scholarly journals Nutrient-Induced Cellular Mechanisms of Gut Hormone Secretion

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 883
Author(s):  
Van B. Lu ◽  
Fiona M. Gribble ◽  
Frank Reimann
Keyword(s):  
Gastrointestinal Tract ◽  
Hormone Secretion ◽  
Gut Hormones ◽  
Nutrient Sensing ◽  
Enteroendocrine Cells ◽  
Cellular Mechanisms ◽  
Channel Modulation ◽  
Gut Hormone ◽  
Nutrient Utilisation ◽  
Glucagon Like Peptide 1

The gastrointestinal tract can assess the nutrient composition of ingested food. The nutrient-sensing mechanisms in specialised epithelial cells lining the gastrointestinal tract, the enteroendocrine cells, trigger the release of gut hormones that provide important local and central feedback signals to regulate nutrient utilisation and feeding behaviour. The evidence for nutrient-stimulated secretion of two of the most studied gut hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), along with the known cellular mechanisms in enteroendocrine cells recruited by nutrients, will be the focus of this review. The mechanisms involved range from electrogenic transporters, ion channel modulation and nutrient-activated G-protein coupled receptors that converge on the release machinery controlling hormone secretion. Elucidation of these mechanisms will provide much needed insight into postprandial physiology and identify tractable dietary approaches to potentially manage nutrition and satiety by altering the secreted gut hormone profile.

scholarly journals Short-term treatment with olanzapine does not modulate gut hormone secretion: olanzapine disintegrating versus standard tablets

2010 ◽  
Vol 162 (1) ◽  
pp. 75-83 ◽  
Author(s):  
Solrun Vidarsdottir ◽  
Ferdinand Roelfsema ◽  
Trea Streefland ◽  
Jens J Holst ◽  
Jens F Rehfeld ◽  
...  
Keyword(s):  
Weight Gain ◽  
Peptide Yy ◽  
Hormone Secretion ◽  
Gut Hormones ◽  
Term Treatment ◽  
Short Term ◽  
Short Term Treatment ◽  
Healthy Men ◽  
Gut Hormone ◽  
Glucagon Like Peptide 1

BackgroundTreatment with olanzapine (atypical antipsychotic drug) is frequently associated with various metabolic anomalies, including obesity, dyslipidemia, and diabetes mellitus. Recent data suggest that olanzapine orally disintegrating tablets (ODT), which dissolve instantaneously in the mouth, might cause less weight gain than olanzapine standard oral tablets (OST).Design and methodsTen healthy men received olanzapine ODT (10 mg o.d., 8 days), olanzapine OST (10 mg o.d., 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, blood samples were taken for measurement of pancreatic polypeptide, peptide YY, glucagon-like peptide-1, total glucagon, total ghrelin, and cholecystokinin (CCK) concentrations.ResultsWith the exception of pre- and postprandial concentration of ghrelin at dinner and preprandial CCK concentrations at breakfast, which were all slightly increased (respectivelyP=0.048,P=0.034 andP=0.042), olanzapine did not affect gut hormone concentrations. Thus, olanzapine ODT and OST had similar effects on gut hormone secretion.ConclusionShort-term treatment with olanzapine does not have major impact on the plasma concentration of gut hormones we measured in healthy men. Moreover, despite pharmacological difference, gut hormone concentrations are similar during treatment with olanzapine ODT and OST. The capacity of olanzapine to induce weight gain and diabetes is unlikely to be caused by modulation of the secretion of gut hormones measured here. We cannot exclude the possibility that olanzapine's impact on other gut hormones, to impair insulin sensitivity and stimulate weight gain, exists.

scholarly journals Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans

2014 ◽  
Vol 306 (7) ◽  
pp. G622-G630 ◽  
Author(s):  
Rune E. Kuhre ◽  
Fiona M. Gribble ◽  
Bolette Hartmann ◽  
Frank Reimann ◽  
Johanne A. Windeløv ◽  
...  
Keyword(s):  
Peptide Yy ◽  
Hormone Secretion ◽  
Gut Hormones ◽  
Glucagon Secretion ◽  
Healthy Humans ◽  
Murine Cell Line ◽  
Gut Hormone ◽  
Glucagon Like Peptide 1 ◽  
Cell Depolarization ◽  
Gip Release

