Targeting our second brain to fight diabetes

The enteric nervous system (ENS) plays a key role in controlling the gut-brain axis under normal and pathological conditions, such as type 2 diabetes. The discovery of intestinal actors, such as enterosynes, able to modulate the ENS-induced duodenal contraction is considered a pioneering approach.

Objective: Decreasing duodenal contraction is now considered as a major focus for the treatment of type 2 diabetes.

Therefore, identifying bioactive molecules able to target the enteric nervous system, which controls the motility of intestinal smooth muscle cells, represents a new therapeutic avenue. For this reason, we chose to study the impact of oral galanin on this system in diabetic mice.

Methods: Enteric neurotransmission, duodenal contraction, glucose absorption, modification of gut-brain axis, and glucose metabolism (glucose tolerance, insulinemia, glucose entry in tissue, hepatic glucose metabolism) were assessed.

Results: We show that galanin, a neuropeptide expressed in the small intestine, decreases duodenal contraction by stimulating nitric oxide release from enteric neurons. This is associated with modification of hypothalamic nitric oxide release that favors glucose uptake in metabolic tissues such as skeletal muscle, liver, and adipose tissue. Oral chronic gavage with galanin in diabetic mice increases insulin sensitivity, which is associated with an improvement of several metabolic parameters such as glucose tolerance, fasting blood glucose, and insulin.

Conclusion: Here, we demonstrate that oral galanin administration improves glucose homeostasis via the enteric nervous system and could be considered a therapeutic potential for the treatment of T2D.

Source : Abot A, Lucas A, Bautzova T, Bessac A, Fournel A, Le-Gonidec S, Valet P, Moro C, Cani PD, Knauf C. Galanin enhances systemic glucose metabolism through enteric Nitric Oxide Synthase-expressed neurons. Mol Metab. 2018 Apr;10:100-108. doi: 10.1016/j.molmet.2018.01.020. Epub 2018 Jan 31. PMID: 29428595; PMCID: PMC5985240.

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