Glomerular hyperfiltration with hyperglycemia in the spontaneously diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model
Glomerular hyperfiltration is observed in an early stage of kidney diseases including diabetic nephropathy. A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we invest...
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description | Glomerular hyperfiltration is observed in an early stage of kidney diseases including diabetic nephropathy. A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we investigated glomerular changes including glomerular filtration rate (GFR) and glomerular size in the Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model, and we also evaluated pharmacological effects of the sodium glucose cotransporter 2 inhibitor dapagliflozin on the renal lesions. Dapagliflozin was administered to SDT fatty rats from 5 to 17 weeks of age. Blood and urinary biochemical parameters were periodically measured. GFR was determined by transdermal GFR monitor at 16 weeks of age and histopathological analysis was performed at 17 weeks of age. SDT fatty rat developed severe hyperglycemia and exhibited pathophysiological abnormalities in the kidney, such as an increased GFR, glomerular hypertrophy and tissue lesions. Dapagliflozin achieved good glycemic control during the experimental period, inhibited the increase in GFR, and improved histopathological abnormalities in tubules. These results suggest that the SDT fatty rat is a useful model for analyzing the pathogenesis of diabetic nephropathy during its early stage and dapagliflozin improves not only hyperglycemia but also glomerular hyperfiltration and tubule lesions in SDT fatty rat. |
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A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we investigated glomerular changes including glomerular filtration rate (GFR) and glomerular size in the Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model, and we also evaluated pharmacological effects of the sodium glucose cotransporter 2 inhibitor dapagliflozin on the renal lesions. Dapagliflozin was administered to SDT fatty rats from 5 to 17 weeks of age. Blood and urinary biochemical parameters were periodically measured. GFR was determined by transdermal GFR monitor at 16 weeks of age and histopathological analysis was performed at 17 weeks of age. SDT fatty rat developed severe hyperglycemia and exhibited pathophysiological abnormalities in the kidney, such as an increased GFR, glomerular hypertrophy and tissue lesions. Dapagliflozin achieved good glycemic control during the experimental period, inhibited the increase in GFR, and improved histopathological abnormalities in tubules. These results suggest that the SDT fatty rat is a useful model for analyzing the pathogenesis of diabetic nephropathy during its early stage and dapagliflozin improves not only hyperglycemia but also glomerular hyperfiltration and tubule lesions in SDT fatty rat.</description><identifier>ISSN: 0862-8408</identifier><identifier>EISSN: 1802-9973</identifier><identifier>DOI: 10.33549/physiolres.934533</identifier><identifier>PMID: 33453716</identifier><language>eng</language><publisher>Czech Republic: Institute of Physiology</publisher><subject>Age ; Animals ; Benzhydryl Compounds - pharmacology ; Cholesterol ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Experimental - drug therapy ; Diabetes Mellitus, Experimental - genetics ; Diabetes Mellitus, Experimental - physiopathology ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - pathology ; Diabetes Mellitus, Type 2 - physiopathology ; Diabetic Nephropathies - drug therapy ; Diabetic Nephropathies - etiology ; Diabetic nephropathy ; Disease Models, Animal ; Food ; Glomerular Filtration Rate ; Glucose ; Glucosides - pharmacology ; Hyperglycemia ; Hyperglycemia - drug therapy ; Hyperglycemia - pathology ; Hypertrophy ; Kidney diseases ; Lesions ; Male ; Metabolism ; Nephropathy ; Obesity ; Obesity - complications ; Obesity - genetics ; Pathogenesis ; Rats ; Rats, Sprague-Dawley ; Sodium-glucose cotransporter ; Sodium-Glucose Transporter 2 Inhibitors - pharmacology ; Tubules</subject><ispartof>Physiological research, 2021-02, Vol.70 (1), p.45-54</ispartof><rights>Copyright Institute of Physiology 2021</rights><rights>2021 Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c397t-77933c0a6cb9648d8a4452107a65c2fc83ee02377fdaed5b7b555e5d630c19e93</citedby><cites>FETCH-LOGICAL-c397t-77933c0a6cb9648d8a4452107a65c2fc83ee02377fdaed5b7b555e5d630c19e93</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/PMC8820518/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820518/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33453716$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sano, R</creatorcontrib><creatorcontrib>Ishii, Y</creatorcontrib><creatorcontrib>Yamanaka, M</creatorcontrib><creatorcontrib>Yasui, Y</creatorcontrib><creatorcontrib>Kemmochi, Y</creatorcontrib><creatorcontrib>Kuroki, F</creatorcontrib><creatorcontrib>Sugimoto, M</creatorcontrib><creatorcontrib>Fukuda, S</creatorcontrib><creatorcontrib>Sasase, T</creatorcontrib><creatorcontrib>Miyajima, K</creatorcontrib><creatorcontrib>Nakae, D</creatorcontrib><creatorcontrib>Ohta, T</creatorcontrib><title>Glomerular