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1.
Mechanisms controlling hormone secretion in human gut and its relevance to metabolism.
Martin, AM, Sun, EW, Keating, DJ
The Journal of endocrinology. 2019;(1):R1-R15
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Abstract
The homoeostatic regulation of metabolism is highly complex and involves multiple inputs from both the nervous and endocrine systems. The gut is the largest endocrine organ in our body and synthesises and secretes over 20 different hormones from enteroendocrine cells that are dispersed throughout the gut epithelium. These hormones include GLP-1, PYY, GIP, serotonin, and CCK, each of whom play pivotal roles in maintaining energy balance and glucose homeostasis. Some are now the basis of several clinically used glucose-lowering and weight loss therapies. The environment in which these enteroendocrine cells exist is also complex, as they are exposed to numerous physiological inputs including ingested nutrients, circulating factors and metabolites produced from neighbouring gut microbiome. In this review, we examine the diverse means by which gut-derived hormones carry out their metabolic functions through their interactions with different metabolically important organs including the liver, pancreas, adipose tissue and brain. Furthermore, we discuss how nutrients and microbial metabolites affect gut hormone secretion and the mechanisms underlying these interactions.
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Diet in Irritable Bowel Syndrome (IBS): Interaction with Gut Microbiota and Gut Hormones.
El-Salhy, M, Hatlebakk, JG, Hausken, T
Nutrients. 2019;(8)
Abstract
Diet plays an important role not only in the pathophysiology of irritable bowel syndrome (IBS), but also as a tool that improves symptoms and quality of life. The effects of diet seem to be a result of an interaction with the gut bacteria and the gut endocrine cells. The density of gut endocrine cells is low in IBS patients, and it is believed that this abnormality is the direct cause of the symptoms seen in IBS patients. The low density of gut endocrine cells is probably caused by a low number of stem cells and low differentiation progeny toward endocrine cells. A low fermentable oligo-, di-, monosaccharide, and polyol (FODMAP) diet and fecal microbiota transplantation (FMT) restore the gut endocrine cells to the level of healthy subjects. It has been suggested that our diet acts as a prebiotic that favors the growth of a certain types of bacteria. Diet also acts as a substrate for gut bacteria fermentation, which results in several by-products. These by-products might act on the stem cells in such a way that the gut stem cells decrease, and consequently, endocrine cell numbers decrease. Changing to a low-FODMAP diet or changing the gut bacteria through FMT improves IBS symptoms and restores the density of endocrine cells.
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Effects of chewing on appetite, food intake and gut hormones: A systematic review and meta-analysis.
Miquel-Kergoat, S, Azais-Braesco, V, Burton-Freeman, B, Hetherington, MM
Physiology & behavior. 2015;:88-96
Abstract
OBJECTIVES To seek insights into the relationship between chewing, appetite, food intake and gut hormones, and to consider potentially useful recommendations to promote benefits of chewing for weight management. MATERIALS AND METHODS Papers were obtained from two electronic databases (Medline and Cochrane), from searches of reference lists, and from raw data collected from the figures in the articles. A total of 15 papers were identified that detailed 17 trials. All 15 papers were included in the systematic review; however, a further five studies were excluded from the meta-analysis because appropriate information on hunger ratings was not available. The meta-analysis was conducted on a total of 10 papers that detailed 13 trials. RESULTS Five of 16 experiments found a significant effect of chewing on satiation or satiety using self-report measures (visual analogue scales, VASs). Ten of 16 experiments found that chewing reduced food intake. Three of five studies showed that increasing the number of chews per bite increased relevant gut hormones and two linked this to subjective satiety. The meta-analysis found evidence of both publication bias and between study heterogeneity (IA(2) = 93.4%, tau(2) = 6.52, p < 0.001) which decreased, but remained, when covariates were considered. Analysis of the heterogeneity found a substantial effect of the fasting period where the duration of fasting influenced the decrease in hunger due to chewing. Prolonged mastication significantly reduces self-reported hunger levels (hunger: − 2.31 VAS point, 95% CI [− 4.67, − 1.38], p < 0.001). CONCLUSIONS Evidence currently suggests that chewing may decrease self-reported hunger and food intake, possibly through alterations in gut hormone responses related to satiety. Although preliminary, the results identify a need for additional research in the area. Focused, uniform, experimental designs are required to clearly understand the relationships that exist between mastication, appetite, satiety, food intake and, ultimately, body weight.
