| Direct renin inhibition improved insulin resistance and adipose tissue dysfunction in type 2 diabetic KK-A(y) mice. | |
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MedLine Citation:
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PMID: 20543712 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: The renin-angiotensin system affects insulin sensitivity mainly through the angiotensin II type 1 receptor. In this study, the effects of renin inhibition on insulin resistance and adipose tissue dysfunction were explored in type 2 diabetic KK-A(y) mice. METHODS AND RESULTS: Male KK-A mice were treated with a direct renin inhibitor, aliskiren, administered subcutaneously at a dose of 50 mg/kg per day for 14 days using an osmotic minipump. This dose of aliskiren strongly inhibited plasma renin activity and lowered blood pressure about 17% in KK-A(y) mice. Aliskiren decreased body weight and plasma glucose level, and increased plasma insulin level in a fed condition. Aliskiren also lowered the plasma levels of cholesterol, fatty acids and triglycerides. In the oral glucose tolerant test, the plasma glucose elevation after glucose load was reduced by aliskiren, without a significant change in insulin level. Insulin tolerance test showed that aliskiren enhanced insulin's effect on plasma glucose. Aliskiren also reduced the epididymal adipose tissue mass by 25% and retroperitoneal adipose tissue mass by 35%. In adipose tissue, expression of the insulin receptor was not changed by aliskiren; however, expression of insulin receptor substrate-1, glucose transporter type 4, adiponectin, peroxisome proliferator-activated receptor-gamma and CCAAT/enhancer-binding proteindelta was increased by aliskiren. Moreover, NADPH oxidase activity and expression of inflammatory factors were reduced in adipose tissue. Aliskiren increased the pancreatic beta-cell area in KK-A(y) mice. CONCLUSION: These results suggest that renin inhibition by aliskiren improved insulin resistance and adipose tissue dysfunction in type 2 diabetic mice through an increase in insulin sensitivity, insulin secretion and adipocyte differentiation, and a reduction of oxidative stress. |
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Authors:
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Masaru Iwai; Harumi Kanno; Yumiko Tomono; Shinji Inaba; Izumi Senba; Megumi Furuno; Masaki Mogi; Masatsugu Horiuchi |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of hypertension Volume: 28 ISSN: 1473-5598 ISO Abbreviation: J. Hypertens. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-24 Completed Date: 2010-12-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: England |
Other Details:
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Languages: eng Pagination: 1471-81 Citation Subset: IM |
Affiliation:
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Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adiponectin
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metabolism,
pharmacology,
therapeutic use Adipose Tissue / drug effects*, metabolism, physiopathology Amides / pharmacology* Animals Chymosin / metabolism, pharmacology, therapeutic use Diabetes Mellitus, Experimental / physiopathology Diabetes Mellitus, Type 2 / drug therapy, metabolism* Fumarates / pharmacology* Glucose / metabolism, pharmacology, therapeutic use Glucose Transporter Type 4 / metabolism Insulin / blood, metabolism, pharmacology Insulin Receptor Substrate Proteins / metabolism Insulin Resistance / physiology* Male Mice PPAR gamma / metabolism, pharmacology, therapeutic use Renin / antagonists & inhibitors*, metabolism, pharmacology Renin-Angiotensin System / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Adiponectin; 0/Amides; 0/Fumarates; 0/Glucose Transporter Type 4; 0/Insulin Receptor Substrate Proteins; 0/PPAR gamma; 0/aliskiren; 11061-68-0/Insulin; 50-99-7/Glucose; EC 3.4.23.15/Renin; EC 3.4.23.4/Chymosin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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