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.