The Role of Gasotransmitters in Gut Peptide Actions

Although gasotransmitters nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) receive a bad connotation; in low concentrations these play a major governing role in local and systemic blood flow, stomach acid release, smooth muscles relaxations, anti-inflammatory behavior, protective effect and more. Many of these physiological processes are upstream regulated by gut peptides, for instance gastrin, cholecystokinin, secretin, motilin, ghrelin, glucagon-like peptide 1 and 2. The relationship between gasotransmitters and gut hormones is poorly understood. In this review, we discuss the role of NO, CO and H2S on gut peptide release and functioning, and whether manipulation by gasotransmitter substrates or specific blockers leads to physiological alterations.

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The Emerging Role of Polyphenols in the Management of Type 2 Diabetes

Molecules ◽

10.3390/molecules26030703 ◽

2021 ◽

Vol 26 (3) ◽

pp. 703

Author(s):

Yao Wang ◽

Hana Alkhalidy ◽

Dongmin Liu

Keyword(s):

Type 2 Diabetes ◽

Glucose Homeostasis ◽

Gut Hormones ◽

Nutritional Regulation ◽

Gi Tract ◽

Cell Dysfunction ◽

Glucagon Like Peptide 1 ◽

Metabolic Action

Type 2 diabetes (T2D) is a fast-increasing health problem globally, and it results from insulin resistance and pancreatic β-cell dysfunction. The gastrointestinal (GI) tract is recognized as one of the major regulatory organs of glucose homeostasis that involves multiple gut hormones and microbiota. Notably, the incretin hormone glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L-cells plays a pivotal role in maintaining glucose homeostasis via eliciting pleiotropic effects, which are largely mediated via its receptor. Thus, targeting the GLP-1 signaling system is a highly attractive therapeutic strategy to treatment T2D. Polyphenols, the secondary metabolites from plants, have drawn considerable attention because of their numerous health benefits, including potential anti-diabetic effects. Although the major targets and locations for the polyphenolic compounds to exert the anti-diabetic action are still unclear, the first organ that is exposed to these compounds is the GI tract in which polyphenols could modulate enzymes and hormones. Indeed, emerging evidence has shown that polyphenols can stimulate GLP-1 secretion, indicating that these natural compounds might exert metabolic action at least partially mediated by GLP-1. This review provides an overview of nutritional regulation of GLP-1 secretion and summarizes recent studies on the roles of polyphenols in GLP-1 secretion and degradation as it relates to metabolic homeostasis. In addition, the effects of polyphenols on microbiota and microbial metabolites that could indirectly modulate GLP-1 secretion are also discussed.

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Loss of cholecystokinin and glucagon-like peptide-1-induced satiation in mice lacking serotonin 2C receptors

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.90655.2008 ◽

2009 ◽

Vol 296 (1) ◽

pp. R51-R56 ◽

Cited By ~ 26

Author(s):

Lori Asarian

Keyword(s):

Neural Mechanisms ◽

Wild Type ◽

Gut Peptides ◽

Serotonin Signaling ◽

The Central Nervous System ◽

Fos Expression ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

The Brain

To investigate the role of serotonin 2C receptors (2CR), which are expressed only in the central nervous system, in the satiating actions of the gut peptides CCK and glucagon-like peptide 1 (GLP-1), we examined 1) the effect of null mutations of serotonin 2CR (2CR KO) on the eating-inhibitory potencies of dark-onset intraperitoneal injections of 0.9, 1.7, or 3.5 nmol/kg (1, 2, or 4 μg/kg) CCK and 100, 200, and 400 nmol/kg (33, 66, or 132 μg/kg) GLP-1, and 2) the effects of intraperitoneal injections of 1.7 nmol//kg CCK and 100 nmol/kg GLP-1 on neuronal activation in the brain, as measured by c-Fos expression. All CCK and GLP-1 doses decreased 30-min food intake in wild-type (WT) mice, but none of them did in 2CR KO mice. CCK increased the number of cells expressing c-Fos in the nucleus tractus solitarii (NTS) of WT, but not 2CR KO mice. CCK induced similar degrees of c-Fos expression in the paraventricular (PVN) and arcuate (Arc) nuclei of the hypothalamus of both genotypes. GLP-1, on the other hand, increased c-Fos expression similarly in the NTS of both genotypes and increased c-Fos expression more in the PVN and Arc of 2CR KO mice, but not WT mice. These results indicate that serotonin signaling via serotonin 2CR is necessary for the full satiating effects of CCK and GLP-1. In addition, they suggest that the satiating effects of the two peptides are mediated by different neural mechanisms.

