title: Repetitive Glucose Spikes Accelerate Atherosclerotic Lesion Formation in C57BL/6 Mice.
abstract: BACKGROUND
  A number of epidemiological studies demonstrated that postprandial hyperglycemia is a risk factor for cardiovascular disease in individuals with impaired glucose tolerance. Although several laboratory studies have addressed the plausible causal role of postprandial acute hyperglycemia (glucose spikes) in the development of atherosclerosis, there is little convincing evidence in vivo whether the atherosclerotic lesion formation can be accelerated solely by glucose spikes. Here, we assessed the effect of repetitive glucose spikes on atherosclerotic lesion formation in mice.
  
  
  METHODS
  Female C57BL/6 mice were fed an atherogenic diet from 8 to 28 weeks of age. During the atherogenic diet feeding period, the mice orally received a glucose solution (50 mg glucose/mouse; G group) or water (W group) twice daily, 6 days a week. Atherosclerotic lesion formation in the aortic sinus was quantitatively analyzed in serial cross-sections by oil red O staining.
  
  
  RESULTS
  G group mice showed transient increases in blood glucose level (~5 mmol/L above W group), and the levels returned to levels similar to those in W group mice within 60 min. No significant differences in glucose tolerance, insulin sensitivity, and plasma lipid profiles were observed after the 20-week repetitive administration between the 2 groups. G group mice showed an approximately 4-fold greater atherosclerotic lesion size in the aortic sinus than W group mice. Gene expression levels of Cd68 and Icam1 in the thoracic aorta were higher in G group mice than in W group mice.
  
  
  CONCLUSIONS
  These results indicate that glucose spikes can accelerate atherosclerotic lesion formation, with little influence on other metabolic disorders. Repetitive glucose administration in wild-type mice may serve as a simple and useful approach to better understanding the causal role of glycemic spikes in the development of atherosclerosis.
authors: Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors: Yuki
authors: Y
authors: Shuto
authors: Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors: Akira
authors: A
authors: Asai
authors: Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors: Mototsugu
authors: M
authors: Nagao
authors: Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors: Hitoshi
authors: H
authors: Sugihara
authors: Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
authors: Shinichi
authors: S
authors: Oikawa
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D004036:Diet, Atherogenic / Q000009:adverse effects; D005260:Female; D005786:Gene Expression Regulation; D005947:Glucose / Q000008:administration & dosage; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008810:Mice, Inbred C57BL; D012850:Sinus of Valsalva / Q000378:metabolism / Q000473:pathology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D005947:Glucose