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Original Article
Effects of Spironolactone and Losartan on Diabetic Nephropathy in a Type 2 Diabetic Rat Model
Mi Young Lee, Myoung Sook Shim, Bo Hwan Kim, Soon Won Hong, Ran Choi, Eun Young Lee, Soo Min Nam, Gun Woo Kim, Jang Yel Shin, Young Goo Shin, Choon Hee Chung
Diabetes Metab J. 2011;35(2):130-137.   Published online April 30, 2011
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  • 64 Download
  • 15 Crossref
AbstractAbstract PDFPubReader   

While there is an evidence that the anti-inflammatory properties of spironolactone can attenuate proteinuria in type 2 diabetes, its effects on vascular endothelial growth factor (VEGF) expression in diabetic nephropathy have not been clearly defined. In this study, we examined the effects of spironolactone, losartan, and a combination of these two drugs on albuminuria, renal VEGF expression, and inflammatory and oxidative stress markers in a type 2 diabetic rat model.


Thirty-three Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats were divided into four groups and treated with different medication regimens from weeks 25 to 50; OLETF diabetic controls (n=5), spironolactone-treated (n=10), losartan-treated (n=9), and combination of spironolactone- and losartan-treated (n=9).


At week 50, the albumin-to-creatinine ratio was significantly decreased in the losartan and combination groups compared to the control OLETF group. No decrease was detected in the spironolactone group. There was a significant reduction in renal VEGF, transforming growth factor (TGF)-β, and type IV collagen mRNA levels in the spironolactone- and combination regimen-treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were comparable in all four groups but did show a decreasing trend in the losartan and combination regimen groups. Twenty-four hour urine malondialdehyde levels were significantly decreased in the spironolactone- and combination regimen-treated groups.


These results suggest that losartan alone and a combined regimen of spironolactone and losartan could ameliorate albuninuria by reducing renal VEGF expression. Also, simultaneous treatment with spironolactone and losartan may have protective effects against diabetic nephropathy by decreasing TGF-β and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.


