Insulin-like growth factor 2 enhances insulinogenic differentiation of human eyelid adipose stem cells via the insulin receptor

Objectives: Previously, we have isolated stem cells (HEAC) from human eyelid adipose tissue and functionally differentiated them into insulin-secreting cells. In the present study, we examined whether insulin family members might influence insulinogenic differentiation of HEAC. Materials and methods: Following culture in differentiation media containing insulin family member or not, cells were examined for gene expression, protein expression and, particularly, insulin and C-peptide secretion, in response to high glucose challenge. Using antibodies against the specific receptor, target receptor mediating effect of the insulin family member was investigated. Results: Insulin treatment during culture had little effect on either insulin or C-peptide secretion from HEAC, against high glucose challenge after culture. However, insulin-like growth factor (IGF) 1 treatment decreased both secretions, and interestingly, IGF2 greatly increased the secretions. HEAC treated with IGF2 had strong expression of Pdx1, Isl1, Pax6 and PC1/3 genes, and distinct staining after insulin and C-peptide antibodies, and dithizone. IGF2-enhanced insulinogenic differentiation was totally blocked by antibody against insulin receptor (IR), but not by anti-IGF1 receptor (IGF1R). Differentiated HEAC expressed both IR and IGF1R genes, whereas they expressed neither IGF2 nor IGF2R genes. Conclusions: From these results, it is suggested that IGF1 might inhibit insulinogenic differentiation of HEAC, whereas IGF2 enhances differentiation, and that enhancement of IGF2 appeared to be mediated via IR.