scholarly journals Human Intestinal Enteroids With Inducible Neurogenin-3 Expression as a Novel Model of Gut Hormone Secretion

2019 ◽  
Vol 8 (2) ◽  
pp. 209-229 ◽  
Author(s):  
Alexandra L. Chang-Graham ◽  
Heather A. Danhof ◽  
Melinda A. Engevik ◽  
Catherine Tomaro-Duchesneau ◽  
Umesh C. Karandikar ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Neurogenin 3 ◽  
Gut Hormone ◽  
Novel Model

scholarly journals Human intestinal enteroids with inducible neurogenin-3 expression as a novel model of gut hormone secretion

2019 ◽  
Author(s):  
Alexandra L. Chang-Graham ◽  
Heather A. Danhof ◽  
Melinda A. Engevik ◽  
Catherine Tomaro-Duchesneau ◽  
Umesh C. Karandikar ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Cell Types ◽  
Inducible Expression ◽  
Enteroendocrine Cells ◽  
Neurogenin 3 ◽  
Rotavirus Infection ◽  
Functional Studies ◽  
Gut Hormone ◽  
The Impact

AbstractBackgroundEnteroendocrine cells (EECs) are specialized epithelial cells that produce molecules vital for intestinal homeostasis, but due to their limited numbers, in-depth functional studies have remained challenging. Human intestinal enteroids (HIEs) that are derived from intestinal crypt stem cells are a biologically relevantin vitromodel of the intestinal epithelium. HIEs contain all intestinal epithelial cell types; however, like the intestine, HIEs spontaneously produce few EECs, which limits their study.MethodsTo increase the number of EECs in HIEs, we used lentivirus transduction to stably engineer jejunal HIEs with doxycycline-inducible expression of neurogenin-3 (NGN3), a transcription factor that drives EEC differentiation (tetNGN3-HIEs). We examined the impact ofNGN3induction on EECs by quantifying the increase in the enterochromaffin cells and other EEC subtypes. We functionally assessed secretion of serotonin and EEC hormones in response to norepinephrine and rotavirus infection.ResultsTreating tetNGN3-HIEs with doxycycline induced a dose-dependent increase of chromogranin A (ChgA)-positive and serotonin-positive cells, demonstrating increased enterochromaffin cell differentiation. Despite increased ChgA-positive cells, other differentiated cell types of the epithelium remained largely unchanged by gene expression and immunostaining. RNA sequencing of doxycycline-induced tetNGN3- HIEs identified increased expression of key hormones and enzymes associated with several other EEC subtypes. Doxycycline-induced tetNGN3-HIEs secreted serotonin, monocyte chemoattractant protein-1, glucose-dependent insulinotropic peptide, peptide YY, and ghrelin in response to norepinephrine and rotavirus infection, further supporting the presence of multiple EEC types.ConclusionsWe have combined HIEs and inducible-NGN3expression to establish a flexiblein vitromodel system for functional studies of EECs in enteroids and advance the molecular and physiological investigation of EECs.SynopsisEnteroendocrine cells have low abundance but exert widespread effects on gastrointestinal physiology. We engineered human intestinal enteroids with inducible expression of neurogenin-3, resulting in increased enteroendocrine cells and facilitating investigations of host responses to the dynamic intestinal environment.

scholarly journals Effect of the Natural Sweetener Xylitol on Gut Hormone Secretion and Gastric Emptying in Humans: A Pilot Dose-Ranging Study

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 174
Author(s):  
Anne Christin Meyer-Gerspach ◽  
Jürgen Drewe ◽  
Wout Verbeure ◽  
Carel W. le Roux ◽  
Ludmilla Dellatorre-Teixeira ◽  
...  
Keyword(s):  
Uric Acid ◽  
Gastric Emptying ◽  
Blood Lipids ◽  
Tap Water ◽  
Hormone Secretion ◽  
Gastrointestinal Symptoms ◽  
Gut Hormones ◽  
Double Blind ◽  
Gut Hormone ◽  
Dose Dependent

