title: Effects of Insulin and High Glucose on Human Meibomian Gland Epithelial Cells.
abstract: OBJECTIVE
  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.
authors.forename: Juan
authors.initials: J
authors.lastname: Ding
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: David A
authors.initials: DA
authors.lastname: Sullivan
mesh_terms: D015153:Blotting, Western; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008247:Lysosomes / Q000378:metabolism; D008537:Meibomian Glands / Q000166:cytology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose