| Insulin-induced generation of reactive oxygen species and uncoupling of nitric oxide synthase underlie the cerebrovascular insulin resistance in obese rats. | |
| | |
MedLine Citation:
|
PMID: 22234336 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Hyperinsulinemia accompanying insulin resistance (IR) is an independent risk factor for stroke. The objective is to examine the cerebrovascular actions of insulin in Zucker obese (ZO) rats with IR and Zucker lean (ZL) control rats. Diameter measurements of cerebral arteries showed diminished insulin-induced vasodilation in ZO compared with ZL. Endothelial denudation revealed vasoconstriction to insulin that was greater in ZO compared with ZL. Nonspecific inhibition of nitric oxide synthase (NOS) paradoxically improved vasodilation in ZO. Scavenging of reactive oxygen species (ROS), supplementation of tetrahydrobiopterin (BH(4)) precursor, and inhibition of neuronal NOS or NADPH oxidase or cyclooxygenase (COX) improved insulin-induced vasodilation in ZO. Immunoblot experiments revealed that insulin-induced phosphorylation of Akt, endothelial NOS, and expression of GTP cyclohydrolase-I (GTP-CH) were diminished, but phosphorylation of PKC and ERK was enhanced in ZO arteries. Fluorescence studies showed increased ROS in ZO arteries in response to insulin that was sensitive to NOS inhibition and BH(4) supplementation. Thus, a vicious cycle of abnormal insulin-induced ROS generation instigating NOS uncoupling leading to further ROS production underlies the cerebrovascular IR in ZO rats. In addition, decreased bioavailability and impaired synthesis of BH(4) by GTP-CH induced by insulin promoted NOS uncoupling.Journal of Cerebral Blood Flow & Metabolism advance online publication, 11 January 2012; doi:10.1038/jcbfm.2011.181. |
| | |
Authors:
|
Prasad V G Katakam; James A Snipes; Mesia M Steed; David W Busija |
Related Documents
:
|
17684446 - Genetic forms of the cardiometabolic syndrome: what can they tell the clinician? 8633616 - Genetic and environmental influences on insulin levels and the insulin resistance syndr... 16546286 - Haplotype combination of calpain-10 gene polymorphism is associated with metabolic synd... 11869176 - Alcohol consumption, the metabolic syndrome and insulin resistance in 58-year-old clini... 16389166 - Thrombin-activatable fibrinolysis inhibitor activity and global fibrinolytic capacity i... 7736346 - Effects of vanadium treatment on the alterations of cardiac glycogen phosphorylase and ... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-1-11 |
Journal Detail:
|
Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Volume: - ISSN: 1559-7016 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2012-1-11 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8112566 Medline TA: J Cereb Blood Flow Metab Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
1] Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana, USA [2] Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The two pathophysiologies of focal brain ischemia: implications for translational stroke research.
Next Document: In vivo mesolimbic D2/3 receptor binding predicts posttherapeutic clinical responses in restless leg...