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Hormonal signaling in the gut.
Côté, CD, Zadeh-Tahmasebi, M, Rasmussen, BA, Duca, FA, Lam, TKT
The Journal of biological chemistry. 2014;(17):11642-11649
Abstract
The gut is anatomically positioned to play a critical role in the regulation of metabolic homeostasis, providing negative feedback via nutrient sensing and local hormonal signaling. Gut hormones, such as cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1), are released following a meal and act on local receptors to regulate glycemia via a neuronal gut-brain axis. Additionally, jejunal nutrient sensing and leptin action are demonstrated to suppress glucose production, and both are required for the rapid antidiabetic effect of duodenal jejunal bypass surgery. Strategies aimed at targeting local gut hormonal signaling pathways may prove to be efficacious therapeutic options to improve glucose control in diabetes.
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Gastrointestinal changes after bariatric surgery.
Quercia, I, Dutia, R, Kotler, DP, Belsley, S, Laferrère, B
Diabetes & metabolism. 2014;(2):87-94
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Abstract
Severe obesity is a preeminent health care problem that impacts overall health and survival. The most effective treatment for severe obesity is bariatric surgery, an intervention that not only maintains long-term weight loss but also is associated with improvement or remission of several comorbidies including type 2 diabetes mellitus. Some weight loss surgeries modify the gastrointestinal anatomy and physiology, including the secretions and actions of gut peptides. This review describes how bariatric surgery alters the patterns of gastrointestinal motility, nutrient digestion and absorption, gut peptide release, bile acids and the gut microflora, and how these changes alter energy homeostasis and glucose metabolism.
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Metabolic surgery: action via hormonal milieu changes, changes in bile acids or gut microbiota? A summary of the literature.
Sweeney, TE, Morton, JM
Best practice & research. Clinical gastroenterology. 2014;(4):727-40
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Abstract
Obesity and type 2 diabetes remain epidemic problems. Different bariatric surgical techniques causes weight loss and diabetes remission to varying degrees. The underlying mechanisms of the beneficial effects of bariatric surgery are complex, and include changes in diet and behaviour, as well as changes in hormones, bile acid flow, and gut bacteria. We summarized the effects of multiple different bariatric procedures, and their resulting effects on several hormones (leptin, ghrelin, adiponectin, glucagon-like peptide 1 (GLP-1), peptide YY, and glucagon), bile acid changes in the gut and the serum, and resulting changes to the gut microbiome. As much as possible, we have tried to incorporate multiple studies to try to explain underlying mechanistic changes. What emerges from the data is a picture of clear differences between restrictive and metabolic procedures. The latter, in particular the roux-en-Y gastric bypass, induces large and distinctive changes in most measured fat and gut hormones, including early and sustained increase in GLP-1, possible through intestinal bile acid signalling. The changes in bile flow and the gut microbiome are causally inseparable so far, but new studies show that each contributes to the effects of weight loss and diabetes resolution.
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Review article: the role of gastrointestinal hormones in the treatment of delayed gastric emptying in critically ill patients.
Luttikhold, J, de Ruijter, FM, van Norren, K, Diamant, M, Witkamp, RF, van Leeuwen, PA, Vermeulen, MA
Alimentary pharmacology & therapeutics. 2013;(6):573-83
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Abstract
BACKGROUND Delayed gastric emptying limits the administration of enteral nutrition, leading to malnutrition, which is associated with higher mortality and morbidity. Currently available prokinetics have limitations in terms of sustained efficacy and side effects. AIM: To summarise the mechanisms of action and to discuss the possible utility of gastrointestinal hormones to prevent or treat delayed gastric emptying in critically ill patients. METHODS We searched PubMed for articles discussing 'delayed gastric emptying', 'enteral nutrition', 'treatment', 'gastrointestinal hormones', 'prokinetic', 'agonist', 'antagonist' and 'critically ill patients'. RESULTS Motilin and ghrelin receptor agonists initiate the migrating motor complex in the stomach, which accelerates gastric emptying. Cholecystokinin, glucagon-like peptide-1 and peptide YY have an inhibiting effect on gastric emptying; therefore, antagonising these gastrointestinal hormones may have therapeutic potential. Other gastrointestinal hormones appear less promising. CONCLUSIONS Manipulation of endogenous secretion, physiological replacement and administration of gastrointestinal hormones in pharmacological doses is likely to have therapeutic potential in the treatment of delayed gastric emptying. Future challenges in this field will include the search for candidates with improved selectivity and favourable kinetic properties.
