title: Detection and signaling of glucose in the intestinal mucosa--vagal pathway.
abstract: Intestinal luminal exposure to glucose initiates changes in food intake and gastrointestinal (GI) motor and secretory function. It does this by stimulating the release of GI hormones and 5-hydroxytryptamine (5-HT) from enteroendocrine and enterochromaffin cells (EC), respectively, which in turn activate intrinsic and extrinsic neuronal pathways. An article in this issue of the journal provides new insight into the mechanisms involved in luminal glucose sensing. Vincent et al. have used a novel in vivo technique to determine activation of gut epithelial cells and vagal afferent pathways in rats by staining for activated calcium-calmodulin kinase II (pCaMKII) along the pathway. In the mucosa, they found that intraluminal glucose activated EC cells and brush cells. At the next stage, pCaMKII was seen in neurons of the myenteric plexus and vagal afferent neurons in the nodose ganglia. In the central nervous system (CNS), activation was seen in second- and higher-order neurons in the dorsal vagal complex and hypothalamus. They found that 5-HT(3) receptors were involved in initiating neural signaling as activation of neurons, but not EC cells, was reduced by 5-HT(3) receptor antagonism. Selectively stimulating the sodium-glucose cotransporter (SGLT-3) had similar effects to glucose. This suggests that SGLT-3 behaves as a glucose sensor, mainly on EC cells, inducing the release of 5-HT, which activates 5-HT(3) receptors on vagal afferent endings nearby and in turn, their connections in the CNS. There is evidence elsewhere that other sensors and transmitter mechanisms are involved in this pathway, so the possibility exists of multiple redundant systems.
authors.affiliation: Nerve-Gut Research Laboratory, Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia. ashley.blackshaw@adelaide.edu.au
authors.forename: L
authors.initials: L
authors.lastname: Ashley Blackshaw
authors.forename: R L
authors.initials: RL
authors.lastname: Young
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology*; D003243:Consciousness / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000502:physiology*; D008297:Male; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D005947:Glucose