title: Hyperinsulinemia does not change atherosclerosis development in apolipoprotein E null mice.
abstract: OBJECTIVE
  To determine the contribution of hyperinsulinemia to atherosclerosis development.
  
  
  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.affiliation: Research Division, Joslin Diabetes Center, Boston, MA, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Rask-Madsen
authors.forename: Erica
authors.initials: E
authors.lastname: Buonomo
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Kyoungmin
authors.initials: K
authors.lastname: Park
authors.forename: Allen C
authors.initials: AC
authors.lastname: Clermont
authors.forename: Oluwatobi
authors.initials: O
authors.lastname: Yerokun
authors.forename: Mark
authors.initials: M
authors.lastname: Rekhter
authors.forename: George L
authors.initials: GL
authors.lastname: King
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006946:Hyperinsulinism / Q000097:blood / Q000150:complications* / Q000235:genetics; D055504:Insulin Receptor Substrate Proteins / Q000096:biosynthesis / Q000235:genetics; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction
chemical_list: D001057:Apolipoproteins E; D055504:Insulin Receptor Substrate Proteins