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Pendrin, a novel transcriptional target of the uroguanylin system.
Rozenfeld, J, Tal, O, Kladnitsky, O, Adler, L, Efrati, E, Carrithers, SL, Alper, SL, Zelikovic, I
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2013;(7):221-37
Abstract
Guanylin (GN) and uroguanylin (UGN) are low-molecular-weight peptide hormones produced mainly in the intestinal mucosa in response to oral salt load. GN and UGN (guanylin peptides) induce secretion of electrolytes and water in both intestine and kidney. Thought to act as "intestinal natriuretic factors", GN and UGN modulate renal salt secretion by both endocrine mechanisms (linking the digestive system and kidney) and paracrine/autocrine (intrarenal) mechanisms. The cellular function of GN and UGN in intestine and proximal tubule is mediated by guanylyl cyclase C (GC-C)-, cGMP-, and G protein-dependent pathways, whereas, in principal cells of the cortical collecting duct (CCD), these peptide hormones act via GC-C-independent signaling through phospholipase A2 (PLA2). The Cl(-)/HCO(-)3 exchanger pendrin (SLC26A4), encoded by the PDS gene, is expressed in non-α intercalated cells of the CCD. Pendrin is essential for CCD bicarbonate secretion and is also involved in NaCl balance and blood pressure regulation. Our recent studies have provided evidence that pendrin-mediated anion exchange in the CCD is regulated at the transcriptional level by UGN. UGN exerts an inhibitory effect on the pendrin gene promoter likely via heat shock factor 1 (HSF1) action at a defined heat shock element (HSE) site. Recent studies have unraveled novel roles for guanylin peptides in several organ systems including involvement in appetite regulation, olfactory function, cell proliferation and differentiation, inflammation, and reproductive function. Both the guanylin system and pendrin have also been implicated in airway function. Future molecular research into the receptors and signal transduction pathways involved in the action of guanylin peptides and the pendrin anion exchanger in the kidney and other organs, and into the links between them, may facilitate discovery of new therapies for hypertension, heart failure, hepatic failure and other fluid retention syndromes, as well as for diverse diseases such as obesity, asthma, and cancer.
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Gastrointestinal hormones and bariatric surgery-induced weight loss.
Ionut, V, Burch, M, Youdim, A, Bergman, RN
Obesity (Silver Spring, Md.). 2013;(6):1093-103
Abstract
UNLABELLED Obesity continues to be a major public health problem in the United States and worldwide. While recent statistics have demonstrated that obesity rates have begun to plateau, more severe classes of obesity are accelerating at a faster pace with important implications in regards to treatment. Bariatric surgery has a profound and durable effect on weight loss, being to date one of the most successful interventions for obesity. OBJECTIVE To provide updates to the possible role of gut hormones in post bariatric surgery weight loss and weight loss maintenance. DESIGN AND METHODS The current review examines the changes in gastro-intestinal hormones with bariatric surgery and the potential mechanisms by which these changes could result in decreased weight and adiposity. RESULTS The mechanism by which bariatric surgery results in body weight changes is incompletely elucidated, but it clearly goes beyond caloric restriction and malabsorption. CONCLUSION Changes in gastro-intestinal hormones, including increases in GLP-1, PYY, and oxyntomodulin, decreases in GIP and ghrelin, or the combined action of all these hormones might play a role in induction and long-term maintenance of weight loss.
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10.
Gut feelings about diabetes.
Laferrère, B
Endocrinologia y nutricion : organo de la Sociedad Espanola de Endocrinologia y Nutricion. 2012;(4):254-60
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Abstract
Studies of patients going into diabetes remission after gastric bypass surgery have demonstrated the important role of the gut in glucose control. The improvement of type 2 diabetes after gastric bypass surgery occurs via weight dependent and weight independent mechanisms. The rapid improvement of glucose levels within days after the surgery, in relation to change of meal pattern, rapid nutrient transit, enhanced incretin release and improved incretin effect on insulin secretion, suggest mechanisms independent of weight loss. Alternatively, insulin sensitivity improves over time as a function of weight loss. The role of bile acids and microbiome in the metabolic improvement after bariatric surgery remains to be determined. While most patients after bariatric surgery experienced sustained weight loss and improved metabolism, small scale studies have shown weight regain and diabetes relapse, the mechanisms of which remain unknown.