Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes
Aims/hypothesis Glucagon-like peptide-1 (GLP-1) has various extra-pancreatic actions, in addition to its enhancement of insulin secretion from pancreatic beta cells. The GLP-1 receptor is produced in kidney tissue. However, the direct effect of GLP-1 on diabetic nephropathy remains unclear. Here we...
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| Veröffentlicht in: | Diabetologia 2011-04, Vol.54 (4), p.965-978 |
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| creator | Kodera, R Shikata, K Kataoka, H. U Takatsuka, T Miyamoto, S Sasaki, M Kajitani, N Nishishita, S Sarai, K Hirota, D Sato, C Ogawa, D Makino, H |
| description | Aims/hypothesis Glucagon-like peptide-1 (GLP-1) has various extra-pancreatic actions, in addition to its enhancement of insulin secretion from pancreatic beta cells. The GLP-1 receptor is produced in kidney tissue. However, the direct effect of GLP-1 on diabetic nephropathy remains unclear. Here we demonstrate that a GLP-1 receptor agonist, exendin-4, exerts renoprotective effects through its anti-inflammatory action via the GLP-1 receptor without lowering blood glucose. Methods We administered exendin-4 at 10 μg/kg body weight daily for 8 weeks to a streptozotocin-induced rat model of type 1 diabetes and evaluated their urinary albumin excretion, metabolic data, histology and morphometry. We also examined the direct effects of exendin-4 on glomerular endothelial cells and macrophages in vitro. Results Exendin-4 ameliorated albuminuria, glomerular hyperfiltration, glomerular hypertrophy and mesangial matrix expansion in the diabetic rats without changing blood pressure or body weight. Exendin-4 also prevented macrophage infiltration, and decreased protein levels of intercellular adhesion molecule-1 (ICAM-1) and type IV collagen, as well as decreasing oxidative stress and nuclear factor-κB activation in kidney tissue. In addition, we found that the GLP-1 receptor was produced on monocytes/macrophages and glomerular endothelial cells. We demonstrated that in vitro exendin-4 acted directly on the GLP-1 receptor, and attenuated release of pro-inflammatory cytokines from macrophages and ICAM-1 production on glomerular endothelial cells. Conclusions/interpretation These results indicate that GLP-1 receptor agonists may prevent disease progression in the early stage of diabetic nephropathy through direct effects on the GLP-1 receptor in kidney tissue. |
| doi_str_mv | 10.1007/s00125-010-2028-x |
| format | Article |
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U ; Takatsuka, T ; Miyamoto, S ; Sasaki, M ; Kajitani, N ; Nishishita, S ; Sarai, K ; Hirota, D ; Sato, C ; Ogawa, D ; Makino, H</creator><creatorcontrib>Kodera, R ; Shikata, K ; Kataoka, H. U ; Takatsuka, T ; Miyamoto, S ; Sasaki, M ; Kajitani, N ; Nishishita, S ; Sarai, K ; Hirota, D ; Sato, C ; Ogawa, D ; Makino, H</creatorcontrib><description>Aims/hypothesis Glucagon-like peptide-1 (GLP-1) has various extra-pancreatic actions, in addition to its enhancement of insulin secretion from pancreatic beta cells. The GLP-1 receptor is produced in kidney tissue. However, the direct effect of GLP-1 on diabetic nephropathy remains unclear. Here we demonstrate that a GLP-1 receptor agonist, exendin-4, exerts renoprotective effects through its anti-inflammatory action via the GLP-1 receptor without lowering blood glucose. Methods We administered exendin-4 at 10 μg/kg body weight daily for 8 weeks to a streptozotocin-induced rat model of type 1 diabetes and evaluated their urinary albumin excretion, metabolic data, histology and morphometry. We also examined the direct effects of exendin-4 on glomerular endothelial cells and macrophages in vitro. Results Exendin-4 ameliorated albuminuria, glomerular hyperfiltration, glomerular hypertrophy and mesangial matrix expansion in the diabetic rats without changing blood pressure or body weight. Exendin-4 also prevented macrophage infiltration, and decreased protein levels of intercellular adhesion molecule-1 (ICAM-1) and type IV collagen, as well as decreasing oxidative stress and nuclear factor-κB activation in kidney tissue. In addition, we found that the GLP-1 receptor was produced on monocytes/macrophages and glomerular endothelial cells. We demonstrated that in vitro exendin-4 acted directly on the GLP-1 receptor, and attenuated release of pro-inflammatory cytokines from macrophages and ICAM-1 production on glomerular endothelial cells. Conclusions/interpretation These results indicate that GLP-1 receptor agonists may prevent disease progression in the early stage of diabetic nephropathy through direct effects on the GLP-1 receptor in kidney tissue.