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Angiotensin receptor blockade and glucagon like peptide‐1 receptor activation ameliorates NADPH oxidase 4‐associated oxidative injury in insulin‐resistant rats
Author(s) -
Escobedo Benny,
Rodriguez Ruben,
Nishiyama Akira,
Moreno Meagan,
Ortiz Rudy
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1218.6
Subject(s) - medicine , endocrinology , nadph oxidase , oxidative stress , diabetic nephropathy , exenatide , chemistry , angiotensin ii , kidney , receptor , diabetes mellitus , type 2 diabetes
Diabetic nephropathy is associated with oxidative stress and increased renal NADPH oxidase 4 protein expression. Glucagon‐like peptide‐1 receptor (GLP‐1r) activation decreases glomerular NOX 4 expression and albumin excretion in streptozotocin‐induced diabetic rats. Angiotensin receptor type 1 (AT 1 ) blockade improves renal oxidative injury via downregulation of NOX 4 and reducing urinary albumin excretion. To test the hypothesis that the combination of GLP‐1r activation and AT 1 blockade decreases oxidative stress and subsequent kidney damage, we measured renal NOX 4 protein expression and albumin excretion in five rat groups: 1) untreated, lean LETO (n=7), 2) untreated, obese OLETF (n=9), 3) OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan /kg/d; n=9), 4) OLETF + GLP‐1 mimetic (Exe; 10 ug exenatide/kg/d; n=7), and 5) OLETF + ARB + exenatide (combo; n=6). Albumin excretion increased in OLETF compared to LETO; whereas, ARB and Exe decreased it, and combo treatment decreased it further. Renal NOX 4 protein expression increased 23% in OLETF compared to LETO. Exe and ARB decreased NOX 4 protein expression in OLETF rats by 18% and 14% respectively, while the combo treatment decreased it further by 24%. These data suggest that AT 1 blockade and GLP‐1r activation ameliorate oxidative renal injury, highlighting the impact of the activation of these receptors in the pathogenesis of diabetes‐associated renal impairments.