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
Hauptverfasser: Kim, Jin Sook, Kim, Chan-Sik, Sohn, Eunjin, Kim, Junghyun
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container_title Experimental diabetes research
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creator Kim, Jin Sook
Kim, Chan-Sik
Sohn, Eunjin
Kim, Junghyun
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. 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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. 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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 &amp; 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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