title: Effect of impaired glucose tolerance on atherosclerotic lesion formation: an evaluation in selectively bred mice with different susceptibilities to glucose intolerance.
abstract: OBJECTIVE
  Impaired glucose tolerance (IGT) is an independent risk factor for atherosclerotic cardiovascular disease. However, due to the lack of appropriate animal models, the underlying mechanisms for IGT-induced atherosclerosis remain to be elucidated in vivo. We recently used selective breeding to establish 2 mouse lines with distinctively different susceptibilities to diet-induced glucose intolerance, designated selectively bred diet-induced glucose intolerance-resistant (SDG-R) and SDG-prone (SDG-P), respectively. Here, we assessed atherosclerotic lesion formation in these mice.
  
  
  METHODS
  Female SDG-R and SDG-P mice were fed an atherogenic diet (AD; 1.25% cholesterol, 0.5% sodium cholate, and 36% energy as fat) for 20 weeks (8-28 weeks of age). Oral glucose tolerance tests were performed during the AD-feeding period. Atherosclerotic lesion formation was quantitatively analyzed in serial aortic sinus sections by oil red O staining. Plasma lipids were measured after the AD-feeding period.
  
  
  RESULTS
  Glucose tolerance was impaired in SDG-P mice as compared to SDG-R mice over the 20-week AD-feeding period. No significant differences were observed in any plasma lipid measurement between the 2 mouse lines. Aortic sinus atherosclerotic lesion formation in SDG-P mice was approximately 4-fold greater than that in SDG-R mice.
  
  
  CONCLUSIONS
  In 2 mouse lines with different susceptibilities to diet-induced glucose intolerance, IGT accelerated atherosclerotic lesion formation. These mice may therefore serve as useful in vivo models for investigating the causal role of IGT in the pathogenesis of atherosclerosis.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Asai
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Nagao
authors.forename: Momoyo
authors.initials: M
authors.lastname: Kawahara
authors.forename: Yuki
authors.initials: Y
authors.lastname: Shuto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sugihara
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oikawa
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D001786:Blood Glucose; D001835:Body Weight; D002318:Cardiovascular Diseases / Q000235:genetics; D004032:Diet; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease; D018149:Glucose Intolerance / Q000097:blood*; D005951:Glucose Tolerance Test; D008055:Lipids / Q000097:blood; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012307:Risk Factors; D013045:Species Specificity; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D008055:Lipids
keywords: Animal model; Atherosclerosis; Impaired glucose tolerance; Postprandial hyperglycemia