Impact of Intestinal Peptides on the Enteric Nervous System: Novel Approaches to Control Glucose Metabolism and Food Intake

Abstract

The gut is one of the most important sources of bioactive peptides in the body. In addition to their direct actions in the brain and/or peripheral tissues, the intestinal peptides can also have an impact on enteric nervous neurons. By modifying the endogenousproduction of these peptides, one may expect modify the “local” physiology such as glucose absorption, but also could have a “global” action via the gut–brain axis. Due to the various origins of gut peptides (i.e., nutrients, intestinal wall, gut microbiota) and the heterogeneity of enteric neurons population, the potential physiological parameters control by the interaction between the two partners are multiple. In this review, we will exclusively focus on the role of enteric nervous system as a potential target of gut peptides to control glucose metabolism and food intake. Potential therapeutic strategies based on per os administration of gut peptides to treat type 2 diabetes will be described.

Physiological Effect of Ghrelin on Body Systems

“…IV or intracerebroventricular (ICV) administration of ghrelin affects not only gastrointestinal secretion but also motility [117]. Endogenous or peripheral administration of ghrelin to humans promotes gastric and small intestinal motility by stimulation of enteric cholinergic neurons with an additional role of serotonin [124][125][126]. Ghrelin, like motilin, promotes gastric emptying.…”

Inflammation and Gut-Brain Axis During Type 2 Diabetes: Focus on the Crosstalk Between Intestinal Immune Cells and Enteric Nervous System

“…The gut-brain axis is shown as a major signaling pathway controlling glucose homeostasis, and its disturbance is associated with a T2D phenotype ( Abot et al, 2018a , b ). In normal conditions, glucose is detected by intestinal glucose sensors (such as SGLT1, GLUT2, TASR1/2) present on intestinal cells (enteroendocrine and brush cells, enteric glial cells and neurons) which inform the whole body from the presence of glucose via the release of various factors (i.e., gut hormones, neurotransmitters, metabolites) ( Fournel et al, 2016 ).…”

“…Intestinal motility is regulated by ENS that includes intrinsic primary afferent neurons (IPAN), interneurons and choline acetyltransferase (ChAT)-producing excitatory and NO synthase (NOS)-producing inhibitory motor neurons ( Abot et al, 2018a ). In the context of immune-mediated regulation of intestinal motility, muscularis macrophages residing in the myenteric plexus have been largely studied ( Mikkelsen, 2010 ; Muller et al, 2014 ; De Schepper et al, 2017 ).…”

Intrapancreatic Ganglia and Neural Regulation of Pancreatic Endocrine Secretion

“…The role of enteric nerves in controlling the endocrine functions of the pancreas has not been completely elucidated. The ENS may be a therapeutic target for the regulation of glucose metabolism (Abot et al, 2018a,b).…”