney - metabolism Kidney - pathology Kidney - physiopathology Kidney diseases Liraglutide - pharmacology Male Medicine Medicine & Public Health Metabolic disorders Nephrology Original Article Phagocytosis Rats Rats, Inbred Strains Sclerosis Signal Transduction TOR protein Urology |
| title | Renoprotective effect of GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease in spontaneously diabetic Torii fatty rats |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T10%3A42%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Renoprotective%20effect%20of%20GLP-1%20receptor%20agonist,%20liraglutide,%20in%20early-phase%20diabetic%20kidney%20disease%20in%20spontaneously%20diabetic%20Torii%20fatty%20rats&rft.jtitle=Clinical%20and%20experimental%20nephrology&rft.au=Yamada,%20Shohei&rft.date=2021-04-01&rft.volume=25&rft.issue=4&rft.spage=365&rft.epage=375&rft.pages=365-375&rft.issn=1342-1751&rft.eissn=1437-7799&rft_id=info:doi/10.1007/s10157-020-02007-2&rft_dat=%3Cproquest_cross%3E2476129069%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2501661396&rft_id=info:pmid/33409761&rfr_iscdi=true |