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- W2289774804 abstract "Patients with obesity develop peripheral insulin resistance, hyperinsulinemia, and hypertension that are associated with cardiovascular disease and death. Hyperinsulinemia increases renal sodium reabsorption, in part through the epithelial sodium channel (ENaC) of the distal nephron, and may increase blood pressure. The molecular determinants of this process are poorly understood, and a mouse model is needed to facilitate discovery. We systematically characterized five potential diet-induced models of the metabolic syndrome in C57BL/6J mice. We measured sodium avidity, ENaC-mediated sodium reabsorption in whole animal and in ex vivo microperfusion experiments as well as blood pressure by radiotelemetry. High-fat (45% or 60% kcal) diet-fed (HFD) mice developed obesity and hyperinsulinemia after 6 weeks while fructose-fed mice lacked hyperinsulinemia. HFD mice demonstrated increased sodium avidity compared to low-fat (10% kcal) fed (LFD) mice as measured by urine sodium excretion after transition to a high salt diet. Interestingly, HFD animals did not have increased ENaC activity as measured by metabolic cage studies utilizing the ENaC antagonist, benzamil, or microperfusion of the cortical collecting duct. Blood pressure was significantly different in HFD vs. LFD mice, when active and while awake, but not at rest. HFD mice display manifestations of the metabolic syndrome including increased sodium avidity, which was not mediated through ENaC as has been previously described. In contrast to insulin infusion studies, HFD mice developed increased blood pressure that was both statistically and clinically significant during selected intervals in a 24-hour cycle. Grant Funding Source: Supported by Child Health Research Institute, Stanford CTSA, and National Institutes of Health" @default.
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- W2289774804 date "2014-04-01" @default.
- W2289774804 modified "2023-09-27" @default.
- W2289774804 title "ENaC‐independent impaired natriuresis and increased blood pressure in mouse models of diet‐induced hyperinsulinemia (1086.3)" @default.
- W2289774804 doi "https://doi.org/10.1096/fasebj.28.1_supplement.1086.3" @default.
- W2289774804 hasPublicationYear "2014" @default.
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