Sugar consumption is associated with a whole range of negative health effects and should be reduced and the natural sweetener xylitol might be helpful in achieving this goal. The present study was conducted as a randomized, placebo-controlled, double-blind, cross-over trial. Twelve healthy, lean volunteers received intragastric solutions with 7, 17 or 35 g xylitol or tap water on four separate days. We examined effects on: gut hormones, glucose, insulin, glucagon, uric acid, lipid profile, as well as gastric emptying rates, appetite-related sensations and gastrointestinal symptoms. We found: (i) a dose-dependent stimulation of cholecystokinin (CCK), active glucagon-like peptide-1 (aGLP-1), peptide tyrosine tyrosine (PYY)-release, and decelerated gastric emptying rates, (ii) a dose-dependent increase in blood glucose and insulin, (iii) no effect on motilin, glucagon, or glucose-dependent insulinotropic peptide (GIP)-release, (iv) no effect on blood lipids, but a rise in uric acid, and (v) increased bowel sounds as only side effects. In conclusion, low doses of xylitol stimulate the secretion of gut hormones and induce a deceleration in gastric emptying rates. There is no effect on blood lipids and only little effect on plasma glucose and insulin. This combination of properties (low-glycemic sweetener which stimulates satiation hormone release) makes xylitol an attractive candidate for sugar replacement.

scholarly journals P-O01 A patient education video to support the management of post-gastrectomy / oesophagectomy syndromes

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Geoffrey Roberts ◽  
Andrew Stone ◽  
Nicola Sunderland ◽  
Sam Grimes ◽  
Frank Reimann ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Patient Education ◽  
Hormone Secretion ◽  
Eating Behaviour ◽  
Physiological Basis ◽  
Upper Gi ◽  
Gut Hormone ◽  
Patient Representatives ◽  
Upper Gi Cancer ◽  
Nutritional Strategies

Abstract Background Oesophagectomy and gastrectomy result in profound and life-long changes in eating behaviour and appetite, and significant post-prandial symptoms. Despite decades of research, and recent advantages in the understanding of gut physiology, medical approaches to post-resectional patient care remain limited. The mainstay of treatment is patient education. Using clinical and lab-based studies, we investigated the effects of altered gut hormone secretion in patients after surgery for oesophageal and gastric cancer. We then produced a partially animated patient information video to better equip our patients to manage their altered alimentation. Methods The scientific background to the video was previously presented at AUGIS, and published. Studies included examination of eating behaviour, post-prandial symptoms, glucose homeostasis, gut hormone profiles and intestinal transcriptomic / peptidomic changes in a cohort of patients after oesophagectomy and gastrectomy. The movie storyboard and script were written by a team of surgeons, dietitians, patient representatives, clinical scientists and communications specialists. The goal was to communicate the physiological basis of altered eating in post-operative patients and appropriate nutritional strategies. Results The video is now freely available on Vimeo at: https://vimeo.com/356892336 It is in routine use for pre- and post-operative patient education. Conclusions Multimedia patient education is a useful tool to help manage the late effects of upper GI cancer treatment.

Proximal and distal gut hormone secretion in slow transit constipation

2000 ◽  
Vol 118 (4) ◽  
pp. A297
Author(s):  
C. Penning ◽  
J.B. Delemarre ◽  
I. Biemond ◽  
C.B. Lamers ◽  
A.A. Masclee
Keyword(s):  
Hormone Secretion ◽  
Slow Transit Constipation ◽  
Gut Hormone ◽  
Slow Transit ◽  
Transit Constipation

scholarly journals A Pilot Study of Gut-Brain Signaling After Octreotide Therapy for Unintentional Weight Loss After Esophagectomy

2020 ◽  
Vol 106 (1) ◽  
pp. e204-e216
Author(s):  
Conor F Murphy ◽  
Nicholas Stratford ◽  
Neil G Docherty ◽  
Brendan Moran ◽  
Jessie A Elliott ◽  
...  
Keyword(s):  
Weight Loss ◽  
Pilot Study ◽  
Food Intake ◽  
Eating Behavior ◽  
Hormone Secretion ◽  
Symptom Burden ◽  
Octreotide Lar ◽  
Gut Hormone ◽  
Ad Libitum ◽  
Brain Reward

