Effects of Insulin and High Glucose on Human Meibomian Gland Epithelial Cells
Effects of Insulin and High Glucose on Human Meibomian Gland Epithelial Cells
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DOI：
10.1167/iovs.15-18049
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发表时间：
2015-12-01
影响因子：
4.4
通讯作者：
Sullivan, David A.
中科院分区：
文献类型：
--
作者：
Ding, Juan;Liu, Yang;Sullivan, David A.
目的。2型糖尿病是汗腺功能障碍(MGD)的危险因素。我们推测，糖尿病的影响至少部分归因于胰岛素抵抗/缺乏和高血糖对人类眉板腺上皮细胞(HMGECs)的影响。为了验证这一假设，我们研究了胰岛素和高糖是否会影响永生化的HMGEC。方法：将永生化的HMGEC培养在有血清或无血清的培养液中，并用胰岛素、胰岛素样生长因子-1(IGF-1)、IGF-1受体(R)封闭抗体以及葡萄糖或甘露醇处理不同时间。结果：胰岛素诱导IHMGECs磷脂酰肌醇3-激酶/Akt(AKT)信号通路呈剂量依赖性增加。这种作用涉及IGF-1R，但不涉及胰岛素受体(IR)，并与刺激细胞增殖和中性脂质积累有关。相反，高糖暴露改变了IHMGEC的细胞形态，导致进行性细胞丢失，并显著降低IGF-1R、磷酸化(P)-AKT、Foxhead box蛋白O1(FOXO1)和类固醇调节元件结合蛋白(SREBP-1)的水平。结论我们的数据表明，胰岛素刺激IHMGEC，而高糖对IHMGEC有毒性。这些结果支持我们的假设，即胰岛素抵抗/缺乏和高血糖对HMGEC有害，并可能有助于解释为什么II型糖尿病是MGD的危险因素。
PURPOSE. Type 2 diabetes is a risk factor for meibomian gland dysfunction (MGD). We hypothesize that this diabetic impact is due, at least in part, to the effects of insulin resistance/deficiency and hyperglycemia on human meibomian gland epithelial cells (HMGECs). To begin to test this hypothesis, we examined whether insulin and high glucose influence immortalized (I) HMGECs.METHODS. Immortalized HMGECs were cultured in serum-containing or -free media and treated with insulin, insulin-like growth factor-1 (IGF-1), IGF-1 receptor (R) blocking antibody, and glucose or mannitol for varying time periods. Specific proteins were detected by Western blots, cell proliferation was evaluated by manual cell counting and lipids were assessed with LipidTOX and high performance thin layer chromatography.RESULTS. We found that insulin induces a dose-dependent increase in phosphatidylinositide 3-kinase/Akt (AKT) signaling in IHMGECs. This effect involves the IGF-1R, but not the insulin receptor (IR), and is associated with a stimulation of cell proliferation and neutral lipid accumulation. In contrast, high glucose exposure alters cell morphology, causes a progressive cell loss, and significantly reduces the levels of IGF-1R, phospho (p)-AKT, Foxhead box protein O1 (FOXO1), and sterol-regulatory element binding protein (SREBP-1) in IHMGECs.CONCLUSIONS. Our data show that insulin stimulates, and that high glucose is toxic for, IHMGECs. These results support our hypothesis that insulin resistance/deficiency and hyperglycemia are deleterious for HMGECs and may help explain why type II diabetes is a risk factor for MGD.