Insulin but not leptin protects olfactory mucosa from apoptosis

J Neuroendocrinol. 2011 Jul;23(7):627-40. doi: 10.1111/j.1365-2826.2011.02154.x.


The mammalian olfactory mucosa (OM) is continually renewed throughout life. Owing to their position in the nasal cavity, OM cells are exposed to multiple insults, including high levels of odourants that can induce their death. OM regeneration is therefore essential to maintain olfactory function, and requires the tight control of both cell death and proliferation. Apoptosis has been implicated in OM cell death. Olfaction is one of the senses involved in food intake and depends on individual nutritional status. We have previously reported the influence of hormones related to nutritional status on odour perception and have shown that the OM is a target of insulin and leptin, two hormones known for their anti-apoptotic properties. In the present study, we investigated the potential anti-apoptotic effect of these metabolic hormones on OM cells. Both Odora cells (an olfactive cell line) and OM cells treated with etoposide, a p53 activity inducer, exhibited mitochondrial-dependent apoptosis that was inhibited by the pan-caspase inhibitor zVAD-fmk. Insulin, but not leptin, impaired this apoptotic effect. Insulin addition to the culture medium reduced p53 phosphorylation, caspase-3 and caspase-9 cleavage, and caspase-3 enzymatic activity induced by etoposide. The apoptotic wave observed in the OM after interruption of the neuronal connections between the OM and the olfactory bulb by bulbectomy was impaired by intranasal insulin treatment. These findings suggest that insulin may be involved in OM cellular dynamics, through endocrine and/or paracrine-autocrine effects of circulating or local insulin, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects*
  • Cells, Cultured
  • Culture Media, Serum-Free / pharmacology
  • Cytoprotection / drug effects
  • Down-Regulation / drug effects
  • Drug Evaluation, Preclinical
  • Etoposide / pharmacology
  • Insulin / pharmacology*
  • Leptin / pharmacology*
  • Male
  • Olfactory Mucosa / drug effects*
  • Olfactory Mucosa / physiology
  • Rats
  • Rats, Wistar


  • Antineoplastic Agents, Phytogenic
  • Culture Media, Serum-Free
  • Insulin
  • Leptin
  • Etoposide