Abstract Background Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated postprandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among postesophagectomy patients with unintentional weight loss. Methods This pilot study prospectively studied postoperative patients with 10% or greater body weight loss (BWL) beyond 1 year who were candidates for clinical treatment with long-acting octreotide (LAR). Before and after 4 weeks of treatment, gut hormone secretion, food cue reactivity (functional magnetic resonance imaging), eating motivation (progressive ratio task), ad libitum food intake, body composition, and symptom burden were assessed. Results Eight patients (7 male, age: mean ± SD 62.8 ± 9.4 years, postoperative BWL: 15.5 ± 5.8%) participated. Octreotide LAR did not significantly suppress total postprandial plasma glucagon-like peptide-1 response at 4 weeks (P = .08). Postprandial symptom burden improved after treatment (Sigstad score median [range]: 12 [2-28] vs 8 [3-18], P = .04) but weight remained stable (pre: 68.6 ± 12.8 kg vs post: 69.2 ± 13.4 kg, P = .13). There was no significant change in brain reward system responses, during evaluation of high-energy or low-energy food pictures, nor their appeal rating. Moreover, treatment did not alter motivation to eat (P = .41) nor ad libitum food intake(P = .46). Conclusion The protocol used made it feasible to characterize the gut-brain axis and eating behavior in this cohort. Inadequate suppression of gut hormone responses 4 weeks after octreotide LAR administration may explain the lack of gut-brain pathway alterations. A higher dose or shorter interdose interval may be required to optimize the intervention.

scholarly journals Peripheral Pathways in the Food-Intake Control towards the Adipose-Intestinal Missing Link

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Hugo Mendieta Zerón ◽  
Ma. Victoria Domínguez García ◽  
María del Socorro Camarillo Romero ◽  
Miriam V. Flores-Merino
Keyword(s):  
Diabetes Mellitus ◽  
Genetic Basis ◽  
Physiological State ◽  
Hormone Secretion ◽  
Gut Hormones ◽  
Diabetic Patients ◽  
Early Presentation ◽  
Gut Hormone ◽  
Unknown Factor

In the physiological state a multitude of gut hormones are released into the circulation at the same time depending on the quality and quantity of the diet. These hormones interact with receptors at various points in the “gut-brain axis” to affect short-term and intermediate-term feelings of hunger and satiety. The combined effects of macronutrients on the predominant gut hormone secretion are still poorly understood. Besides, adipokines form an important part of an “adipoinsular axis” dysregulation which may contribute toβ-cell failure and hence to type 2 diabetes mellitus (T2DM). Even more, gestational diabetes mellitus (GDM) and T2DM seem to share a genetic basis. In susceptible individuals, chronic exaggerated stimulation of the proximal gut with fat and carbohydrates may induce overproduction of an unknown factor that causes impairment of incretin production and/or action, leading to insufficient or untimely production of insulin, so that glucose intolerance develops. The bypass of the duodenum and jejunum might avoid a putative hormone overproduction in the proximal foregut in diabetic patients that might counteract the action of insulin, while the early presentation of undigested or incompletely digested food to the ileum may anticipate the production of hormones such as GLP1, further improving insulin action.

scholarly journals Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein–Coupled Bile Acid Receptors

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 3961-3970 ◽  
Author(s):  
Cheryl A. Brighton ◽  
Juraj Rievaj ◽  
Rune E. Kuhre ◽  
Leslie L. Glass ◽  
Kristina Schoonjans ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
G Protein ◽  
Primary Cultures ◽  
Hormone Secretion ◽  
Intracellular Camp ◽  
Ussing Chambers ◽  
L Cells ◽  
Gut Hormone ◽  
G Protein Coupled

Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein–coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1–secreting L-cells from the apical or basolateral compartment. Using transgenic mice expressing fluorescent sensors specifically in L-cells, we observed that taurodeoxycholate (TDCA) and taurolithocholate (TLCA) increased intracellular cAMP and Ca2+. In primary intestinal cultures, TDCA was a more potent GLP-1 secretagogue than taurocholate (TCA) and TLCA, correlating with a stronger Ca2+ response to TDCA. Using small-volume Ussing chambers optimized for measuring GLP-1 secretion, we found that both a GPBAR1 agonist and TDCA stimulated GLP-1 release better when applied from the basolateral than from the luminal direction and that luminal TDCA was ineffective when intestinal tissue was pretreated with an ASBT inhibitor. ASBT inhibition had no significant effect in nonpolarized primary cultures. Studies in the perfused rat gut confirmed that vascularly administered TDCA was more effective than luminal TDCA. Intestinal primary cultures and Ussing chamber–mounted tissues from GPBAR1-knockout mice did not secrete GLP-1 in response to either TLCA or TDCA. We conclude that the action of bile acids on GLP-1 secretion is predominantly mediated by GPBAR1 located on the basolateral L-cell membrane, suggesting that stimulation of gut hormone secretion may include postabsorptive mechanisms.

