Interactions of PPAR α and GLUT4 in DOCA/salt-induced renal injury in mice

[摘要] Diminished insulin sensitivity is a characteristic feature of various pathological conditions such as hypertension and activation of peroxisome proliferator activated receptor α (PPARα) has been shown to enhance insulin resistance and reduce capacity for glucose uptake in muscles. The present study was designed to evaluate the interactions of PPARα and GLUT4 in a model of hypertensive renal injury by studying deoxycorticosterone acetate (DOCA)-salt induced hypertension in wild-type (WT) and PPARα knockout (KO) mice. PPARα WT and KO mice were uninephrectomized (UNx) and implanted subcutaneously DOCA and drank 1% sodium chloride/1% potassium chloride with or without a GLUT4 antagonist, indinavir (20 mg/kg/day, s.c) or PPARα ligand, fenofibrate (100 mg/kg/day, orally). DOCA/salt treatment increased urinary sodium excretion and urine volume (p<0.05) in PPARα KO mice compared to WT littermates. Indinavir increased proteinuria (p<0.01) in DOCA/salt-treated PPARα KO mice compared to WT littermates but did not affect heart and kidney weight index in DOCA/salt KO or WT-treated mice. Urinary sodium excretion (U

[学科分类] 内科医学

[关键词] DOCA;Indinavir;Fenofibrate;PPARα;Nephropathy;GLUT4