Elsevier

Molecular Metabolism

Volume 10, April 2018, Pages 100-108
Molecular Metabolism

Brief Communication
Galanin enhances systemic glucose metabolism through enteric Nitric Oxide Synthase-expressed neurons

https://doi.org/10.1016/j.molmet.2018.01.020Get rights and content
Under a Creative Commons license
open access

Highlights

  • Targeting the enteric nervous system (ENS) is an innovative solution to treat diabetes.

  • The ENS controls duodenal contractions to modulate glycemia via the gut–brain axis.

  • ENS/contractions are targeted by the neuropeptide galanin in the intestine.

  • Oral galanin treatment decreases duodenal hyper-contractility in diabetic mice.

  • Oral galanin restores the gut–brain axis to improve glycemia in diabetic mice.

Abstract

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.

Keywords

Galanin
Enteric nervous system
Diabetes

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