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Current and emerging concepts on the role of peripheral signals in the control of food intake and development of obesity

British Journal Of Nutrition ◽

10.1017/s0007114512000529 ◽

2012 ◽

Vol 108 (5) ◽

pp. 778-793 ◽

Cited By ~ 29

Author(s):

F. A. Duca ◽

M. Covasa

Keyword(s):

Body Weight ◽

Energy Homeostasis ◽

Peptide Yy ◽

Body Weight Gain ◽

Gut Peptides ◽

Gastrointestinal Peptides ◽

Term Energy ◽

Glucagon Like Peptide 1 ◽

Treatment Of Obesity

The gastrointestinal peptides are classically known as short-term signals, primarily inducing satiation and/or satiety. However, accumulating evidence has broadened this view, and their role in long-term energy homeostasis and the development of obesity has been increasingly recognised. In the present review, the recent research involving the role of satiation signals, especially ghrelin, cholecystokinin, glucagon-like peptide 1 and peptide YY, in the development and treatment of obesity will be discussed. Their activity, interactions and release profile vary constantly with changes in dietary and energy influences, intestinal luminal environment, body weight and metabolic status. Manipulation of gut peptides and nutrient sensors in the oral and postoral compartments through diet and/or changes in gut microflora or using multi-hormone ‘cocktail’ therapy are among promising approaches aimed at reducing excess food consumption and body-weight gain.

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Gastrointestinal peptides and small-bowel hypomotility are possible causes for fasting and postprandial symptoms in active Crohn's disease

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz240 ◽

2019 ◽

Vol 111 (1) ◽

pp. 131-140

Author(s):

Asseel Khalaf ◽

Caroline L Hoad ◽

Alex Menys ◽

Adam Nowak ◽

Shellie Radford ◽

...

Keyword(s):

Crohn’S Disease ◽

Small Bowel ◽

Crohn's Disease ◽

Gut Hormones ◽

Standard Test ◽

Gut Peptides ◽

Bowel Motility ◽

Small Bowel Motility ◽

Mri Scans ◽

Glucagon Like Peptide 1

ABSTRACT Background Crohn's disease (CD) patients suffer postprandial aversive symptoms, which can lead to anorexia and malnutrition. Changes in the regulation of gut hormones and gut dysmotility are believed to play a role. Objectives This study aimed to investigate small-bowel motility and gut peptide responses to a standard test meal in CD by using MRI. Methods We studied 15 CD patients with active disease (age 36 ± 3 y; BMI 26 ± 1 kg/m 2) and 20 healthy volunteers (HVs; age 31 ± 3 years; BMI 24 ± 1 kg/m 2). They underwent baseline and postprandial MRI scans, symptom questionnaires, and blood sampling following a 400-g soup meal (204 kcal). Small-bowel motility, other MRI parameters, and glucagon-like peptide-1 (GLP-1), polypeptide YY (PYY), and cholecystokinin peptides were measured. Data are presented as means ± SEMs. Results HVs had significantly higher fasting motility indexes [106 ± 13 arbitrary units (a.u.)], compared with CD participants (70 ± 8 a.u.; P ≤ 0.05). Postprandial small-bowel water content showed a significant time by group interaction (P < 0.05), with CD participants showing higher levels from 210 min postprandially. Fasting concentrations of GLP-1 and PYY were significantly greater in CD participants, compared with HVs [GLP-1, CD 50 ± 8 µg/mL versus HV 13 ± 3 µg/mL (P ≤ 0.0001); PYY, CD 236 ± 16 pg/mL versus HV 118 ± 12 pg/mL (P ≤ 0.0001)]. The meal challenge induced a significant postprandial increase in aversive symptom scores (fullness, distention, bloating, abdominal pain, and sickness) in CD participants compared with HVs (P ≤ 0.05). Conclusions The decrease in fasting small-bowel motility noted in CD participants can be ascribed to the increased fasting gut peptides. A better understanding of the etiology of aversive symptoms in CD will facilitate identification of better therapeutic targets to improve nutritional status. This trial was registered at clinicaltrials.gov as NCT03052465.

