Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin
Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protectiv...
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Veröffentlicht in: | Experimental diabetes research 2012-01, Vol.2012 (2012), p.1-9 |
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description | Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT) rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day) was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c), and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG) levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury. |
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Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT) rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day) was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c), and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG) levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.</description><identifier>ISSN: 1687-5214</identifier><identifier>EISSN: 1687-5303</identifier><identifier>DOI: 10.1155/2012/210821</identifier><identifier>PMID: 23056035</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Puplishing Corporation</publisher><subject>Albuminuria - etiology ; Albuminuria - prevention & control ; Animals ; Antioxidants - therapeutic use ; Apoptosis - drug effects ; Deoxyguanosine - analogs & derivatives ; Deoxyguanosine - metabolism ; Deoxyguanosine - urine ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes Mellitus, Type 2 - pathology ; Diabetic Nephropathies - prevention & control ; Disease Models, Animal ; DNA Fragmentation - drug effects ; Drug therapy ; Eye ; Health aspects ; Hypoglycemic Agents - therapeutic use ; Injuries ; Kidney - drug effects ; Kidney - metabolism ; Kidney - pathology ; Male ; Metformin ; Metformin - therapeutic use ; Microfilament Proteins - metabolism ; Oxidative Stress - drug effects ; Podocytes - drug effects ; Podocytes - metabolism ; Podocytes - pathology ; Random Allocation ; Rats ; Rats, Inbred Strains ; Rats, Sprague-Dawley ; Type 2 diabetes</subject><ispartof>Experimental diabetes research, 2012-01, Vol.2012 (2012), p.1-9</ispartof><rights>Copyright © 2012 Junghyun Kim et al.</rights><rights>COPYRIGHT 2012 John Wiley & Sons, Inc.</rights><rights>Copyright © 2012 Junghyun Kim et al. 2012</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c571t-ddd3cbca177c4ae33b33f21b7d93f5a08b313b6186589cd34333ed425078ad43</citedby><cites>FETCH-LOGICAL-c571t-ddd3cbca177c4ae33b33f21b7d93f5a08b313b6186589cd34333ed425078ad43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465985/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465985/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,27925,27926,53792,53794</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23056035$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Shimizu, Yoshio</contributor><creatorcontrib>Kim, Jin Sook</creatorcontrib><creatorcontrib>Kim, Chan-Sik</creatorcontrib><creatorcontrib>Sohn, Eunjin</creatorcontrib><creatorcontrib>Kim, Junghyun</creatorcontrib><title>Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin</title><title>Experimental diabetes research</title><addtitle>Exp Diabetes Res</addtitle><description>Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT) rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day) was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c), and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG) levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.</description><subject>Albuminuria - etiology</subject><subject>Albuminuria - prevention & control</subject><subject>Animals</subject><subject>Antioxidants - therapeutic use</subject><subject>Apoptosis - drug effects</subject><subject>Deoxyguanosine - analogs & derivatives</subject><subject>Deoxyguanosine - metabolism</subject><subject>Deoxyguanosine - urine</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diabetes Mellitus, Type 2 - pathology</subject><subject>Diabetic Nephropathies - prevention & control</subject><subject>Disease Models, Animal</subject><subject>DNA Fragmentation - drug effects</subject><subject>Drug therapy</subject><subject>Eye</subject><subject>Health aspects</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Injuries</subject><subject>Kidney - drug effects</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>Male</subject><subject>Metformin</subject><subject>Metformin - therapeutic use</subject><subject>Microfilament Proteins - metabolism</subject><subject>Oxidative Stress - drug effects</subject><subject>Podocytes - drug effects</subject><subject>Podocytes - metabolism</subject><subject>Podocytes - pathology</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><subject>Rats, Sprague-Dawley</subject><subject>Type 2 diabetes</subject><issn>1687-5214</issn><issn>1687-5303</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><recordid>eNqFkc1LJDEQxcPisn7tac8rgb0po0mq0525COLXDii6MveQTioa6U6G7tal_3sjvQ4rCFKHFJVfPV7yCPnB2SHnUh4JxsWR4EwJ_oVs8VJVMwkMNt56wYtNst33j4wVpZTqG9kUwGTJQG6RP3cYTUNvk0t2HJAu4uNTN9IQqaF3ZqDXyWFDk6fLcYVU0LNgahywp4ue3nb4jHFAR-uRXuPgU9eGuEu-etP0-P3fuUOWF-fL09-zq5vLxenJ1czKig8z5xzY2hpeVbYwCFADeMHrys3BS8NUDRzqkqtSqrl1UAAAukJIVinjCtghx5Ps6qlu0dlspDONXnWhNd2okwn6_U0MD_o-PWvInzBXMgv8mgTuTYM6RJ8yZtvQW30CXM2ZkCAydfgBlcthG2yK6EOev1s4mBZsl_q-Q7-2xJl-zUu_5qWnvDK99_8r1uxbQBnYn4CHEJ35Gz5R-znBmBH0Zg0XslCVghedWaSb</recordid><startdate>20120101</startdate><enddate>20120101</enddate><creator>Kim, Jin