</description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-010-2028-x</identifier><identifier>PMID: 21253697</identifier><language>eng</language><publisher>Berlin/Heidelberg: Berlin/Heidelberg : Springer-Verlag</publisher><subject>Animals ; anti-inflammatory activity ; Associated diseases and complications ; Biological and medical sciences ; Blood Glucose - drug effects ; Blotting, Western ; Cell Line ; Cell Line, Tumor ; Collagen Type IV - metabolism ; Dentistry ; Diabetes ; Diabetes Mellitus, Type 1 - drug therapy ; Diabetes. Impaired glucose tolerance ; Diabetic Nephropathies - prevention & control ; Diabetic nephropathy ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Exendin-4 ; Fluorescent Antibody Technique ; Glomerular endothelial cells ; GLP-1 receptor agonist ; Glucagon ; Glucagon-Like Peptide-1 Receptor ; Glucose ; Human Physiology ; Humans ; Hypertension ; Hypothalamus ; Injuries of the urinary system. Foreign bodies. Diseases due to physical agents ; Intercellular adhesion molecule-1 ; Intercellular Adhesion Molecule-1 - metabolism ; Internal Medicine ; Kidneys ; Kinases ; Macrophage ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Metabolism ; Nephrology. Urinary tract diseases ; NF-kappa B - metabolism ; Nuclear factor-κB ; Oxidative stress ; Peptides ; Peptides - pharmacology ; Peptides - therapeutic use ; Pharmaceutical sciences ; Rats ; Rats, Sprague-Dawley ; Receptors, Glucagon - agonists ; Receptors, Glucagon - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Traumas. Diseases due to physical agents ; Tumor Necrosis Factor-alpha - pharmacology ; Type 1 diabetic rats ; Urinary system involvement in other diseases. 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U</creatorcontrib><creatorcontrib>Takatsuka, T</creatorcontrib><creatorcontrib>Miyamoto, S</creatorcontrib><creatorcontrib>Sasaki, M</creatorcontrib><creatorcontrib>Kajitani, N</creatorcontrib><creatorcontrib>Nishishita, S</creatorcontrib><creatorcontrib>Sarai, K</creatorcontrib><creatorcontrib>Hirota, D</creatorcontrib><creatorcontrib>Sato, C</creatorcontrib><creatorcontrib>Ogawa, D</creatorcontrib><creatorcontrib>Makino, H</creatorcontrib><title>Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><addtitle>Diabetologia</addtitle><description>Aims/hypothesis Glucagon-like peptide-1 (GLP-1) has various extra-pancreatic actions, in addition to its enhancement of insulin secretion from pancreatic beta cells. The GLP-1 receptor is produced in kidney tissue. However, the direct effect of GLP-1 on diabetic nephropathy remains unclear. Here we demonstrate that a GLP-1 receptor agonist, exendin-4, exerts renoprotective effects through its anti-inflammatory action via the GLP-1 receptor without lowering blood glucose. Methods We administered exendin-4 at 10 μg/kg body weight daily for 8 weeks to a streptozotocin-induced rat model of type 1 diabetes and evaluated their urinary albumin excretion, metabolic data, histology and morphometry. We also examined the direct effects of exendin-4 on glomerular endothelial cells and macrophages in vitro. Results Exendin-4 ameliorated albuminuria, glomerular hyperfiltration, glomerular hypertrophy and mesangial matrix expansion in the diabetic rats without changing blood pressure or body weight. Exendin-4 also prevented macrophage infiltration, and decreased protein levels of intercellular adhesion molecule-1 (ICAM-1) and type IV collagen, as well as decreasing oxidative stress and nuclear factor-κB activation in kidney tissue. In addition, we found that the GLP-1 receptor was produced on monocytes/macrophages and glomerular endothelial cells. We demonstrated that in vitro exendin-4 acted directly on the GLP-1 receptor, and attenuated release of pro-inflammatory cytokines from macrophages and ICAM-1 production on glomerular endothelial cells. Conclusions/interpretation These results indicate that GLP-1 receptor agonists may prevent disease progression in the early stage of diabetic nephropathy through direct effects on the GLP-1 receptor in kidney tissue.