Glucose, epithelium, and enteric nervous system: dialogue in the dark

Abstract

The gastrointestinal epithelium is in close contact with the various components of the chymus, including nutrients, bacteria and toxins. The epithelial barrier has to decide which components are effectively absorbed and which components are extruded. In the small intestine, a nutrient like glucose is mainly absorbed by the sodium linked glucose cotransporter 1 (SGLT1) and the glucose transporter 2 (GLUT2). The expression and activity of both transport proteins is directly linked to the amount of intraluminal glucose. Besides the direct interaction between glucose and the enterocytes, glucose also stimulates different sensory mechanisms within the intestinal wall. The most important types of cells involved in the sensing of intraluminal contents are enteroendocrine cells and neurones of the enteric nervous system. Regarding glucosensing, a distinct type of enteroendocrine cells, the enterochromaffine (EC) cells are involved. Excitation of EC cells by intraluminal glucose results in the release of serotonin (5-HT), which modulates epithelial functions and activates enteric secretomotorneurones. Enteric neurones are not only activated by 5-HT, but also directly by glucose. The activation of different cell types and the subsequent crosstalk between these cells may trigger appropriate absorptive and secretory processes within the intestine.

Gut glucose metabolism in rainbow trout: implications in glucose homeostasis and glucosensing capacity

“…Although the involvement of enteric neurons in the reception of luminal glucose might be indirect (38), glucose has been shown to directly influence the activity of enteric neurons in mammals, although the mechanism underlying this ability remains under debate. Ma and Kirchgessner (20) detected (as in the present study) transcripts for GLUT2, GK, and K ATP subunits in rat mucosa and enteric neurons.…”

“…In mammalian intestine, sensing of luminal glucose can be accomplished by different cell types (38), including enterocytes, enteroendocrine cells (K and L), and components of the enteric nervous system. The glucosensing ability in mammalian intestine includes key components of the pancreatic glucosensing system (36,44,45) and is involved in functions like GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion.…”

“…In mammals, glucose is the most important nutrient with regard to energy supply, and as in other tissues (45), glucosensing capacities also have been reported in GIT cells, including enterocytes, enteroendocrine cells, and enteric neurons (38). Although the mechanism remains to be fully elucidated, some of the actors involved in this function are most likely the same as those present in the glucosensing mechanism of pancreatic ␤-cells (45), such as glucokinase (GK) or ATP-dependent potassium channels (K ATP ), whereas others seem to be more GIT specific, such as sodium-dependent glucose transporters (SGLTs) (9,29).…”

Glucosensing in the gastrointestinal tract: Impact on glucose metabolism

“…The gut wall is composed of millions of neurons organized into two major plexus: the submucosal plexus, which is directly in contact with the intestinal mucosa, and the myenteric plexus, located between the circular and longitudinal muscular layers (73). Although the enteric nervous system (ENS) is classically known to control intestinal motility, secretion, and absorption, recent evidence suggests its involvement in glucosensing.…”

“…MECHANISM OF GLUCOSE DETECTION IN THE DIGESTIVE TRACT hormones stimulated by glucosensing EECs might be able to secondarily activate enteric neurons (73). Thus, activation of enteric neurons by intraluminal glucose occurs either directly or indirectly via the EECs.…”