Insights from engraftable immunodeficient mouse models of hyperinsulinaemia

Hyperinsulinaemia, obesity and dyslipidaemia are independent and collective risk factors for many cancers. The long‐term effects of a 23% high fat diet (HFD) in two immunodeficient mouse strains (NOD/SCID and Rag1−/−), and the effect of diet‐induced hyperinsulinaemia on human prostate cancer cell line xenograft growth, were investigated. Rag1−/− and NOD/SCID HFD‐fed mice demonstrated diet‐induced impairments in glucose tolerance at 16 and 23 weeks post weaning. Rag1−/− mice developed significantly higher fasting insulin levels (2.16 ± 1.01 ng/mL, P = .01) and increased insulin resistance (6.70 ± 1.68 HOMA‐IR, P = .01) compared to normal chow‐fed controls (0.71 ± 0.12 ng/mL and 2.91 ± 0.42 HOMA‐IR), however, alterations in insulin resistance were not observed in the NOD/SCID strain...