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Insulin's role in recovering the sense of smell

Research investigates the role of insulin in olfactory neuron regeneration
Researchers in Tokyo and Philadelphia have been exploring the role of insulin in the regeneration of olfactory sensory neurons.

Olfactory sensory neurons (OSNs) are the receptors that carry the signal of a smell to the brain. When a virus attacks, these neurons are damaged and can die off, which affects the patient’s ability to smell. This is the case for many people who are still without smell many months after Covid-19. Fortunately, olfactory neurons regenerate to a certain extent and the sense of smell will improve, but this healing process can take time.

The research team followed a hunch that insulin was involved in the regeneration of OSNs. They studied the regeneration of neurons in two groups of mice; one diabetic group (not producing insulin), and a healthy control group that produced insulin naturally.

They observed that for the first 14 days the olfactory sensory neurons regenerated at a similar rate in both groups of mice. A difference in recovery started to become apparent after day 14. 

Compared to the healthy control group, after day 14 the diabetic mice were found to have

  • fewer mature olfactory sensory neurons, 

  • more neurons dying off naturally

  • lower responses in the areas of the brain stimulated by smell

  • less reaction to smell registering in their olfactory bulbs, and

  • performed worse in a task that required them to sniff out food.

Noticing that a lack of insulin was preventing the recovery of smell, the researchers tried injecting insulin into the nose of the diabetic mice to see if that would help recovery. If insulin was administered during day 8 to 13, the diabetic mice showed similar recovery rates to the normal group. Insulin given before day 7 didn’t make a difference, the critical time window was in the second week of recovery.

Interestingly, the healthy control group of mice benefited from insulin too.

From this research, the team concluded that insulin is important in the regeneration of olfactory sensory neurons, and the second week of recovery is particularly important in the process. 

What this means for treatment

This study is in mice, so a long way from being considered suitable for human treatment. However, by identifying the importance of insulin in the regeneration process scientists are another step forward in understanding what happens when smell is lost after a viral infection, and some of the factors that are involved in recovery. 

Each small step forward brings us closer to potential treatments in the future.


This paper is published in New Research, Sensory and Motor Systems

Insulin-dependent maturation of newly generated olfactory sensory neurons after injury

Akihito Kuboki, Shu Kikuta, Nobuyoshi Otori, Hiromi Kojima, Ichiro Matsumoto, Johannes Reisert and Tatsuya Yamasoba 

Cite as: eNeuro 2021; 10.1523/ENEURO.0168-21.2021

May 20, 2021