Sook</creator><creator>Kim, Chan-Sik</creator><creator>Sohn, Eunjin</creator><creator>Kim, Junghyun</creator><general>Hindawi Puplishing Corporation</general><general>Hindawi Publishing Corporation</general><general>John Wiley & Sons, Inc</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><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>5PM</scope></search><sort><creationdate>20120101</creationdate><title>Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin</title><author>Kim, Jin Sook ; Kim, Chan-Sik ; Sohn, Eunjin ; Kim, Junghyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c571t-ddd3cbca177c4ae33b33f21b7d93f5a08b313b6186589cd34333ed425078ad43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Albuminuria - etiology</topic><topic>Albuminuria - prevention & control</topic><topic>Animals</topic><topic>Antioxidants - therapeutic use</topic><topic>Apoptosis - drug effects</topic><topic>Deoxyguanosine - analogs & derivatives</topic><topic>Deoxyguanosine - metabolism</topic><topic>Deoxyguanosine - urine</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diabetes Mellitus, Type 2 - pathology</topic><topic>Diabetic Nephropathies - prevention & control</topic><topic>Disease Models, Animal</topic><topic>DNA Fragmentation - drug effects</topic><topic>Drug therapy</topic><topic>Eye</topic><topic>Health aspects</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Injuries</topic><topic>Kidney - drug effects</topic><topic>Kidney - metabolism</topic><topic>Kidney - pathology</topic><topic>Male</topic><topic>Metformin</topic><topic>Metformin - therapeutic use</topic><topic>Microfilament Proteins - metabolism</topic><topic>Oxidative Stress - drug effects</topic><topic>Podocytes - drug effects</topic><topic>Podocytes - metabolism</topic><topic>Podocytes - pathology</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><topic>Rats, Sprague-Dawley</topic><topic>Type 2 diabetes</topic><toplevel>online_resources</toplevel><creatorcontrib>Kim, Jin Sook</creatorcontrib><creatorcontrib>Kim, Chan-Sik</creatorcontrib><creatorcontrib>Sohn, Eunjin</creatorcontrib><creatorcontrib>Kim, Junghyun</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical Periodicals</collection><collection>معرفة - المحتوى العربي الأكاديمي المتكامل - e-Marefa Academic Complete</collection><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Experimental diabetes research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kim, Jin Sook</au><au>Kim, Chan-Sik</au><au>Sohn, Eunjin</au><au>Kim, Junghyun</au><au>Shimizu, Yoshio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin</atitle><jtitle>Experimental diabetes research</jtitle><addtitle>Exp Diabetes Res</addtitle><date>2012-01-01</date><risdate>2012</risdate><volume>2012</volume><issue>2012</issue><spage>1</spage><epage>9</epage><pages>1-9</pages><issn>1687-5214</issn><eissn>1687-5303</eissn><abstract>Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT) rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day) was given to SDT rats for 17 weeks. Blood glucose, glycated haemoglobin (HbA1c), and albuminuria were examined. Kidney histopathology, renal 8-hydroxydeoxyguanosine (8-OHdG) levels and apoptosis were examined. In 43-week-old SDT rats, severe hyperglycemia was developed, and albuminuria was markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, urinary and renal 8-OHdG levels were highly increased, and podocyte loss was shown through application of the TUNEL and synaptopodin staining. However, treatment of SDT rats with metformin restored all these renal changes. Our data suggested that diabetes-induced podocyte loss in diabetic nephropathy could be suppressed by the antidiabetes drug, metformin, through the repression of oxidative injury.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Puplishing Corporation</pub><pmid>23056035</pmid><doi>10.1155/2012/210821</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Albuminuria - etiology Albuminuria - prevention & control Animals Antioxidants - therapeutic use Apoptosis - drug effects Deoxyguanosine - analogs & derivatives Deoxyguanosine - metabolism Deoxyguanosine - urine Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - pathology Diabetic Nephropathies - prevention & control Disease Models, Animal DNA Fragmentation - drug effects Drug therapy Eye Health aspects Hypoglycemic Agents - therapeutic use Injuries Kidney - drug effects Kidney - metabolism Kidney - pathology Male Metformin Metformin - therapeutic use Microfilament Proteins - metabolism Oxidative Stress - drug effects Podocytes - drug effects Podocytes - metabolism Podocytes - pathology Random Allocation Rats Rats, Inbred Strains Rats, Sprague-Dawley Type 2 diabetes |
title | Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin |
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