Document Detail

Characterizing the mechanisms of insulin vasodilatation of normal and streptozotocin-induced diabetic rat aorta.
MedLine Citation:
PMID:  19295443     Owner:  NLM     Status:  MEDLINE    
The mechanism by which insulin causes vasodilatation remains unclear, so we explored this in aortic rings from normal Wistar Kyoto and streptozotocin-induced diabetic rats. Insulin-induced relaxation of phenylephrine-contracted [endothelium (ED) intact or denuded] aortic rings was recorded in the presence or absence of various drug probes. Insulin relaxant effect was more in ED-intact than in-denuded tissues from normal or diabetic rats. l-NAME or methylene blue partially inhibited insulin effect in ED-intact but not the ED-denuded tissues, whereas indomethacin (cyclooxygenase inhibitor) had no effect on any of the tissues, indicating that insulin induces relaxation by ED-dependent and -independent mechanisms, the former via the NOS-cyclic guanosine monophosphate but not the cyclooxygenase pathway. The voltage-dependent K channel (KV) blocker (4-aminopyridine) inhibited insulin action in all the tissues (normal or diabetic, with or without ED), whereas the selective BKCa blocker, tetraethylammonium, inhibited it in normal (ED intact or denuded) but not in diabetic tissues, indicating that KV mediates insulin action in normal and diabetic tissues, whereas the BKCa mediates it only in normal tissues, with possible pathophysiologic absence in diabetic tissues. The inward rectifier K channel (Kir) blocker (barium chloride) significantly inhibited insulin effect only in ED-intact or -denuded diabetic tissues, whereas the KATP channel blocker, glibenclamide, inhibited it only in the ED-denuded diabetic tissues, suggesting that Kir channels mediate insulin-induced relaxation in ED-intact or -denuded diabetic tissues, whereas the KATP channel mediates it in ED-denuded diabetic tissues. All the agents combined did not abolish insulin action, suggestive of a direct vasodilatory effect. In conclusion, insulin causes vasodilatation in normal and diabetic tissues via ED-dependent and -independent mechanisms differentially modulated by K channels, some of which functions are altered in diabetes and thus are potential therapeutic targets.
G Subramaniam; Francis I Achike; M R Mustafa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  53     ISSN:  1533-4023     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-27     Completed Date:  2009-07-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  333-40     Citation Subset:  IM    
Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
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MeSH Terms
Aorta, Thoracic / drug effects*
Diabetes Mellitus, Experimental / metabolism*
Dose-Response Relationship, Drug
Insulin / pharmacology*
Rats, Inbred WKY
Streptozocin / pharmacology
Vasodilation / drug effects*,  physiology
Vasodilator Agents / pharmacology*
Reg. No./Substance:
0/Vasodilator Agents; 11061-68-0/Insulin; 18883-66-4/Streptozocin

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