Abstract 14444: Type 2 Diabetic Rat Model With Low Dose Streptozotocin and High Fat Diet: Characterizing Cardiorenal Function and Fibrosis in Diabetic Cardiomyopathy

IntroductionHigh dose streptozotocin (STZ) injection results in pancreatic destruction and a type 1 diabetic (T1DM) rat model. Low dose STZ with high fat diet may represent a type 2 diabetes (T2DM) insulin-resistance model, which would allow for greater translational investigation into cardiorenal c...

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Veröffentlicht in:Circulation (New York, N.Y.) N.Y.), 2018-11, Vol.138 (Suppl_1 Suppl 1), p.A14444-A14444
Hauptverfasser: Wan, Siu-Hin, Ameenuddin, Syed, Koehn, Madeline, May, Ronald, Chen, Horng H
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container_issue Suppl_1 Suppl 1
container_start_page A14444
container_title Circulation (New York, N.Y.)
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creator Wan, Siu-Hin
Ameenuddin, Syed
Koehn, Madeline
May, Ronald
Chen, Horng H
description IntroductionHigh dose streptozotocin (STZ) injection results in pancreatic destruction and a type 1 diabetic (T1DM) rat model. Low dose STZ with high fat diet may represent a type 2 diabetes (T2DM) insulin-resistance model, which would allow for greater translational investigation into cardiorenal complications of T2DM.PurposeThe objective is to establish and characterize cardiorenal function and fibrosis in a type 2 diabetes rat model.MethodsTen week old male Wistar rats were divided into three groupscontrol n=23, type 1 DM n=17 and type 2 DM n=11. Rats in the type 1 DM group were injected STZ at 65 mg/kg intraperitoneally and fed regular diet. Rats in T2DM were injected with two doses of STZ at 35 mg/kg within 24 hours and fed high fat diet. Rats in the control group were injected with citrate buffer (pH 5.0) and fed regular diet. Weights, blood glucose, and 24-hour urine collection were recorded. After 3 months, rats were anesthetized, blood and urine collected, and tissues harvested for histological analysis.ResultsDiabetes was confirmed in the T1DM and T2DM vs control group (plasma glucose 443±19 and 350±11 vs 114±4 mg/dL). However, blood glucose was lower in T2DM vs T1DM (p
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Low dose STZ with high fat diet may represent a type 2 diabetes (T2DM) insulin-resistance model, which would allow for greater translational investigation into cardiorenal complications of T2DM.PurposeThe objective is to establish and characterize cardiorenal function and fibrosis in a type 2 diabetes rat model.MethodsTen week old male Wistar rats were divided into three groupscontrol n=23, type 1 DM n=17 and type 2 DM n=11. Rats in the type 1 DM group were injected STZ at 65 mg/kg intraperitoneally and fed regular diet. Rats in T2DM were injected with two doses of STZ at 35 mg/kg within 24 hours and fed high fat diet. Rats in the control group were injected with citrate buffer (pH 5.0) and fed regular diet. Weights, blood glucose, and 24-hour urine collection were recorded. After 3 months, rats were anesthetized, blood and urine collected, and tissues harvested for histological analysis.ResultsDiabetes was confirmed in the T1DM and T2DM vs control group (plasma glucose 443±19 and 350±11 vs 114±4 mg/dL). However, blood glucose was lower in T2DM vs T1DM (p<0.01). Plasma insulin was not statistically different between the control and T2DM groups (0.67±0.08 and 0.30±0.05 ng/mL, p=0.97) but lower in the T1DM group (0.04±0.01 ng/mL, p<0.01). By picrosirius staining, LV interstitial, kidney cortex, and pancreas fibrosis were greater in the T2DM vs control group (2.75±0.27 vs 1.08±0.12% p<0.01; 7.97±0.53 vs 1.95±0.23% p<0.01; 5.47±0.37 vs 1.87±0.29%, p<0.01, respectively). There was greater 24 hour urine protein excretion in T1DM and T2DM vs control group (1.73±0.16 and 9.94±2.55 vs 0.78±0.10 mg/min, p<0.01). Plasma cGMP was higher in the T1DM and T2DM vs control group (10.15±1.05 and 8.85±1.21 vs 4.27±0.49 pmol/min, p<0.01).ConclusionsT2DM was successfully induced in a low dose streptozotocin high fat diet rat model, as confirmed by increased plasma glucose but preserved plasma insulin levels. Significant increases in fibrosis, urine protein, and plasma cGMP in the T2DM vs control group represent a viable rat model for investigation of cardiorenal complications of T2DM with non-insulin anti-glycemic agents.]]