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Title: Direct renin inhibition modulates insulin resistance in caveolin-1-deficient mice
Authors: Chuengsamarn S.
Garza A.E.
Krug A.W.
Romero J.R.
Adler G.K.
Williams G.H.
Pojoga L.H.
Keywords: aliskiren
caveolin 1
animal cell
animal experiment
animal model
animal tissue
blood pressure regulation
controlled study
glucose blood level
glucose tolerance test
insulin blood level
insulin resistance
metabolic syndrome X
priority journal
treatment duration
treatment response
triacylglycerol blood level
wild type
Antihypertensive Agents
Blood Glucose
Blood Pressure
Caveolin 1
Disease Models, Animal
Glucose Tolerance Test
Insulin Resistance
Metabolic Syndrome X
Mice, Knockout
Random Allocation
Issue Date: 2013
Abstract: Objective: To test the hypothesis that aliskiren improves the metabolic phenotype in a genetic mouse model of the metabolic syndrome (the caveolin-1 (cav-1) knock out (KO) mouse). Materials/Methods: Eleven-week-old cav-1 KO and genetically matched wild-type (WT) mice were randomized to three treatment groups: placebo (n = 8/group), amlodipine (6 mg/kg/day, n = 18/ group), and aliskiren (50 mg/kg/day, n = 18/ group). After three weeks of treatment, all treatment groups were assessed for several measures of insulin resistance (fasting insulin and glucose, HOMA-IR, and the response to an intraperitoneal glucose tolerance test (ipGTT)) as well as for triglyceride levels and the blood pressure response to treatment. Results: Treatment with aliskiren did not affect the ipGTT response but significantly lowered the HOMA-IR and insulin levels in cav-1 KO mice. However, treatment with amlodipine significantly degraded the ipGTT response, as well as the HOMA-IR and insulin levels in the cav-1 KO mice. Aliskiren also significantly lowered triglyceride levels in the cav-1 KO but not in the WT mice. Moreover, aliskiren treatment had a significantly greater effect on blood pressure readings in the cav-1 KO vs. WT mice, and was marginally more effective than amlodipine. Conclusions: Our results support the hypothesis that aliskiren reduces insulin resistance as indicated by improved HOMA-IR in cav-1 KO mice whereas amlodipine treatment resulted in changes consistent with increased insulin resistance. In addition, aliskiren was substantially more effective in lowering blood pressure in the cav-1 KO mouse model than in WT mice and marginally more effective than amlodipine. © 2013 Elsevier Inc.
ISSN: 260495
Appears in Collections:SCOPUS 1983-2021

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