Insulin-like growth factor 2 enhances insulinogenic differentiation of human eyelid adipose stem cells via the insulin receptor
Insulin-like growth factor 2 enhances insulinogenic differentiation of human eyelid adipose stem cells via the insulin receptor
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DOI：
10.1111/j.1365-2184.2011.00755.x
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发表时间：
2011-06-01
影响因子：
8.5
通讯作者：
Kim, H.
中科院分区：
文献类型：
--
作者：
Kang, H. M.;Park, S.;Kim, H.
目的：以前，我们已经从人眼睑脂肪组织中分离出干细胞（HEAC），并将其功能性分化为胰岛素分泌细胞。在本研究中，我们研究了胰岛素家族成员是否可能影响HEAC.Materials和方法的insulinogenic分化：在分化培养基中含有胰岛素家族成员或不，细胞的基因表达，蛋白质表达，特别是，胰岛素和C-肽的分泌，在高葡萄糖的挑战。使用针对特异性受体的抗体，靶受体介导的胰岛素家族成员的作用investigated.Results：胰岛素治疗在培养过程中对胰岛素或C-肽分泌HEAC，对高糖挑战培养后的影响不大。然而，胰岛素样生长因子（IGF）1治疗减少了这两种分泌，有趣的是，IGF 2大大增加了分泌。胰岛素样生长因子2处理的HEAC有较强的Pdx 1，Isl 1，Pax 6和PC 1/3基因表达，胰岛素和C肽抗体，双硫腙后有明显的染色。胰岛素样生长因子2增强的胰岛素原分化被胰岛素受体抗体（IR）完全阻断，但不被抗胰岛素样生长因子1受体（IGF 1 R）阻断。结论：IGF 1可能抑制HEAC的胰岛素原性分化，而IGF 2可能促进HEAC的胰岛素原性分化，且IGF 2的促进作用可能是通过IR介导的。
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.