Oral insulin supplementation attenuates atherosclerosis progression in apolipoprotein E-deficient mice

Raanan Shamir*, Naim Shehadeh, Mira Rosenblat, Orly Eshach-Adiv, Raymond Coleman, Marielle Kaplan, Shadi Hamoud, Sophie Lischinsky, Tony Hayek

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Objective - The role of insulin in atherosclerosis progression in diabetes is uncertain. We examined the effects of oral insulin supplementation on atherogenesis in apolipoprotein E-deficient (E0) mice. Methods and Results - One-month-old male E0 mice were orally supplemented with human insulin (0.1, 0.5, and 1 U/mL) or placebo for 3 months. At the end of the study, serum and macrophage oxidative stress and atherosclerosis progression were studied. Insulin reduced lesion size by 22% to 37% (P<0.05) in all study groups. Lipid peroxides serum levels were 18% lower (P<0.01), and serum paraoxonase activity was 30% higher (P<0.01) in mice supplemented with 1.0 U/mL insulin compared with controls. Insulin reduced mouse peritoneal macrophage (MPM) lipid peroxides content and superoxide anion release by up to 44% and 62%, respectively (P<0.01). In addition, oral insulin reduced MPM cholesterol content and cholesterol biosynthesis by up to 36% and 53%, respectively (P<0.01). In vitro incubation of E0 mice MPM with increasing insulin concentrations (0 to 100 μU/mL) resulted in a dose-dependent reduction of cholesterol synthesis by up to 66% (P<0.05). Conclusions - In E0 mice, oral insulin supplementation attenuates the atherosclerotic process. This may be attributable to insulin-mediated reduction of oxidative stress in serum and macrophages as well as reduction in macrophage cholesterol content.

Original languageEnglish
Pages (from-to)104-110
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number1
StatePublished - 1 Jan 2003
Externally publishedYes


  • Atherosclerosis
  • Macrophages
  • Oral insulin
  • Oxidative stress
  • Paraoxonase


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