</description><subject>Animals</subject><subject>anti-inflammatory activity</subject><subject>Associated diseases and complications</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - drug effects</subject><subject>Blotting, Western</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Collagen Type IV - metabolism</subject><subject>Dentistry</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Type 1 - drug therapy</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Diabetic Nephropathies - prevention & control</subject><subject>Diabetic nephropathy</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Exendin-4</subject><subject>Fluorescent Antibody Technique</subject><subject>Glomerular endothelial cells</subject><subject>GLP-1 receptor agonist</subject><subject>Glucagon</subject><subject>Glucagon-Like Peptide-1 Receptor</subject><subject>Glucose</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypothalamus</subject><subject>Injuries of the urinary system. Foreign bodies. Diseases due to physical agents</subject><subject>Intercellular adhesion molecule-1</subject><subject>Intercellular Adhesion Molecule-1 - metabolism</subject><subject>Internal Medicine</subject><subject>Kidneys</subject><subject>Kinases</subject><subject>Macrophage</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolic Diseases</subject><subject>Metabolism</subject><subject>Nephrology. Urinary tract diseases</subject><subject>NF-kappa B - metabolism</subject><subject>Nuclear factor-κB</subject><subject>Oxidative stress</subject><subject>Peptides</subject><subject>Peptides - pharmacology</subject><subject>Peptides - therapeutic use</subject><subject>Pharmaceutical sciences</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Glucagon - agonists</subject><subject>Receptors, Glucagon - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Traumas. Diseases due to physical agents</subject><subject>Tumor Necrosis Factor-alpha - pharmacology</subject><subject>Type 1 diabetic rats</subject><subject>Urinary system involvement in other diseases. 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U ; Takatsuka, T ; Miyamoto, S ; Sasaki, M ; Kajitani, N ; Nishishita, S ; Sarai, K ; Hirota, D ; Sato, C ; Ogawa, D ; Makino, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c533t-4d4d95a2d02c37273c6ae1eee7587ceff26c5d726cc9a82e31ca63b7884834473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>anti-inflammatory activity</topic><topic>Associated diseases and complications</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - drug effects</topic><topic>Blotting, Western</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Collagen Type IV - metabolism</topic><topic>Dentistry</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Type 1 - drug therapy</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Diabetic Nephropathies - prevention & control</topic><topic>Diabetic nephropathy</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Exendin-4</topic><topic>Fluorescent Antibody Technique</topic><topic>Glomerular endothelial cells</topic><topic>GLP-1 receptor agonist</topic><topic>Glucagon</topic><topic>Glucagon-Like Peptide-1 Receptor</topic><topic>Glucose</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypothalamus</topic><topic>Injuries of the urinary system. Foreign bodies. 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Diseases due to physical agents</topic><topic>Tumor Necrosis Factor-alpha - pharmacology</topic><topic>Type 1 diabetic rats</topic><topic>Urinary system involvement in other diseases. Miscellaneous</topic><topic>Venoms - pharmacology</topic><topic>Venoms - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kodera, R</creatorcontrib><creatorcontrib>Shikata, K</creatorcontrib><creatorcontrib>Kataoka, H. 