BACKGROUND/OBJECTIVES: Cholecystokinin (CCK), a hormone or neuropeptide, is secreted in response to intraluminal nutrients by enteroendocrine I-cells of the intestine and has important physiological actions related to appetite regulation and satiety. The stimulation on CCK secretion from the intestine is of potential relevance for body weight management. Naringenin (4',5,7-trihydroxyflavanone) and its glycoside naringin (naringenin 7-rhamnoglucoside) have been reported to have many biological functions. In the current study, we investigated the question of whether naringenin and naringin could stimulate CCK secretion and then examined the mechanisms involved in CCK release. MATERIALS/METHODS: STC-1 cells were used as a model of enteroendocrine cells. CCK release and changes in intracellular Ca2+ ([Ca2+]i) were measured after incubation of cells with naringenin and naringin for 1 h. RESULTS: Naringenin caused significant (P < 0.05) stimulation of CCK secretion, but naringin did not. In addition, regarding the secretory mechanisms, naringenin-induced CCK secretion involved increases in [Ca2+]i, influx of extracellular Ca2+, at least in part, and activation of TRP channels, including TRPA1. CONCLUSION: Findings of this study suggest that naringenin could have a role in appetite regulation and satiety.
Appetite ; Appetite Regulation ; Body Weight ; Cholecystokinin* ; Enteroendocrine Cells ; Intestines ; Neuropeptides

Hesperetin (3',5,7-trihydroxy 4'-methoxyflavanone) and its glycoside hesperidin (hesperetin 7-rhamnoglucoside) in oranges have been reported to possess pharmacological effects related to anti-obesity. However, hesperetin and hesperidin have not been studied on suppressive effects on appetite. This study examined that hesperetin and hesperidin can stimulate the release of cholecystokinin (CCK), one of appetite-regulating hormones, from the enteroendocrine STC-1 cells, and then examined the mechanisms involved in the CCK release. Hesperetin significantly and dose-dependently stimulated CCK secretion with an EC50 of 0.050 mM and increased the intracellular Ca2+ concentrations ([Ca2+]i) compared to the untreated control. The stimulatory effect by hesperetin was mediated via the entry of extracellular Ca2+ and the activation of TRP channels including TRPA1. These results suggest that hesperetin can be a candidate biomolecule for the suppression of appetite and eventually for the therapeutics of obesity.
Appetite ; Cholecystokinin* ; Citrus sinensis ; Enteroendocrine Cells ; Hesperidin ; Obesity

Incretin hormones are produced by enteroendocrine cells (EECs) in the intestine in response to ingested nutrient stimuli. The incretin effect is defined as the difference in the insulin secretory response between the oral glucose tolerance test and an isoglycemic intravenous glucose infusion study. The pathophysiology of the decreased incretin effect has been studied as decreased incretin sensitivity and/or β-cell dysfunction per se. Interestingly, robust increases in endogenous incretin secretion have been observed in many types of metabolic/bariatric surgery. Therefore, metabolic/bariatric surgery has been extensively studied for incretin physiology, not only the hormones themselves but also alterations in EECs distribution and genetic expression levels of gut hormones. These efforts have given us an enormous understanding of incretin biology from synthesis to in vivo behavior. Further innovative studies are needed to determine the mechanisms and targets of incretin hormones.
Bariatric Surgery ; Biology ; Enteroendocrine Cells ; European Union ; Glucose ; Glucose Tolerance Test ; Incretins* ; Insulin ; Intestines* ; Physiology

