Document Detail


Hyperinsulinemia does not change atherosclerosis development in apolipoprotein E null mice.
MedLine Citation:
PMID:  22426129     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: To determine the contribution of hyperinsulinemia to atherosclerosis development.
METHODS AND RESULTS: Apolipoprotein E (Apoe) null mice that had knockout of a single allele of the insulin receptor (Insr) gene were compared with littermate Apoe null mice with intact insulin receptors. Plasma insulin levels in Insr haploinsufficient/Apoe null mice were 50% higher in the fasting state and up to 69% higher during a glucose tolerance test, but glucose tolerance was not different in the 2 groups. C-peptide levels, insulin sensitivity, and postreceptor insulin signaling in muscle, liver, fat, and aorta were not different between groups, whereas disappearance in plasma of an injected insulin analog was delayed in Insr haploinsufficient/Apoe null mice, indicating that impaired insulin clearance was the primary cause of hyperinsulinemia. No differences were observed in plasma lipids or blood pressure. Despite the hyperinsulinemia, atherosclerotic lesion size was not different between the 2 groups at time points up to 52 weeks of age when measured as en face lesion area in the aorta, cross-sectional plaque area in the aortic sinus, and cholesterol abundance in the brachiocephalic artery.
CONCLUSIONS: Hyperinsulinemia, without substantial vascular or whole-body insulin resistance and without changes in plasma lipids or blood pressure, does not change susceptibility to atherosclerosis.
Authors:
Christian Rask-Madsen; Erica Buonomo; Qian Li; Kyoungmin Park; Allen C Clermont; Oluwatobi Yerokun; Mark Rekhter; George L King
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-03-15
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  32     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-20     Completed Date:  2012-07-10     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1124-31     Citation Subset:  IM    
Affiliation:
Research Division, Joslin Diabetes Center, Boston, MA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apolipoproteins E / blood,  genetics*
Atherosclerosis / blood,  etiology,  genetics*
Disease Progression
Female
Gene Expression Regulation
Hyperinsulinism / blood,  complications*,  genetics
Insulin Receptor Substrate Proteins / biosynthesis,  genetics
Insulin Resistance*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Signal Transduction
Grant Support
ID/Acronym/Agency:
K08 EY018677/EY/NEI NIH HHS; K08EY018677/EY/NEI NIH HHS; P30DK036836/DK/NIDDK NIH HHS; R01 DK053105/DK/NIDDK NIH HHS; R01DK053105/DK/NIDDK NIH HHS; U24DK059637/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoproteins E; 0/Insulin Receptor Substrate Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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