Nutrients often stimulate gut hormone secretion, but the effects of fructose are incompletely understood. We studied the effects of fructose on a number of gut hormones with particular focus on glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). In healthy humans, fructose intake caused a rise in blood glucose and plasma insulin and GLP-1, albeit to a lower degree than isocaloric glucose. Cholecystokinin secretion was stimulated similarly by both carbohydrates, but neither peptide YY3–36nor glucagon secretion was affected by either treatment. Remarkably, while glucose potently stimulated GIP release, fructose was without effect. Similar patterns were found in the mouse and rat, with both fructose and glucose stimulating GLP-1 secretion, whereas only glucose caused GIP secretion. In GLUTag cells, a murine cell line used as model for L cells, fructose was metabolized and stimulated GLP-1 secretion dose-dependently (EC50= 0.155 mM) by ATP-sensitive potassium channel closure and cell depolarization. Because fructose elicits GLP-1 secretion without simultaneous release of glucagonotropic GIP, the pathways underlying fructose-stimulated GLP-1 release might be useful targets for type 2 diabetes mellitus and obesity drug development.

scholarly journals Targeting the Gut in Obesity: Signals from the Inner Surface

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 39
Author(s):  
Natalia Petersen ◽  
Thomas U. Greiner ◽  
Lola Torz ◽  
Angie Bookout ◽  
Marina Kjærgaard Gerstenberg ◽  
...  
Keyword(s):  
Direct Interaction ◽  
Gut Hormones ◽  
Energy Balance Equation ◽  
Enteroendocrine Cells ◽  
Therapeutic Interventions ◽  
Microbial Metabolites ◽  
Dipeptidyl Peptidase 4 ◽  
Gut Hormone ◽  
Glucagon Like Peptide 1 ◽  
The Brain

Obesity is caused by prolonged energy surplus. Current anti-obesity medications are mostly centralized around the energy input part of the energy balance equation by increasing satiety and reducing appetite. Our gastrointestinal tract is a key organ for regulation of food intake and supplies a tremendous number of circulating signals that modulate the activity of appetite-regulating areas of the brain by either direct interaction or through the vagus nerve. Intestinally derived messengers are manifold and include absorbed nutrients, microbial metabolites, gut hormones and other enterokines, collectively comprising a fine-tuned signalling system to the brain. After a meal, nutrients directly interact with appetite-inhibiting areas of the brain and induce satiety. However, overall feeding behaviour also depends on secretion of gut hormones produced by highly specialized and sensitive enteroendocrine cells. Moreover, circulating microbial metabolites and their interactions with enteroendocrine cells further contribute to the regulation of feeding patterns. Current therapies exploiting the appetite-regulating properties of the gut are based on chemically modified versions of the gut hormone, glucagon-like peptide-1 (GLP-1) or on inhibitors of the primary GLP-1 inactivating enzyme, dipeptidyl peptidase-4 (DPP-4). The effectiveness of these approaches shows that that the gut is a promising target for therapeutic interventions to achieve significant weigh loss. We believe that increasing understanding of the functionality of the intestinal epithelium and new delivery systems will help develop selective and safe gut-based therapeutic strategies for improved obesity treatment in the future. Here, we provide an overview of the major homeostatic appetite-regulating signals generated by the intestinal epithelial cells and how these signals may be harnessed to treat obesity by pharmacological means.

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 Neurotensin Is Coexpressed, Coreleased, and Acts Together With GLP-1 and PYY in Enteroendocrine Control of Metabolism

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 176-194 ◽  
Author(s):  
Kaare V. Grunddal ◽  
Cecilia F. Ratner ◽  
Berit Svendsen ◽  
Felix Sommer ◽  
Maja S. Engelstoft ◽  
...  
Keyword(s):  
Peptide Yy ◽  
Secretory Granules ◽  
Gut Hormones ◽  
Distal Small Intestine ◽  
Cell Ablation ◽  
Target Organs ◽  
Gut Hormone ◽  
Toxin Receptor ◽  
Functional Consequences ◽  
Glucagon Like Peptide 1