Citations to this article as recorded by  
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    Mahyar Khazaeli, Ane C. F. Nunes, Yitong Zhao, Mahziar Khazaali, John Prudente, Nosratola D. Vaziri, Bhupinder Singh, Wei Ling Lau
    Pharmacology Research & Perspectives.2023;[Epub]     CrossRef
  • Type 2 Diabetes Mellitus: Pathogenic Features and Experimental Models in Rodents
    Inessa G. Gvazava, M. V. Karimova, A. V. Vasiliev, E. A. Vorotelyak
    Acta Naturae.2022; 14(3): 57.     CrossRef
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    Drug Development Research.2021; 82(3): 341.     CrossRef
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    Biochemical Pharmacology.2021; 192: 114712.     CrossRef
  • Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease
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    Frontiers in Pharmacology.2021;[Epub]     CrossRef
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  • Bioactive Agent Discovery from the Natural Compounds for the Treatment of Type 2 Diabetes Rat Model
    Shih-Chun Yang, Ching-Yun Hsu, Wei-Ling Chou, Jia-You Fang, Shih-Yi Chuang
    Molecules.2020; 25(23): 5713.     CrossRef
  • Losartan improves renal function and pathology in obese ZSF-1 rats
    Zhi Su, Deborah Widomski, Arthur Nikkel, Laura Leys, Marian Namovic, Diana Donnelly-Roberts, Murali Gopalakrishnan, Steve McGaraughty
    Journal of Basic and Clinical Physiology and Pharmacology.2018; 29(3): 281.     CrossRef
  • Analyzing polymeric nanofibrous scaffold performances in diabetic animal models for translational chronic wound healing research
    Nowsheen Goonoo, Archana Bhaw-Luximon
    Nanotechnology Reviews.2017; 6(6): 583.     CrossRef
  • Stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in type 2 diabetes with nephropathy
    Motonobu Nakamura, Nobuhiko Satoh, Masashi Suzuki, Haruki Kume, Yukio Homma, George Seki, Shoko Horita
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  • Combination therapy with spironolactone and candesartan protects against streptozotocin-induced diabetic nephropathy in rats
    Amal Hofni, Mohamed A. El-Moselhy, Ashraf Taye, Mohamed M. Khalifa
    European Journal of Pharmacology.2014; 744: 173.     CrossRef
  • Renal Protective Role of Xiexin Decoction with Multiple Active Ingredients Involves Inhibition of Inflammation through Downregulation of the Nuclear Factor-κB Pathway in Diabetic Rats
    Jia-sheng Wu, Rong Shi, Jie Zhong, Xiong Lu, Bing-liang Ma, Tian-ming Wang, Bin Zan, Yue-ming Ma, Neng-neng Cheng, Fu-rong Qiu
    Evidence-Based Complementary and Alternative Medicine.2013; 2013: 1.     CrossRef
  • The use of animal models in diabetes research
    Aileen JF King
    British Journal of Pharmacology.2012; 166(3): 877.     CrossRef
  • Effect of Eplerenone, a Selective Aldosterone Blocker, on the Development of Diabetic Nephropathy in Type 2 Diabetic Rats
    Jae Hee Ahn, Ho Cheol Hong, Myong Jin Cho, Yoon Jung Kim, Hae Yoon Choi, Chai Ryoung Eun, Sae Jeong Yang, Hye Jin Yoo, Hee Young Kim, Ji A Seo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Nan Hee Kim
    Diabetes & Metabolism Journal.2012; 36(2): 128.     CrossRef
Case Reports
A Case of Concurrent Emphysematous Pyelonephritis and Emphysematous Cholecystitis in a Patient with Diabetes Mellitus.
Se Hyung Lee, Ji Hoon Kim, Jong Young Lee, Tae Hyuck Choi, Gil Hyun Gang, Myoung Sook Shim, Jin Yub Kim
Korean Diabetes J. 2005;29(3):262-266.   Published online May 1, 2005
  • 1,221 View
  • 17 Download
AbstractAbstract PDF
Several unusual infections such as malignant otitis externa, rhinocerebral mucormycosis, emphysematous pyelonephritis and emphysematous cholecystitis exclusively occur in diabetic patients. Each of these diseases is a rare, but potentially life-threatening infection. Therefore, prompt diagnosis and early medical and operative intervention will be necessary for these diseases. We report herein a very rare case in which emphysematous pyelonephritis and emphysematous cholecystitis were simultaneously diagnosed. A 45-year-old man, who was previously diagnosed with secondary diabetes mellitus due to chronic alcoholic pancreatitis ten years earlier, presented with fever and right upper quadrant abdominal pain for 3 days. Abdominal computed tomography showed an air-fluid level in the lumen of the gall bladder and there was gas collection within the right renal parenchyma. Broad-spectrum antibiotics therapy was initiated and cholecystectomy and right nephrectomy were performed. Escherichia coli bacteria were isolated from the culture of the blood, urine and sputum. The patient recovered and was discharged in a healthy state
Hemichorea Associated with Type II Diabetes Mellitus.
Ju Hee Maeng, Hee Sup Lee, Jin Gun Jang, Bae Gun Park, Kwang Deog Jo, Myoung Sook Shim, Jin Yub Kim
Korean Diabetes J. 2003;27(4):362-366.   Published online August 1, 2003
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  • 16 Download
AbstractAbstract PDF
Hemichorea has been reported as a rare complication of nonketotic hyperglycemia. We report a diabetic patient who developed paroxysmal hemichorea. When hyperglycemia is corrected, the movement disorder resolves within a few days. The MR images showed high signal intensity on T1-weighted images and low signal intensity on T2-weighted images in the left basal ganglia contralateral to the involuntary movement. We present a case of hemichorea in a poorly controlled diabetic patient.
Original Article
The Effect of Chronic Alcohol Intake on Insulin Secretion in NIDDM Rats.
Mi Jin Kim, Myoung Sook Shim, Mun Kyu Kim, Dong Gu Kang, Hyung Suk Park, Sang Man Chung, Tae Sun Hwang, Young Goo Shin, Choon Jo Chin, Choon Hee Chung
Korean Diabetes J. 2002;26(5):366-376.   Published online October 1, 2002
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  • 19 Download
AbstractAbstract PDF
The effect of alcohol on glucose metabolism is dependent on the daily amount of alcohol ingestion and the timing of intake. Heavy alcohol consumption in the fasting state may lead to serious hypoglycemia, whereas an excessive alcohol intake during meals may lead to hyperglycemia. In Korea, AIDDM (atypical insulin dependent diabetes mellitus) which shows firstly similar to the NIDDM and progresses slowly into IDDM is related to heavy alcohol drinking. So we studied that the effect of chronic alcohol intake on insulin secretion of beta cell in streptozotocin (STZ)-induced non-insulin dependent diabetic Sprangue- Dawley rats. METHODS: 40 male newborn (12 hours old) Sprague-Dawley rats were made diabetic by streptozotocin (50 mg/kg, intraperitoneal injection) and 20 male newborn (12 hours old) Sprague-Dawley rats were injected by citrate buffer solution. At 14 weeks old, diabetic group were confirmed by intraperitoneal glucose tolerance test (30% D/W, 2 g/kg). After that, diabetic group were divided into two groups. One group were fed on 5% ethanol and the other group were fed on water for 8 weeks. Control groups were divided into two groups. One group were fed on 5% ethanol and the other group were fed on water for 8 weeks. All rats were divided into 4 groups; group I: diabetic and 5% ethanol, group II: non- diabetic and 5% ethanol, group III: diabetic and water, group IV: non-diabetic and water. At the age of 22 weeks, we determined insulin level among 4 groups. After we extracted pancreas, determined the ratio of area of beta cell to islet cell. RESULTS: 1) There was no difference of weight among 4 groups in 22 week old rats. 2) Group I freely ingested 2.08g (5.50 g/kg/day) ethanol daily and group II ingested 2.04g (4.89g/kg/day) ethanol daily. 3) Plasma insulin levels of group I were lower than those of group III but not significant. 4) Plasma insulin levels of group II were higher than those of group IV but not significant. 5) In the light microscopic findings of pancreas, the ratios of area of beta cells to islet cells in group I were the lowest but not significant. CONCLUSION: These findings suggested that chronic moderate alcohol ingestion in NIDDM rats didn't impair insulin secretion and morphology of pancreatic beta cells.

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