Effects of Insulin and High Glucose on Human Meibomian Gland Epithelial Cells

Invest Ophthalmol Vis Sci. 2015 Dec;56(13):7814-20. doi: 10.1167/iovs.15-18049.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Count
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Dose-Response Relationship, Drug
  • Dry Eye Syndromes / drug therapy*
  • Dry Eye Syndromes / metabolism
  • Dry Eye Syndromes / physiopathology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Glucose / administration & dosage
  • Glucose / adverse effects*
  • Glucose / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / pharmacology*
  • Insulin / administration & dosage
  • Insulin / metabolism
  • Insulin / pharmacology*
  • Lipid Metabolism / drug effects
  • Lysosomes / metabolism
  • Meibomian Glands / cytology*
  • Signal Transduction / drug effects

Substances

  • Hypoglycemic Agents
  • Insulin
  • Glucose