Abstract The 2 gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are well known to be coexpressed, costored, and released together to coact in the control of key metabolic target organs. However, recently, it became clear that several other gut hormones can be coexpressed in the intestinal-specific lineage of enteroendocrine cells. Here, we focus on the anatomical and functional consequences of the coexpression of neurotensin with GLP-1 and PYY in the distal small intestine. Fluorescence-activated cell sorting analysis, laser capture, and triple staining demonstrated that GLP-1 cells in the crypts become increasingly multihormonal, ie, coexpressing PYY and neurotensin as they move up the villus. Proglucagon promoter and pertussis toxin receptor-driven cell ablation and reappearance studies indicated that although all the cells die, the GLP-1 cells reappear more quickly than PYY- and neurotensin-positive cells. High-resolution confocal fluorescence microscopy demonstrated that neurotensin is stored in secretory granules distinct from GLP-1 and PYY storing granules. Nevertheless, the 3 peptides were cosecreted from both perfused small intestines and colonic crypt cultures in response to a series of metabolite, neuropeptide, and hormonal stimuli. Importantly, neurotensin acts synergistically, ie, more than additively together with GLP-1 and PYY to decrease palatable food intake and inhibit gastric emptying, but affects glucose homeostasis in a more complex manner. Thus, neurotensin is a major gut hormone deeply integrated with GLP-1 and PYY, which should be taken into account when exploiting the enteroendocrine regulation of metabolism pharmacologically.

DIFFERENTIAL EFFECTS OF BILE ACIDS ON THE POST-PRANDIAL SECRETION OF GUT HORMONES: a randomised crossover study

2021 ◽  
Author(s):  
Emma Rose McGlone ◽  
Khalefah Malallah ◽  
Joyceline Cuenco ◽  
Nicolai J. Wewer Albrechtsen ◽  
Jens J. Holst ◽  
...  
Keyword(s):  
Bile Acids ◽  
Peptide Yy ◽  
Gut Hormones ◽  
Mixed Meal ◽  
Gut Hormone ◽  
Mixed Meal Test ◽  
Hormone Responses ◽  
Glucagon Like Peptide 1 ◽  
Fibroblast Growth Factor 19 ◽  
Insulinotropic Peptide

AIMS Bile acids (BA) regulate post-prandial metabolism directly and indirectly by affecting the secretion of gut hormones like glucagon-like peptide-1 (GLP-1). The post-prandial effects of BA on the secretion of other metabolically active hormones are not well understood. The objective of this study was to investigate the effect of oral ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on post-prandial secretion of GLP-1, oxyntomodulin (OXM), peptide YY (PYY), glucose-dependent insulinotropic peptide (GIP), glucagon and ghrelin. METHODS Twelve healthy volunteers underwent a mixed meal test 60 minutes after ingestion of UDCA (12-16 mg/kg), CDCA (13-16 mg/kg) or no BA in a randomised cross-over study. Glucose, insulin, GLP-1, OXM, PYY, GIP, glucagon, ghrelin and fibroblast growth factor 19 were measured prior to BA administration at -60, 0 (just prior to mixed meal) and 15, 30, 60, 120, 180 and 240 minutes after the meal. RESULTS UDCA and CDCA provoked differential gut hormone responses: UDCA did not have any significant effects, but CDCA provoked significant increases in GLP-1 and OXM and a profound reduction in GIP. CDCA increased fasting GLP-1 and OXM secretion in parallel with an increase in insulin. On the other hand, CDCA reduced post-prandial secretion of GIP, with an associated reduction in post-prandial insulin secretion. CONCLUSIONS Exogenous CDCA can exert multiple salutary effects on the secretion of gut hormones; if these effects are confirmedin obesity and type 2 diabetes, CDCA may be a potential therapy for these conditions.

scholarly journals MON-589 Studying Mechanisms of Satiety in the Human Ileum and Colon

