Variation in Type 2 Diabetes-Related Phenotypes among Apolipoprotein E-Deficient Mouse Strains

PLoS One. 2015 May 6;10(5):e0120935. doi: 10.1371/journal.pone.0120935. eCollection 2015.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology
  • Genetic Variation*
  • Insulin Resistance
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Phenotype*

Substances

  • Apolipoproteins E
  • Blood Glucose