Sex difference of hyperinsulinemia in the C57BL/6J-Daruma (obese) mouse

Abstract

The C57BL/6J-Daruma mouse is an animal model of obesity derived from the original genetically obese ICR-Daruma mouse by transfer of the phenotype into the C57BL/6J background by backcrossing into the C57BL/6J strain. Although, like the original ICR-Daruma mouse model, both male and female C57BL/6J-Daruma mice develop obesity, the latter strain shows sex differences in several phenotypes. A sex difference in plasma insulin levels was especially notable in C57BL/6J-Daruma mice; only males showed hyperinsulinemia. Orchiectomy suppressed this hyperinsulinemia completely, whereas testosterone supplementation restored it. Glucose administration increased the plasma glucose level in both male and female Daruma mice to a greater extent than in wild-type control mice. Orchiectomy, but not ovariectomy, decreased the plasma glucose level to that seen in wild-type controls. On the other hand, this effect of orchiectomy was abrogated by testosterone supplementation. The expression of mRNAs for several genes related to insulin resistance was significantly changed in white adipose tissue and liver of C57BL/6J-Daruma mice, especially males, as early as 4 weeks of age. The present results suggest that testosterone may be involved in the hyperinsulinemia shown by male C57BL/6J-Daruma mice and that this strain may be an appropriate animal model for examining the relationship between obesity and sex hormones.