Insulin mediates de novo nuclear accumulation of the IGF-1/insulin Hybrid Receptor in corneal epithelial cells

Rossella Titone, Meifang Zhu, Danielle M. Robertson

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Insulin and insulin-like growth factor-1 (IGF-1) are present in human tears and likely play an important role in mediating ocular surface homeostasis. We previously characterized the IGF-1/insulin hybrid receptor (Hybrid-R) in corneal epithelial cells and found that it was activated by IGF-1 and not insulin; and reported the novel finding that it localized to the corneal epithelial cell nucleus. Since the corneal epithelium is an insulin insensitive tissue and does not require insulin for glucose uptake, this study investigated the function of insulin in corneal epithelial cells. We show that stress induced by growth factor deprivation triggers transcriptional upregulation and de novo nuclear accumulation of Hybrid-R through the homodimeric insulin receptor (INSR). This occurs independent of PI3K/Akt signaling. Nuclear accumulation of Hybrid-R was associated with partial cell cycle arrest and a corresponding reduction in mitochondrial respiration. Treatment with insulin, and not IGF-1, attenuated IGF-1R and INSR transcription and restored cell cycle and metabolic homeostasis. Together, these findings support that insulin mediates receptor homeostasis in corneal epithelial cells, favoring an IGF-1 mediated pathway. This may have important implications in diabetic corneal disease and wound healing.

Original languageEnglish (US)
Article number4378
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Insulin Receptor
Somatomedins
Epithelial Cells
Insulin
Homeostasis
Corneal Diseases
Corneal Epithelium
Cell Cycle Checkpoints
Cell Nucleus
Tears
Phosphatidylinositol 3-Kinases
Insulin-Like Growth Factor I
Wound Healing
Intercellular Signaling Peptides and Proteins
Cell Cycle
Respiration
Up-Regulation
Glucose

ASJC Scopus subject areas

  • General

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Insulin mediates de novo nuclear accumulation of the IGF-1/insulin Hybrid Receptor in corneal epithelial cells. / Titone, Rossella; Zhu, Meifang; Robertson, Danielle M.

In: Scientific Reports, Vol. 8, No. 1, 4378, 01.12.2018.

Research output: Contribution to journalArticle

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