Ingestion of food affects secretion of hormones from enteroendocrine cells located in the gastrointestinal mucosa. These hormones are involved in the regulation of various gastrointestinal functions including the control of food intake. One cell in the stomach, the X/A-like has received much attention over the past years due to the production of ghrelin. Until now, ghrelin is the only known orexigenic hormone that is peripherally produced and centrally acting to stimulate food intake. Subsequently, additional peptide products of this cell have been described including desacyl ghrelin, obestatin and nesfatin-1. Desacyl ghrelin seems to be involved in the regulation of food intake as well and could play a counter-balancing role of ghrelin's orexigenic effect. In contrast, the initially proposed anorexigenic action of obestatin did not hold true and therefore the involvement of this peptide in the regulation of feeding is questionable. Lastly, the identification of nesfatin-1 in the same cell in different vesicles than ghrelin extended the function of this cell type to the inhibition of feeding. Therefore, this X/A-like cell could play a unique role by encompassing yin and yang properties to mediate not only hunger but also satiety.
Calcium-Binding Proteins ; DNA-Binding Proteins ; Eating ; Enteroendocrine Cells ; Ghrelin ; Hunger ; Mucous Membrane ; Nerve Tissue Proteins ; Obesity ; Stomach

The gastric epithelium is continuously regenerated by gastric stem cells, which give rise to various kinds of daughter cells, including parietal cells, chief cells, surface mucous cells, mucous neck cells, and enteroendocrine cells. The self-renewal and differentiation of gastric stem cells need delicate regulation to maintain the normal physiology of the stomach. Recently, it was hypothesized that cancer stem cells drive the cancer growth and metastasis. In contrast to conventional clonal evolution hypothesis, only cancer stem cells can initiate tumor formation, self-renew, and differentiate into various kinds of daughter cells. Because gastric cancer can originate from gastric stem cells and their self-renewal mechanism can be used by gastric cancer stem cells, we review here how critical signaling pathways, including hedgehog, Wnt, Notch, epidermal growth factor, and bone morphogenetic protein signaling, may regulate the self-renewal and differentiation of gastric stem cells and gastric cancer stem cells. In addition, the precancerous change of the gastric epithelium and the status of isolating gastric cancer stem cells from patients are reviewed.
Bone Morphogenetic Proteins ; Cell Differentiation ; Clonal Evolution ; Enteroendocrine Cells ; Epidermal Growth Factor ; Epithelium ; Hedgehogs ; Humans ; Neck ; Neoplasm Metastasis ; Neoplastic Stem Cells ; Nuclear Family ; Stem Cells ; Stomach ; Stomach Neoplasms

Recent findings indicate that Type 2 taste receptors (T2Rs) are expressed outside the gustatory system, including in the gastrointestinal tracts and the exocrine glands, such as the submandibular (SM), parotid (P), lacrimal (L) glands and pancreas (PC). Specifically, T2Rs are found in some of the gastrointestinal endocrine cells, and these cells secreted peptide hormones in response to stimulation by bitter-tasting compounds. The results show that T2Rs may have significant physiological roles besides bitter taste reception. The functions of the T2Rs in the exocrine glands remain poorly understood. An expression levels analysis of T2Rs will help to determine those functions in the exocrine glands. The expression levels of the T2Rs in the exocrine glands were discovered via the qPCR. C57BL/6J mice of 42~60-day-old were used. Messenger RNAs were extracted from S, P, L and PC. Cloned DNAs were synthesized by reverse transcription. Quantitative PCRs were performed using the SYBR Green method. The expression levels of the T2Rs were calculated as relative expression levels to that of the GAPDH. The statistical significance among the observed exocrine glands was tested using the variance analysis (ANOVA test). Tas2r108, out of murine 35 T2Rs, was the most highly expressed in every observed exocrine gland. This finding was similar to previous results from tongue papillae, but the expression levels were lower than those of the tongue papillae. Tas2r137 of SM, P, L and PC were expressed a little lower than that of tongue papillae. The T2Rs in the exocrine glands may play slightly different roles from those in the tongue. We suggest that physiological studies such as a patch clamp and functional Ca²⁺ imaging of acinar cells are necessary for understanding the Tas2r108 functions.
Acinar Cells ; Animals ; Clone Cells ; DNA ; Enteroendocrine Cells ; Exocrine Glands ; Gastrointestinal Tract ; Methods ; Mice ; Pancreas ; Peptide Hormones ; Polymerase Chain Reaction ; Reverse Transcription ; RNA, Messenger ; Tongue

