Korean Diabetes J.  2009 Dec;33(6):458-463. 10.4093/kdj.2009.33.6.458.

Stimulation of Glucagon Like Peptide-1 Secretion in Enteroendocrine L cells

• Kim BJ

• KMID: 2298050
• DOI: http://doi.org/10.4093/kdj.2009.33.6.458

Abstract

GLP-1 (glucagon like peptide-1) is new anti-diabetic drug with a number of beneficial effects. It stimulates glucose dependant insulin secretion and restoration of beta cell mass through enhancement of islet mass. However, it is easily inactivated after being secreted from enteroendocrine L cells. Recent trial to increased GLP-1 is to directly stimulate L cells through its receptor located in the surface of L cell. Taste receptor in the apical surface of L cell is activated by various tastants contained in the food. Tongue perceives taste sense through the heterotrimeric G-protein (alpha-gustducin) and its downstream signaling cascades. Same taste receptors are also expressed in enteroendocrine cells. In duodenal L cell, alpha-gustducin was detected by immunofluorescence stainig at the luminal projections of enteroendocrine cells. And several other taste signaling elements were also found in L cells. Ingestion of sweet or bitter compounds revealed stimulation of GLP-1 secretion and the regulation of plasma insulin and glucose. In this review, I will briefly introduce the possibilities to stimulate GLP-1 secretion though the membrane receptor in enteroendocrine cell. And it will be the good candidate to develop the treatment modality for obesity, diabetes and abnormal gut motility.

Keyword

Enteroendocrine cells; Glucagon like peptide-1; Taste receptor

MeSH Terms

Eating
Enteroendocrine Cells
Fluorescent Antibody Technique
Glucagon
Glucagon-Like Peptide 1
Glucose
GTP-Binding Proteins
Insulin
Membranes
Obesity
Phenobarbital
Plasma
Tongue
Transducin
GTP-Binding Proteins
Glucagon
Glucagon-Like Peptide 1
Glucose
Insulin
Phenobarbital
Transducin

Figure

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  Fig. 1 Nutrient sensing by enteroendocrine cells. Luminal nutrients can act by 1 of 3 pathways. Nutrients can stimulate directly with receptors/transport proteins present in surface of endocrine cells (1). Nutrients can stimulate through intrinsic or extrinsic innervation after transported into adjacent epithelial cells (2) Nutrients can interact with sensing cells and then stimulate secretion with paracrine manner (3)4).

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  Fig. 2 Variable effects of TGR5 in intestinal L cells, hepatic sinusoidal endothelial cells and immune cells (monocyte, macrophage and hepatic kupffer cells) and metabolically relevant tissues9-11).

• 

  Fig. 3 A schematic figure of tastant-induced signaling via T2Rs and T1Rs in enteroendocrine cell engages α-gustducin, PLCβ2, TRPM5, and L-type VSCCs. Bitter and sweet receptor triggers the release of GI peptides into the basolateral portion of the cell22).

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