| Beneficial effect of insulin in hyperhomocysteinemia and diabetes mellitus-induced vascular endothelium dysfunction: role of phosphoinositide dependent kinase and protein kinase B. | |
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MedLine Citation:
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PMID: 21069435 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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A primary defect in the vascular action of insulin may be the key intermediate mechanism that links endothelial dysfunction with diabetes mellitus and hyperhomocysteinemia. This study investigated the downstream targets of insulin, involved in this process. Hyperhomocysteinemia (serum homocysteine > 10 μm/l) was produced in rats by administering L-methionine (1.7% w/w, p.o.x. 4 weeks) and diabetes mellitus (serum glucose > 140 mg/dl) was induced using streptozotocin (55 mg/kg/day, i.v. once) in another group. Four weeks after L-methionine and streptozotocin administration, vascular endothelium dysfunction was assessed in terms of attenuation of acetylcholine-induced, endothelium-dependent relaxation (isolated aortic ring preparation), decrease in serum nitrate/nitrite level, as well as mRNA expression of eNOS (rtPCR), and disruption of integrity of vascular endothelium. Both hyperhomocysteinemia and diabetes mellitus significantly attenuated acetylcholine-induced endothelial-dependent relaxation, and the increase in serum nitrite/nitrate concentration and the expression of eNOS. Insulin (0.4 and 0.6 IU/kg/day, s.c.) and atorvastatin (30 mg/kg/day, p.o.x. 4 weeks) significantly improved all these parameters. However, this ameliorative effect of insulin was blocked by 7-hydroxystaurosporine (UCN-01) [Inhibitor of phosphoinositide dependent kinase (PDK)], and triciribine (API-2) (protein kinase B/Akt inhibitor). It is suggested that amelioration of vascular endothelium dysfunction by insulin may be due to stimulation of PDK and Akt pathways. |
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Authors:
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Saurabh Sharma; Manjeet Singh; Pyare Lal Sharma |
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Publication Detail:
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Type: Journal Article Date: 2010-11-11 |
Journal Detail:
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Title: Molecular and cellular biochemistry Volume: 348 ISSN: 1573-4919 ISO Abbreviation: Mol. Cell. Biochem. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-06 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0364456 Medline TA: Mol Cell Biochem Country: Netherlands |
Other Details:
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Languages: eng Pagination: 21-32 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India. suns.saurabh@gmail.com |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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