hyperfiltration with hyperglycemia in the spontaneously diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model</title><title>Physiological research</title><addtitle>Physiol Res</addtitle><description>Glomerular hyperfiltration is observed in an early stage of kidney diseases including diabetic nephropathy. A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we investigated glomerular changes including glomerular filtration rate (GFR) and glomerular size in the Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model, and we also evaluated pharmacological effects of the sodium glucose cotransporter 2 inhibitor dapagliflozin on the renal lesions. Dapagliflozin was administered to SDT fatty rats from 5 to 17 weeks of age. Blood and urinary biochemical parameters were periodically measured. GFR was determined by transdermal GFR monitor at 16 weeks of age and histopathological analysis was performed at 17 weeks of age. SDT fatty rat developed severe hyperglycemia and exhibited pathophysiological abnormalities in the kidney, such as an increased GFR, glomerular hypertrophy and tissue lesions. Dapagliflozin achieved good glycemic control during the experimental period, inhibited the increase in GFR, and improved histopathological abnormalities in tubules. These results suggest that the SDT fatty rat is a useful model for analyzing the pathogenesis of diabetic nephropathy during its early stage and dapagliflozin improves not only hyperglycemia but also glomerular hyperfiltration and tubule lesions in SDT fatty rat.</description><subject>Age</subject><subject>Animals</subject><subject>Benzhydryl Compounds - pharmacology</subject><subject>Cholesterol</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Diabetes Mellitus, Experimental - genetics</subject><subject>Diabetes Mellitus, Experimental - physiopathology</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - pathology</subject><subject>Diabetes Mellitus, Type 2 - physiopathology</subject><subject>Diabetic Nephropathies - drug therapy</subject><subject>Diabetic Nephropathies - etiology</subject><subject>Diabetic nephropathy</subject><subject>Disease Models, Animal</subject><subject>Food</subject><subject>Glomerular Filtration Rate</subject><subject>Glucose</subject><subject>Glucosides - pharmacology</subject><subject>Hyperglycemia</subject><subject>Hyperglycemia - drug therapy</subject><subject>Hyperglycemia - pathology</subject><subject>Hypertrophy</subject><subject>Kidney diseases</subject><subject>Lesions</subject><subject>Male</subject><subject>Metabolism</subject><subject>Nephropathy</subject><subject>Obesity</subject><subject>Obesity - complications</subject><subject>Obesity - genetics</subject><subject>Pathogenesis</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Sodium-glucose cotransporter</subject><subject>Sodium-Glucose Transporter 2 Inhibitors - pharmacology</subject><subject>Tubules</subject><issn>0862-8408</issn><issn>1802-9973</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpVkc1u1TAQhS1ERS-FF2CBLLEBiRT_xLG9QUIFWqRKLLisLceZNK6cONgOKEvenJRbWroaaebMN2d0EHpBySnnotbv5mHNPoYE-VTzWnD-CO2oIqzSWvLHaEdUwypVE3WMnuZ8TQiTRPIn6JjfqCVtduj3eYgjpCXYhId1htT7UJItPk74ly_DoXkVVgejt9hPuAyA8xynYieISw4r7rxtoXiH9zF5j19_-7h_g3tbyoo30ltsJxxbyIDLxsLsXj_GDsIzdNTbkOH5bT1B3z9_2p9dVJdfz7-cfbisHNeyVFJqzh2xjWt1U6tO2boWjBJpG-FY7xQHIIxL2XcWOtHKVggBoms4cVSD5ifo_YE7L-0InYNp-zOYOfnRptVE683DyeQHcxV_GqUYEVRtgFe3gBR_LJCLuY5LmjbPhgnGqaRCkU3FDiqXYs4J-rsLlJi_sZn72Mwhtm3p5f_e7lb-5cT_AHXama0</recordid><startdate>20210201</startdate><enddate>20210201</enddate><creator>Sano, R</creator><creator>Ishii, Y</creator><creator>Yamanaka, M</creator><creator>Yasui, Y</creator><creator>Kemmochi, Y</creator><creator>Kuroki, F</creator><creator>Sugimoto, M</creator><creator>Fukuda, S</creator><creator>Sasase, T</creator><creator>Miyajima, K</creator><creator>Nakae, D</creator><creator>Ohta, T</creator><general>Institute of Physiology</general><general>Institute of Physiology of the Czech Academy of Sciences</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>4T-</scope><scope>4U-</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BYOGL</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20210201</creationdate><title>Glomerular hyperfiltration with hyperglycemia in the spontaneously diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model</title><author>Sano, R ; Ishii, Y ; Yamanaka, M ; Yasui, Y ; Kemmochi, Y ; Kuroki, F ; Sugimoto, M ; Fukuda, S ; Sasase, T ; Miyajima, K ; Nakae, D ; Ohta, T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c397t-77933c0a6cb9648d8a4452107a65c2fc83ee02377fdaed5b7b555e5d630c19e93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Age</topic><topic>Animals</topic><topic>Benzhydryl Compounds - pharmacology</topic><topic>Cholesterol</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Diabetes Mellitus, Experimental - genetics</topic><topic>Diabetes Mellitus, Experimental - physiopathology</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - pathology</topic><topic>Diabetes Mellitus, Type 2 - physiopathology</topic><topic>Diabetic Nephropathies - drug therapy</topic><topic>Diabetic Nephropathies - etiology</topic><topic>Diabetic nephropathy</topic><topic>Disease Models, Animal</topic><topic>Food</topic><topic>Glomerular Filtration Rate</topic><topic>Glucose</topic><topic>Glucosides - pharmacology</topic><topic>Hyperglycemia</topic><topic>Hyperglycemia - drug therapy</topic><topic>Hyperglycemia - pathology</topic><topic>Hypertrophy</topic><topic>Kidney diseases</topic><topic>Lesions</topic><topic>Male</topic><topic>Metabolism</topic><topic>Nephropathy</topic><topic>Obesity</topic><topic>Obesity - complications</topic><topic>Obesity - genetics</topic><topic>Pathogenesis</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Sodium-glucose cotransporter</topic><topic>Sodium-Glucose Transporter 2 Inhibitors - pharmacology</topic><topic>Tubules</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sano, R</creatorcontrib><creatorcontrib>Ishii, Y</creatorcontrib><creatorcontrib>Yamanaka, M</creatorcontrib><creatorcontrib>Yasui, Y</creatorcontrib><creatorcontrib>Kemmochi, Y</creatorcontrib><creatorcontrib>Kuroki, F</creatorcontrib><creatorcontrib>Sugimoto, M</creatorcontrib><creatorcontrib>Fukuda, S</creatorcontrib><creatorcontrib>Sasase, T</creatorcontrib><creatorcontrib>Miyajima, K</creatorcontrib><creatorcontrib>Nakae, D</creatorcontrib><creatorcontrib>Ohta, T</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>Docstoc</collection><collection>University Readers</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>East Europe, Central Europe Database</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</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>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Physiological research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sano, R</au><au>Ishii, Y</au><au>Yamanaka, M</au><au>Yasui, Y</au><au>Kemmochi, Y</au><au>Kuroki, F</au><au>Sugimoto, M</au><au>Fukuda, S</au><au>Sasase, T</au><au>Miyajima, K</au><au>Nakae, D</au><au>Ohta, T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glomerular hyperfiltration with hyperglycemia in the spontaneously diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model</atitle><jtitle>Physiological research</jtitle><addtitle>Physiol Res</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>70</volume><issue>1</issue><spage>45</spage><epage>54</epage><pages>45-54</pages><issn>0862-8408</issn><eissn>1802-9973</eissn><abstract>Glomerular hyperfiltration is observed in an early stage of kidney diseases including diabetic nephropathy. A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we investigated glomerular changes including glomerular filtration rate (GFR) and glomerular size in the Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model, and we also evaluated pharmacological effects of the sodium glucose cotransporter 2 inhibitor dapagliflozin on the renal lesions. Dapagliflozin was administered to SDT fatty rats from 5 to 17 weeks of age. Blood and urinary biochemical parameters were periodically measured. GFR was determined by transdermal GFR monitor at 16 weeks of age and histopathological analysis was performed at 17 weeks of age. SDT fatty rat developed severe hyperglycemia and exhibited pathophysiological abnormalities in the kidney, such as an increased GFR, glomerular hypertrophy and tissue lesions. Dapagliflozin achieved good glycemic control during the experimental period, inhibited the increase in GFR, and improved histopathological abnormalities in tubules. These results suggest that the SDT fatty rat is a useful model for analyzing the pathogenesis of diabetic nephropathy during its early stage and dapagliflozin improves not only hyperglycemia but also glomerular hyperfiltration and tubule lesions in SDT fatty rat.</abstract><cop>Czech Republic</cop><pub>Institute of Physiology</pub><pmid>33453716</pmid><doi>10.33549/physiolres.934533</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Age Animals Benzhydryl Compounds - pharmacology Cholesterol Diabetes Diabetes mellitus Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - genetics Diabetes Mellitus, Experimental - physiopathology Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - pathology Diabetes Mellitus, Type 2 - physiopathology Diabetic Nephropathies - drug therapy Diabetic Nephropathies - etiology Diabetic nephropathy Disease Models, Animal Food Glomerular Filtration Rate Glucose Glucosides - pharmacology Hyperglycemia Hyperglycemia - drug therapy Hyperglycemia - pathology Hypertrophy Kidney diseases Lesions Male Metabolism Nephropathy Obesity Obesity - complications Obesity - genetics Pathogenesis Rats Rats, Sprague-Dawley Sodium-glucose cotransporter Sodium-Glucose Transporter 2 Inhibitors - pharmacology Tubules |
title | Glomerular hyperfiltration with hyperglycemia in the spontaneously diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model |
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