title: Variation in Type 2 Diabetes-Related Phenotypes among Apolipoprotein E-Deficient Mouse Strains.
abstract: We recently have found that apolipoprotein E-deficient (Apoe(-/-)) mice with the C57BL/6 background develop type 2 diabetes when fed a Western diet for 12 weeks. In the present study we constructed multiple Apoe(-/-) mouse strains to find diabetes-related phenotyptic variations that might be linked to atherosclerosis development. Evaluation of both early and advanced lesion formation in aortic root revealed that C57BL/6, SWR/J, and SM/J Apoe(-/-) mice were susceptible to atherosclerosis and that C3H/HeJ and BALB/cJ Apoe(-/-) mice were relatively resistant. On a chow diet, fasting plasma glucose varied among strains with C3H/HeJ having the highest (171.1 ± 9.7 mg/dl) and BALB/cJ the lowest level (104.0 ± 6.6 mg/dl). On a Western diet, fasting plasma glucose rose significantly in all strains, with C57BL/6, C3H/HeJ and SWR/J exceeding 250 mg/dl. BALB/cJ and C3H/HeJ were more tolerant to glucose loading than the other 3 strains. C57BL/6 was sensitive to insulin while other strains were not. Non-fasting blood glucose was significantly lower in C3H/HeJ and BALB/cJ than C57BL/6, SM/J, and SWR/J. Glucose loading induced the 1st and the 2nd phase of insulin secretion in BALB/cJ, but the 2nd phase was not observed in other strains. Morphological analysis showed that BALB/cJ had the largest islet area (1,421,493 ± 61,244 μm(2)) and C57BL/6 had the smallest one (747,635 ± 41,798 μm(2)). This study has demonstrated strain-specific variations in the metabolic and atherosclerotic phenotypes, thus laying the basis for future genetic characterization.
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Shuiping
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Mei-Hua
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Zhenqi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, Virginia, United States of America; Biochemistry & Molecular Genetics, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Weibin
authors.initials: W
authors.lastname: Shi
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D014644:Genetic Variation; D007333:Insulin Resistance; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose