Examined in either males or females, β-cell mass was not different between control and knockout mice, indicating a possible defect in β-cell function as underlying the glucose dyshomeostasis reported above. Correspondingly, clear tendencies were apparent toward impaired β-cell function and lowered insulin levels when one combined fasting glycemia with corresponding insulin plasma concentration using HOMA2 analysis (particularly in females; Fig. 7, E and G). According to this analysis, insulin sensitivity was slightly but significantly increased in knockout females vs. littermate controls (Fig. 7H), again indicating that a defect in β-cell function is likely to underlie the mild glucose intolerance in knockout mice (and subject to caveats in extrapolating HOMA2 models from humans to rodents) (74).