></description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><language>eng</language><publisher>by the American College of Cardiology Foundation and the American Heart Association, Inc</publisher><ispartof>Circulation (New York, N.Y.), 2018-11, Vol.138 (Suppl_1 Suppl 1), p.A14444-A14444</ispartof><rights>2018 by the American College of Cardiology Foundation and the American Heart Association, Inc.</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids></links><search><creatorcontrib>Wan, Siu-Hin</creatorcontrib><creatorcontrib>Ameenuddin, Syed</creatorcontrib><creatorcontrib>Koehn, Madeline</creatorcontrib><creatorcontrib>May, Ronald</creatorcontrib><creatorcontrib>Chen, Horng H</creatorcontrib><title>Abstract 14444: Type 2 Diabetic Rat Model With Low Dose Streptozotocin and High Fat Diet: Characterizing Cardiorenal Function and Fibrosis in Diabetic Cardiomyopathy</title><title>Circulation (New York, N.Y.)</title><description><![CDATA[IntroductionHigh dose streptozotocin (STZ) injection results in pancreatic destruction and a type 1 diabetic (T1DM) rat model. Low dose STZ with high fat diet may represent a type 2 diabetes (T2DM) insulin-resistance model, which would allow for greater translational investigation into cardiorenal complications of T2DM.PurposeThe objective is to establish and characterize cardiorenal function and fibrosis in a type 2 diabetes rat model.MethodsTen week old male Wistar rats were divided into three groupscontrol n=23, type 1 DM n=17 and type 2 DM n=11. Rats in the type 1 DM group were injected STZ at 65 mg/kg intraperitoneally and fed regular diet. Rats in T2DM were injected with two doses of STZ at 35 mg/kg within 24 hours and fed high fat diet. Rats in the control group were injected with citrate buffer (pH 5.0) and fed regular diet. Weights, blood glucose, and 24-hour urine collection were recorded. After 3 months, rats were anesthetized, blood and urine collected, and tissues harvested for histological analysis.ResultsDiabetes was confirmed in the T1DM and T2DM vs control group (plasma glucose 443±19 and 350±11 vs 114±4 mg/dL). However, blood glucose was lower in T2DM vs T1DM (p<0.01). Plasma insulin was not statistically different between the control and T2DM groups (0.67±0.08 and 0.30±0.05 ng/mL, p=0.97) but lower in the T1DM group (0.04±0.01 ng/mL, p<0.01). By picrosirius staining, LV interstitial, kidney cortex, and pancreas fibrosis were greater in the T2DM vs control group (2.75±0.27 vs 1.08±0.12% p<0.01; 7.97±0.53 vs 1.95±0.23% p<0.01; 5.47±0.37 vs 1.87±0.29%, p<0.01, respectively). There was greater 24 hour urine protein excretion in T1DM and T2DM vs control group (1.73±0.16 and 9.94±2.55 vs 0.78±0.10 mg/min, p<0.01). Plasma cGMP was higher in the T1DM and T2DM vs control group (10.15±1.05 and 8.85±1.21 vs 4.27±0.49 pmol/min, p<0.01).ConclusionsT2DM was successfully induced in a low dose streptozotocin high fat diet rat model, as confirmed by increased plasma glucose but preserved plasma insulin levels. Significant increases in fibrosis, urine protein, and plasma cGMP in the T2DM vs control group represent a viable rat model for investigation of cardiorenal complications of T2DM with non-insulin anti-glycemic agents.]]></description><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNqdT0tOwzAUtBCVCJ87vAtEsvMl3aGEqAvYQCWWlZO49QMTR_arovQ-3BOjIg7AbEYjzUdzwSKRJ1mc5Wl1ySLOeRWXaZJcsWvv34Ms0jKP2NdD58nJnkBkAWvYLpOCBBqUnSLs4UUSPNtBGXhD0vBkZ2isV_BKTk1kT5ZsjyPIcYANHjS0wd-gojXUWv4UK4cnHA9QSzegdWqUBtrj2BPac6zFzlmPHkLN3-zZ_bnYSZJebtlqL41Xd798w7L2cVtv4tmaMOA_zHFWbqeVNKR34RxPuSjjhIt7IXghYi6qvEj_GfsGv9hlFg</recordid><startdate>20181106</startdate><enddate>20181106</enddate><creator>Wan, Siu-Hin</creator><creator>Ameenuddin, Syed</creator><creator>Koehn, Madeline</creator><creator>May, Ronald</creator><creator>Chen, Horng H</creator><general>by the American College of Cardiology