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Anya Ramgulam ◽  
Martina Tashkova ◽  
Maeve O’Driscoll ◽  
Georgia Franco Becker ◽  
Hannah Stephens ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Glucose Homeostasis ◽  
Peptide Yy ◽  
Gut Hormones ◽  
16S Rrna Gene Sequencing ◽  
Gut Contents ◽  
Rrna Gene ◽  
Clinical Research Facility ◽  
Glucagon Like Peptide 1 ◽  
Rrna Gene Sequencing

Abstract Background The gut-brain axis plays important roles in the regulation of appetite and glucose homeostasis. The presence of nutrients and their digestive products in specific regions of the gastrointestinal tract modulates neuronal and hormonal signalling, including the release of the appetite-suppressing gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). While there has been significant research into the upper gut mechanisms behind satiation, i.e. the termination of meal, the role of the ileum and colon in satiety, i.e. the process which delays a subsequent meal, has been relatively little investigated, particularly in humans. Methods Ten healthy volunteers attended our Clinical Research Facility for two visits of four days each. At each visit they had either a nasoileal or a nasocolonic tube inserted under fluoroscopy. They were then provided a diet rich in protein and fibre to promote satiety. Gut contents and blood samples were taken before and during test meals at the start and end of the visit, and visual analogue scales were used to measure subjective feelings of appetite. Metabonomic analysis of gut fluid was carried out using a combination of in-house NMR and LC-MS-based methods. 16S rRNA gene sequencing was used to investigate effects on the colonic microbiome. Circulating levels of glucose, the gut hormones GLP-1 and PYY, and the pancreatic hormones insulin and glucagon were measured. Results and discussion The test meals resulted in sustained suppression of appetite and release of GLP-1 and PYY. Ileal and colonic microbial profiles were distinct from those identified in stool samples, and changed with adaptation to the high protein and fibre diet. Integrating hormonal, metabonomic and bacterial datasets from these human studies gives insight into how nutrient and metabolite sensing in the gastrointestinal tract regulates appetite and glucose homeostasis, and may suggest novel therapeutic targets for metabolic disease.

scholarly journals Plant-rich mixed meals based on Palaeolithic diet principles have a dramatic impact on incretin, peptide YY and satiety response, but show little effect on glucose and insulin homeostasis: an acute-effects randomised study

2015 ◽  
Vol 113 (4) ◽  
pp. 574-584 ◽  
Author(s):  
H. Frances J. Bligh ◽  
Ian F. Godsland ◽  
Gary Frost ◽  
Karl J. Hunter ◽  
Peter Murray ◽  
...  
Keyword(s):  
Peptide Yy ◽  
Blood Glucose Control ◽  
Gut Hormones ◽  
Acute Effects ◽  
Randomised Study ◽  
Satiety Response ◽  
Gut Hormone ◽  
Palaeolithic Diet ◽  
Glucagon Like Peptide 1 ◽  
Few Data

There is evidence for health benefits from ‘Palaeolithic’ diets; however, there are a few data on the acute effects of rationally designed Palaeolithic-type meals. In the present study, we used Palaeolithic diet principles to construct meals comprising readily available ingredients: fish and a variety of plants, selected to be rich in fibre and phyto-nutrients. We investigated the acute effects of two Palaeolithic-type meals (PAL 1 and PAL 2) and a reference meal based on WHO guidelines (REF), on blood glucose control, gut hormone responses and appetite regulation. Using a randomised cross-over trial design, healthy subjects were given three meals on separate occasions. PAL2 and REF were matched for energy, protein, fat and carbohydrates; PAL1 contained more protein and energy. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) concentrations were measured over a period of 180 min. Satiation was assessed using electronic visual analogue scale (EVAS) scores. GLP-1 and PYY concentrations were significantly increased across 180 min for both PAL1 (P= 0·001 and P< 0·001) and PAL2 (P= 0·011 and P= 0·003) compared with the REF. Concomitant EVAS scores showed increased satiety. By contrast, GIP concentration was significantly suppressed. Positive incremental AUC over 120 min for glucose and insulin did not differ between the meals. Consumption of meals based on Palaeolithic diet principles resulted in significant increases in incretin and anorectic gut hormones and increased perceived satiety. Surprisingly, this was independent of the energy or protein content of the meal and therefore suggests potential benefits for reduced risk of obesity.

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.

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.

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