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U</au><au>Takatsuka, T</au><au>Miyamoto, S</au><au>Sasaki, M</au><au>Kajitani, N</au><au>Nishishita, S</au><au>Sarai, K</au><au>Hirota, D</au><au>Sato, C</au><au>Ogawa, D</au><au>Makino, H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes</atitle><jtitle>Diabetologia</jtitle><stitle>Diabetologia</stitle><addtitle>Diabetologia</addtitle><date>2011-04-01</date><risdate>2011</risdate><volume>54</volume><issue>4</issue><spage>965</spage><epage>978</epage><pages>965-978</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract>Aims/hypothesis Glucagon-like peptide-1 (GLP-1) has various extra-pancreatic actions, in addition to its enhancement of insulin secretion from pancreatic beta cells. The GLP-1 receptor is produced in kidney tissue. However, the direct effect of GLP-1 on diabetic nephropathy remains unclear. Here we demonstrate that a GLP-1 receptor agonist, exendin-4, exerts renoprotective effects through its anti-inflammatory action via the GLP-1 receptor without lowering blood glucose. Methods We administered exendin-4 at 10 μg/kg body weight daily for 8 weeks to a streptozotocin-induced rat model of type 1 diabetes and evaluated their urinary albumin excretion, metabolic data, histology and morphometry. We also examined the direct effects of exendin-4 on glomerular endothelial cells and macrophages in vitro. Results Exendin-4 ameliorated albuminuria, glomerular hyperfiltration, glomerular hypertrophy and mesangial matrix expansion in the diabetic rats without changing blood pressure or body weight. Exendin-4 also prevented macrophage infiltration, and decreased protein levels of intercellular adhesion molecule-1 (ICAM-1) and type IV collagen, as well as decreasing oxidative stress and nuclear factor-κB activation in kidney tissue. In addition, we found that the GLP-1 receptor was produced on monocytes/macrophages and glomerular endothelial cells. We demonstrated that in vitro exendin-4 acted directly on the GLP-1 receptor, and attenuated release of pro-inflammatory cytokines from macrophages and ICAM-1 production on glomerular endothelial cells. Conclusions/interpretation These results indicate that GLP-1 receptor agonists may prevent disease progression in the early stage of diabetic nephropathy through direct effects on the GLP-1 receptor in kidney tissue.</abstract><cop>Berlin/Heidelberg</cop><pub>Berlin/Heidelberg : Springer-Verlag</pub><pmid>21253697</pmid><doi>10.1007/s00125-010-2028-x</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals anti-inflammatory activity Associated diseases and complications Biological and medical sciences Blood Glucose - drug effects Blotting, Western Cell Line Cell Line, Tumor Collagen Type IV - metabolism Dentistry Diabetes Diabetes Mellitus, Type 1 - drug therapy Diabetes. Impaired glucose tolerance Diabetic Nephropathies - prevention & control Diabetic nephropathy Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Exendin-4 Fluorescent Antibody Technique Glomerular endothelial cells GLP-1 receptor agonist Glucagon Glucagon-Like Peptide-1 Receptor Glucose Human Physiology Humans Hypertension Hypothalamus Injuries of the urinary system. Foreign bodies. Diseases due to physical agents Intercellular adhesion molecule-1 Intercellular Adhesion Molecule-1 - metabolism Internal Medicine Kidneys Kinases Macrophage Male Medical sciences Medicine Medicine & Public Health Metabolic Diseases Metabolism Nephrology. Urinary tract diseases NF-kappa B - metabolism Nuclear factor-κB Oxidative stress Peptides Peptides - pharmacology Peptides - therapeutic use Pharmaceutical sciences Rats Rats, Sprague-Dawley Receptors, Glucagon - agonists Receptors, Glucagon - metabolism Reverse Transcriptase Polymerase Chain Reaction Traumas. Diseases due to physical agents Tumor Necrosis Factor-alpha - pharmacology Type 1 diabetic rats Urinary system involvement in other diseases. Miscellaneous Venoms - pharmacology Venoms - therapeutic use |
| title | Glucagon-like peptide-1 receptor agonist ameliorates renal injury through its anti-inflammatory action without lowering blood glucose level in a rat model of type 1 diabetes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T09%3A41%3A31IST&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=Glucagon-like%20peptide-1%20receptor%20agonist%20ameliorates%20renal%20injury%20through%20its%20anti-inflammatory%20action%20without%20lowering%20blood%20glucose%20level%20in%20a%20rat%20model%20of%20type%201%20diabetes&rft.jtitle=Diabetologia&rft.au=Kodera,%20R&rft.date=2011-04-01&rft.volume=54&rft.issue=4&rft.spage=965&rft.epage=978&rft.pages=965-978&rft.issn=0012-186X&rft.eissn=1432-0428&rft_id=info:doi/10.1007/s00125-010-2028-x&rft_dat=%3Cproquest_cross%3E2287979421%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=856180242&rft_id=info:pmid/21253697&rfr_iscdi=true |