title: Interactions of PPAR α and GLUT4 in DOCA/salt-induced renal injury in mice.
abstract: 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&lt;0.05) in PPARα KO mice compared to WT littermates. Indinavir increased proteinuria (p&lt;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 (UNaV) and urine volume (UV) were increased by indinavir (p&lt;0.01) and fenofibrate (p&lt;0.05) in DOCA/salt-treated PPARα KO mice compared to WT mice. Urinary nitric oxide was greater in both fenofibrate (p&lt;0.05) and indinavir-treated WT mice (p&lt;0.05) compared to KO mice. These data suggest that in hypertensive nephropathy, GLUT4 probably exerts a renoprotective role that was enhanced with the activation of PPARα receptors by a mechanism that may be related to increased nitric oxide production.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin. igbe.ighodaro@uniben.edu.
authors.forename: Igbe
authors.initials: I
authors.lastname: Ighodaro
authors.forename: Omogbai Kelly
authors.initials: OK
authors.lastname: Eric
authors.forename: Oyekan
authors.initials: O
authors.lastname: Adebayo
mesh_terms: D000818:Animals; D064791:Desoxycorticosterone Acetate; D004195:Disease Models, Animal; D011345:Fenofibrate / Q000494:pharmacology; D051275:Glucose Transporter Type 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019469:Indinavir / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018345:Mice, Knockout; D009392:Nephrectomy; D009569:Nitric Oxide / Q000652:urine; D047493:PPAR alpha / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011189:Potassium Chloride; D012964:Sodium / Q000652:urine; D012965:Sodium Chloride; D013997:Time Factors; D014554:Urination / Q000187:drug effects
chemical_list: D051275:Glucose Transporter Type 4; D047493:PPAR alpha; C495693:Slc2a4 protein, mouse; D009569:Nitric Oxide; D012965:Sodium Chloride; D019469:Indinavir; D011189:Potassium Chloride; D064791:Desoxycorticosterone Acetate; D012964:Sodium; D011345:Fenofibrate