Aliskiren improves insulin resistance and ameliorates diabetic renal vascular complications in STZ-induced diabetic rats.
Aliskiren, a direct renin inhibitor (DRI), has therapeutic effects in patients with hypertension and associated complications, but its potential mechanism in diabetic nephropathy is lacking. The effects of aliskiren in Streptozotocin (STZ)-induced renal complication in diabetic rats were investigated. Aliskiren treatment for eight weeks at the dose of 10 mg/kg/day, via osmotic mini-pump, induced improvement in blood glucose levels, systolic blood pressure (BP) and serum creatinine. Improvement of insulin resistance by aliskiren was confirmed by increased glucose translocation in liver and muscle and hence insulin levels. The treated group also showed improvement in glomerulosclerosis and tubulointerstitial injury. Aliskiren treatment also improved albumin levels in plasma, suppressed profibrotic and proinflammatory cytokine synthesis viz TNF-α and TGF-β and angiogenesis by a decrease in VEGF. In addition, the level of total proteins and GFR via cystatin c and beta-2microglobulin along with adiponectin and erythropoietin were also improved. These results suggest that the beneficial organ protective effect of aliskiren is mediated by improvement in insulin resistance as well as a direct anti-fibrotic effect in the target organ in STZ-induced diabetic rats with a slight effect on blood pressure. Aliskiren may be a useful therapeutic agent in the treatment of type 2 diabetes and diabetic nephropathy.
Delhi Institute of Pharmaceutical Sciences and Research, India. sonia.gandhi@rediffmail.com
Sonia
S
Gandhi
Bp
B
Srinivasan
Atul Sureshrao
AS
Akarte
D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005650:Fumarates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D012372:ROC Curve; D051381:Rats; D017208:Rats, Wistar
D000577:Amides; D015415:Biomarkers; D001786:Blood Glucose; D005650:Fumarates; D051273:Glucose Transporter Type 2; D051275:Glucose Transporter Type 4; D007328:Insulin; C495683:Slc2a2 protein, rat; C495694:Slc2a4 protein, rat; C446481:aliskiren