The phenomenal increase in type 2 diabetes in recent decades has inspired a rush to find drugs that could treat the condition, as well as attempts to address the underlying causes. The idea that stimulating a nerve could solve the problem seems almost too good to be true, yet the technique appears to work in rats, inspiring hope the same might be true for humans.
The nerve in question is the carotid sinus nerve, a relatively small and obscure nerve in the neck that connects to the very important vagus nerve.
Type 2 diabetes occurs when the body fails to produce enough insulin to regulate the consumption of sugar, or shows decreased response to insulin in the muscles and liver.
Diabetes has been seen as a malfunction in the pancreas, where insulin is produced, or in the parts of the body where the hormone does its work. However, in 2013 Dr Silvia Vilares Conde of CEDOC-NOVA Medical School in Portugal proved the carotid body, usually thought of as an oxygen sensor, also has a role, regulating the sensitivity to insulin in peripheral regions of the body. Any malfunction contributes to diabetes. The carotid sinus nerve, which connects to the carotid body, is overactive in animals with type 2 diabetes.
Conde showed that severing the carotid sinus nerve in diabetic rats, and so disconnecting the carotid body from the brain, restores insulin sensitivity and glucose tolerance.
As Conde now notes in Diabetologia, however, this is a rather drastic action. Not only is it irreversible, but the consequences can be severe. The nerve helps the body recognize a shortage of oxygen, and triggers faster breathing as a response. Without it, exercise could become dangerous as we might fail to take in the air we need.
A less permanent approach is to apply electrodes to down-modulate the nerve’s activity. When Conde tried this using electrical stimulation operating at kilohertz frequencies, she observed not only a decrease in type 2 diabetes symptoms in the rats, without severe side effects, but also that the process was reversible when stimulation ceased.
“This work opens the door to the development of a new therapeutic for type 2 diabetes that will provide a long-term management of the disease with negligible adverse effects and interference with daily activities,” Conde said in a statement.
At lower frequencies, even while modulation was occurring, the rats treated in this way increased their breath rate during exercise, unlike those whose nerve had been severed. However, above 50 kHz respiration rates did not increase during exercise, indicating any treatment would need to use carefully calibrated frequencies to prevent oxygen depletion.