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.