Enteric neurons and glycemia control

gut brain

The gut-brain axis:
You have a message from your gut

In the intestine, gut distension and nutrients are detected by mechanoreceptors and chemoreceptors, respectively. The activation of these receptors sends an afferent nervous message to the hypothalamus in the brain. In turn, the hypothalamus controls the glucose entry in tissues, and thus glycemia.

The mechanism of action in type 2 diabetes

Alteration of ENS activity results in a duodenal hypercontractility that leads to hyperglycemia via 1) an increase of glucose levels during the post-prandial period, and 2) the sending of an aberrant nervous message to the hypothalamus that participates to insulin-resistance.

Targeting mechanosensing: a new hope to fight type 2 diabetes via the gut-brain axis

Future therapeutic strategies could be considered to decrease duodenal hyper-contractility in order to restore the gut-brain axis and stop the evolution of insulin-resistance. How can we decrease the activity of duodenal smooth muscle cells without side effects?

Using pharmacological approaches, the team of Pr. Claude Knauf discovered that bioactive peptides released by enterocytes (apelin) or by enteric neurons (galanin, enkephalin) could exert a benefic and stimulatory effect on neurons in the myenteric plexus. These neurons are known to decrease the contraction of smooth muscle cells. These preclinical studies also demonstrated that when duodenal contractions return to normal in diabetic mice, the hypothalamic activity is restored and is similar to that of non-diabetic mice. Specifically, the hypothalamic nitric oxide (NO) can again exert its beneficial effects on the Central Nervous System (CNS). Then, a nervous signal from the hypothalamus is sent to the tissues (skeletal muscle, adipose tissue, liver) to improve glucose sensibility and favor glucose entry. Hyperglycemia, which is deeply deleterious to the body, is therefore reduced.

In this complex mode of communication, the gut microbiota plays a key role. Indeed, researchers have shown that the gut microbiota can influence the production of some of the peptides cited above. Thus, a nutritional approach to restore it could be proposed in addition to classical pharmacological therapies.

Credits : Pr. Knauf




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