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The Role of the Bacterial Muramyl Dipeptide in the Regulation of GLP-1 and Glycemia

International Journal of Molecular Sciences ◽

10.3390/ijms21155252 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5252

Author(s):

Laura Williams ◽

Amal Alshehri ◽

Bianca Robichaud ◽

Alison Cudmore ◽

Jeffrey Gagnon

Keyword(s):

Glucose Tolerance ◽

Muramyl Dipeptide ◽

Gut Hormones ◽

Oral Glucose ◽

L Cells ◽

Nucleotide Oligomerization ◽

Mouse Intestine ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

The host’s intestinal microbiota contributes to endocrine and metabolic responses, but a dysbiosis in this environment can lead to obesity and insulin resistance. Recent work has demonstrated a role for microbial metabolites in the regulation of gut hormones, including the metabolic hormone, glucagon-like peptide-1 (GLP-1). Muramyl dipeptide (MDP) is a bacterial cell wall component which has been shown to improve insulin sensitivity and glucose tolerance in diet-induced obese mice by acting through the nucleotide oligomerization domain 2 (NOD2) receptor. The purpose of this study was to understand the effects of MDP on GLP-1 secretion and glucose regulation. We hypothesized that MDP enhances glucose tolerance by inducing intestinal GLP-1 secretion through NOD2 activation. First, we observed a significant increase in GLP-1 secretion when murine and human L-cells were treated with a fatty acid MDP derivative (L18-MDP). Importantly, we demonstrated the expression of the NOD2 receptor in mouse intestine and in L-cells. In mice, two intraperitoneal injections of MDP (5 mg/kg body weight) caused a significant increase in fasting total GLP-1 in chow-fed mice, however this did not lead to an improvement in oral glucose tolerance. When mice were exposed to a high-fat diet, they eventually lost this MDP-induced GLP-1 release. Finally, we demonstrated in L-cells that hyperglycemic conditions reduce the mRNA expression of NOD2 and GLP-1. Together these findings suggest MDP may play a role in enhancing GLP-1 during normal glycemic conditions but loses its ability to do so in hyperglycemia.

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Role of Gut Microbiota in Neuroendocrine Regulation of Carbohydrate and Lipid Metabolism via the Microbiota-Gut-Brain-Liver Axis

Microorganisms ◽

10.3390/microorganisms8040527 ◽

2020 ◽

Vol 8 (4) ◽

pp. 527 ◽

Cited By ~ 6

Author(s):

Shu-Zhi Wang ◽

Yi-Jing Yu ◽

Khosrow Adeli

Keyword(s):

Nervous System ◽

Gut Microbiota ◽

Immunoglobulin A ◽

Short Chain Fatty Acids ◽

Neuroendocrine Regulation ◽

Gut Peptides ◽

Nutrient Metabolism ◽

Vagal Afferent ◽

Glucagon Like Peptide 1

Gut microbiota play an important role in maintaining intestinal health and are involved in the metabolism of carbohydrates, lipids, and amino acids. Recent studies have shown that the central nervous system (CNS) and enteric nervous system (ENS) can interact with gut microbiota to regulate nutrient metabolism. The vagal nerve system communicates between the CNS and ENS to control gastrointestinal tract functions and feeding behavior. Vagal afferent neurons also express receptors for gut peptides that are secreted from enteroendocrine cells (EECs), such as cholecystokinin (CCK), ghrelin, leptin, peptide tyrosine tyrosine (PYY), glucagon-like peptide-1 (GLP-1), and 5-hydroxytryptamine (5-HT; serotonin). Gut microbiota can regulate levels of these gut peptides to influence the vagal afferent pathway and thus regulate intestinal metabolism via the microbiota-gut-brain axis. In addition, bile acids, short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and Immunoglobulin A (IgA) can also exert metabolic control through the microbiota-gut-liver axis. This review is mainly focused on the role of gut microbiota in neuroendocrine regulation of nutrient metabolism via the microbiota-gut-brain-liver axis.