Taste Receptors in the Gastrointestinal Tract II.l-Amino acid sensing by calcium-sensing receptors: implications for GI physiology

2006 ◽  
Vol 291 (5) ◽  
pp. G753-G761 ◽  
Author(s):  
Arthur D. Conigrave ◽  
Edward M. Brown
Keyword(s):  
Amino Acid ◽  
Gastrointestinal Tract ◽  
Epithelial Transport ◽  
Hormone Secretion ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Gut Hormone ◽  
Protein Ingestion ◽  
Amino Acid Sensing ◽  
Amino Acid Sensor

The extracellular calcium-sensing receptor (CaR) is a multimodal sensor for several key nutrients, notably Ca2+ions and l-amino acids, and is expressed abundantly throughout the gastrointestinal tract. While its role as a Ca2+ion sensor is well recognized, its physiological significance as an l-amino acid sensor and thus, in the gastrointestinal tract, as a sensor of protein ingestion is only now coming to light. This review focuses on the CaR’s amino acid sensing properties at both the molecular and cellular levels and considers new and putative physiological roles for the CaR in the amino acid-dependent regulation of gut hormone secretion, epithelial transport, and satiety.

scholarly journals Cephalic phase secretion of insulin and other enteropancreatic hormones in humans

2016 ◽  
Vol 310 (1) ◽  
pp. G43-G51 ◽  
Author(s):  
Simon Veedfald ◽  
Astrid Plamboeck ◽  
Carolyn F. Deacon ◽  
Bolette Hartmann ◽  
Filip K. Knop ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
Sham Feeding ◽  
C Peptide ◽  
Healthy Men ◽  
Glucose Levels ◽  
Gut Hormone ◽  
Cephalic Phase ◽  
Hormone Responses ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Enteropancreatic hormone secretion is thought to include a cephalic phase, but the evidence in humans is ambiguous. We studied vagally induced gut hormone responses with and without muscarinic blockade in 10 glucose-clamped healthy men (age: 24.5 ± 0.6 yr, means ± SE; body mass index: 24.0 ± 0.5 kg/m2; HbA1c: 5.1 ± 0.1%/31.4 ± 0.5 mmol/mol). Cephalic activation was elicited by modified sham feeding (MSF, aka “chew and spit”) with or without atropine (1 mg bolus 45 min before MSF + 80 ng·kg−1·min−1 for 2 h). To mimic incipient prandial glucose excursions, glucose levels were clamped at 6 mmol/l on all days. The meal stimulus for the MSF consisted of an appetizing breakfast. Participants (9/10) also had a 6 mmol/l glucose clamp without MSF. Pancreatic polypeptide (PP) levels rose from 6.3 ± 1.1 to 19.9 ± 6.8 pmol/l (means ± SE) in response to MSF and atropine lowered basal PP levels and abolished the MSF response. Neither insulin, C-peptide, glucose-dependent insulinotropic polypeptide (GIP), nor glucagon-like peptide-1 (GLP-1) levels changed in response to MSF or atropine. Glucagon and ghrelin levels were markedly attenuated by atropine prior to and during the clamp: at t = 105 min on the atropine (ATR) + clamp (CLA) + MSF compared with the saline (SAL) + CLA and SAL + CLA + MSF days; baseline-subtracted glucagon levels were −10.7 ± 1.1 vs. −4.0 ± 1.1 and −4.7 ± 1.9 pmol/l (means ± SE), P < 0.0001, respectively; corresponding baseline-subtracted ghrelin levels were 303 ± 36 vs. 39 ± 38 and 3.7 ± 21 pg/ml (means ± SE), P < 0.0001. Glucagon and ghrelin levels were unaffected by MSF. Despite adequate PP responses, a cephalic phase response was absent for insulin, glucagon, GLP-1, GIP, and ghrelin.

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