The incretin hormones glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have recently received much attention for their roles in type 2 diabetes therapy. GLP-1 stimulated insulin secretion in a glucose-dependent manner and is secreted by intestinal L cells. It also regulates blood glucose concentration, stomach motility, appetite, and body weight. These actions are mediated through G-protein-coupled receptors highly expressed on pancreatic beta cells and also exert indirect metabolic actions. Activation of GLP-1 receptors also produces nonglycemic effects in various tissues. The pleiotropic effects of GLP-1 have been recently reported. The mechanisms identified in preclinical studies have potential translational relevance for the treatment of disease. Here, the nonglycemic effects of GLP-1, especially those on the liver, central nervous system, and bone, were reviewed.
Appetite ; Blood Glucose ; Body Weight ; Central Nervous System ; Enteroendocrine Cells ; Glucagon ; Glucagon-Like Peptide 1 ; Incretins ; Insulin ; Insulin-Secreting Cells ; Liver ; Receptors, G-Protein-Coupled ; Stomach

The regional distributions and frequencies of argyrophil endocrine cells in gastrointestinal (GI) tract of Balb/c-nu/ nu mouse were studied using Grimelius silver stain after abdominal subcutaneous implantation of COLO205. The experimental animals were divided into two groups, one is non-implanted group (Sham) and the other is COLO205-implanted group. Samples were collected from GI tract (fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum) at 21 days after implantation of COLO205 cells (1x10(6) cell/mouse). In this study, argyrophil cells were detected throughout the entire GI tract with various frequencies regardless of implantation. Most of these argyrophil cells in the mucosa of GI tract were generally spherical or spindle in shape (open type cell) while cells showing round in shape (close type cell) were found occasionally in gastric and/or intestinal gland regions. The regional distributions of argyrophil cells in COLO205 were similar to those of Sham. However, significant decreases of argyrophil cells were detected in COLO205 compared to those of Sham except for the jejunum and ileum. In the jejunum and ileum, argyrophil cells in COLO205 showed similar frequencies compared to those of Sham. In the pylorus, the most dramatically decreasement of argyrophil cells were detected in COLO205 compared to that of Sham. Implantation of COLO205 tumor cell line induced severe quantitative changes of argyrophil cell density, and the abnormality in density of GI endocrine cells may contribute to the development of gastrointestinal symptoms such as anorexia and indigestion, frequently encountered in patients with cancer.
Animals ; Cell Line, Tumor ; Colonic Neoplasms/*ultrastructure ; Enteroendocrine Cells/*ultrastructure ; Female ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Silver Staining

The sweet taste receptor is expressed in taste cells located in taste buds of the tongue. This receptor senses sweet substances in the oral cavity, activates taste cells, and transmits the taste signals to adjacent neurons. The sweet taste receptor is a heterodimer of two G protein-coupled receptors, T1R2 and T1R3. Recent studies have shown that this receptor is also expressed in the extragustatory system, including the gastrointestinal tract, pancreatic beta-cells, and glucose-responsive neurons in the brain. In the intestine, the sweet taste receptor regulates secretion of incretin hormones and glucose uptake from the lumen. In beta-cells, activation of the sweet taste receptor leads to stimulation of insulin secretion. Collectively, the sweet taste receptor plays an important role in recognition and metabolism of energy sources in the body.
Brain ; Calcium ; Cyclic AMP ; Enteroendocrine Cells ; Gastric Inhibitory Polypeptide ; Gastrointestinal Tract ; Glucagon-Like Peptide 1 ; Glucose ; Glucose Transport Proteins, Facilitative ; Incretins ; Insulin ; Intestines ; Mouth ; Neurons ; Taste Buds ; Tongue

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