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|Title:||Role of glucagon-like peptide-1 in vascular endothelial dysfunction|
Bijjem, Krishnareddy V
|Keywords:||Diabetes mellitus;Exendin-4;Hyperhomocysteinemia;Vascular endothelial dysfunction|
|Abstract:||The present study has been undertaken to investigate the effect of exendin-4 (a glucagon-like peptide-1 agonist) in diabetes mellitus (DM) and hyperhomocysteinemia (HHcy)-induced vascular endothelial dysfunction (VED). Streptozotocin (55 mg kg−1, iv, once) and methionine (1.7% w/w, po, 4 weeks) were administered to rats to produce DM (serum glucose >200 mg dl−1) and HHcy (serum homocysteine >10 μM) respectively. VED was assessed using isolated aortic ring preparation, microscopy of thoracic aorta, and serum nitrite/nitrate concentration. Serum TBARS concentration was estimated to assess oxidative stress. Atorvastatin has been employed as standard agent. Exendin-4 (1 μg kg−1, ip) and atorvastatin (30 mg kg−1, po) treatments significantly attenuated increase in serum glucose and homocysteine but their concentrations remained markedly higher than sham control value. Exendin-4 and atorvastatin treatments markedly prevented DM and HHcy-induced (i) attenuation of acetylcholine-induced endothelium-dependent relaxation, (ii) impairment of vascular endothelial lining, (iii) decrease in serum nitrite/nitrate concentration, and (iv) increase in serum TBARS. However, this ameliorative effect of exendin-4 has been prevented by L-NAME (25 mg kg-1, ip), an inhibitor of NOS. It may be concluded that exendin-4 may activate eNOS due to activation of GLP-1 and consequently reduce oxidative stress to improve vascular endothelial dysfunction.|
|ISSN:||0975-1009 (Online); 0019-5189 (Print)|
|Appears in Collections:||IJEB Vol.48(01) [January 2010]|
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