Foundation and the American Heart Association, Inc</general><scope/></search><sort><creationdate>20181106</creationdate><title>Abstract 14444: Type 2 Diabetic Rat Model With Low Dose Streptozotocin and High Fat Diet: Characterizing Cardiorenal Function and Fibrosis in Diabetic Cardiomyopathy</title><author>Wan, Siu-Hin ; Ameenuddin, Syed ; Koehn, Madeline ; May, Ronald ; Chen, Horng H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-wolterskluwer_health_00003017-201811061-019563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><toplevel>online_resources</toplevel><creatorcontrib>Wan, Siu-Hin</creatorcontrib><creatorcontrib>Ameenuddin, Syed</creatorcontrib><creatorcontrib>Koehn, Madeline</creatorcontrib><creatorcontrib>May, Ronald</creatorcontrib><creatorcontrib>Chen, Horng H</creatorcontrib><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wan, Siu-Hin</au><au>Ameenuddin, Syed</au><au>Koehn, Madeline</au><au>May, Ronald</au><au>Chen, Horng H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Abstract 14444: Type 2 Diabetic Rat Model With Low Dose Streptozotocin and High Fat Diet: Characterizing Cardiorenal Function and Fibrosis in Diabetic Cardiomyopathy</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><date>2018-11-06</date><risdate>2018</risdate><volume>138</volume><issue>Suppl_1 Suppl 1</issue><spage>A14444</spage><epage>A14444</epage><pages>A14444-A14444</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><abstract><![CDATA[IntroductionHigh dose streptozotocin (STZ) injection results in pancreatic destruction and a type 1 diabetic (T1DM) rat model. Low dose STZ with high fat diet may represent a type 2 diabetes (T2DM) insulin-resistance model, which would allow for greater translational investigation into cardiorenal complications of T2DM.PurposeThe objective is to establish and characterize cardiorenal function and fibrosis in a type 2 diabetes rat model.MethodsTen week old male Wistar rats were divided into three groupscontrol n=23, type 1 DM n=17 and type 2 DM n=11. Rats in the type 1 DM group were injected STZ at 65 mg/kg intraperitoneally and fed regular diet. Rats in T2DM were injected with two doses of STZ at 35 mg/kg within 24 hours and fed high fat diet. Rats in the control group were injected with citrate buffer (pH 5.0) and fed regular diet. Weights, blood glucose, and 24-hour urine collection were recorded. After 3 months, rats were anesthetized, blood and urine collected, and tissues harvested for histological analysis.ResultsDiabetes was confirmed in the T1DM and T2DM vs control group (plasma glucose 443±19 and 350±11 vs 114±4 mg/dL). However, blood glucose was lower in T2DM vs T1DM (p<0.01). Plasma insulin was not statistically different between the control and T2DM groups (0.67±0.08 and 0.30±0.05 ng/mL, p=0.97) but lower in the T1DM group (0.04±0.01 ng/mL, p<0.01). By picrosirius staining, LV interstitial, kidney cortex, and pancreas fibrosis were greater in the T2DM vs control group (2.75±0.27 vs 1.08±0.12% p<0.01; 7.97±0.53 vs 1.95±0.23% p<0.01; 5.47±0.37 vs 1.87±0.29%, p<0.01, respectively). There was greater 24 hour urine protein excretion in T1DM and T2DM vs control group (1.73±0.16 and 9.94±2.55 vs 0.78±0.10 mg/min, p<0.01). Plasma cGMP was higher in the T1DM and T2DM vs control group (10.15±1.05 and 8.85±1.21 vs 4.27±0.49 pmol/min, p<0.01).ConclusionsT2DM was successfully induced in a low dose streptozotocin high fat diet rat model, as confirmed by increased plasma glucose but preserved plasma insulin levels. Significant increases in fibrosis, urine protein, and plasma cGMP in the T2DM vs control group represent a viable rat model for investigation of cardiorenal complications of T2DM with non-insulin anti-glycemic agents.]]></abstract><pub>by the American College of Cardiology Foundation and the American Heart Association, Inc</pub></addata></record>
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title Abstract 14444: Type 2 Diabetic Rat Model With Low Dose Streptozotocin and High Fat Diet: Characterizing Cardiorenal Function and Fibrosis in Diabetic Cardiomyopathy
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