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Gut Hormones as Potential Therapeutic Targets or Biomarkers of Response in Depression: The Case of Motilin

10.20944/preprints202108.0369.v1 ◽

2021 ◽

Author(s):

Ravi Philip Rajkumar

Keyword(s):

Antidepressant Drug ◽

Gut Hormones ◽

Peptide Hormone ◽

Specific Reference ◽

Gut Peptides ◽

Mechanistic Pathway ◽

Predictors Of Response ◽

Treatment Of Depression ◽

Prevalence Of Depression

Recent research has identified the gut-brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut hormones as potential treatments or predictors of response in depression is examined, with specific reference to the peptide hormone motilin. This possibility is explored through two methods: (a) a conceptual review of the possible links between motilin and depression, including evidence from animal and human research as well as clinical trials, and (b) an analysis of the relationship between a functional polymorphism (rs2281820) of the motilin (MLN) gene and cross-national variations in the prevalence of depression. It was observed that (a) there are several plausible mechanisms, including interactions with diet, monoamine, and neuroendocrine pathways, to suggest that motilin may be relevant to the pathophysiology and treatment of depression, and (b) there was a significant correlation between rs2281820 allele frequencies and the prevalence of depression after correcting for multiple confounding factors. These results suggest that further evaluation of the utility of motilin and related gut peptides as markers of antidepressant response is required, and that these molecular pathways represent potential future mechanisms for antidepressant drug development.

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Potential for Gut Peptide-Based Therapy in Postprandial Hypotension

Nutrients ◽

10.3390/nu13082826 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2826

Author(s):

Malcolm J. Borg ◽

Cong Xie ◽

Christopher K. Rayner ◽

Michael Horowitz ◽

Karen L. Jones ◽

...

Keyword(s):

Cardiovascular Response ◽

Cardiovascular Responses ◽

Caloric Content ◽

Gut Peptides ◽

Small Intestinal Transit ◽

Postprandial Hypotension ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Insulinotropic Peptide

Postprandial hypotension (PPH) is an important and under-recognised disorder resulting from inadequate compensatory cardiovascular responses to meal-induced splanchnic blood pooling. Current approaches to management are suboptimal. Recent studies have established that the cardiovascular response to a meal is modulated profoundly by gastrointestinal factors, including the type and caloric content of ingested meals, rate of gastric emptying, and small intestinal transit and absorption of nutrients. The small intestine represents the major site of nutrient-gut interactions and associated neurohormonal responses, including secretion of glucagon-like peptide-1, glucose-dependent insulinotropic peptide and somatostatin, which exert pleotropic actions relevant to the postprandial haemodynamic profile. This review summarises knowledge relating to the role of these gut peptides in the cardiovascular response to a meal and their potential application to the management of PPH.

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The role of maternal gut hormones in normal pregnancy: fasting plasma active glucagon-like peptide 1 level is a negative predictor of fetal abdomen circumference and maternal weight change

Acta Endocrinologica ◽

10.1530/eje-10-0047 ◽

2010 ◽

Vol 162 (5) ◽

pp. 897-903 ◽

Cited By ~ 15

Author(s):

Georgios Valsamakis ◽

Alexandra Margeli ◽

Nikolaos Vitoratos ◽

Anastassios Boutsiadis ◽

Evangelos G Sakkas ◽

...

Keyword(s):

Insulin Secretion ◽

Fetal Growth ◽

Weight Change ◽

Gut Hormones ◽

First Trimester ◽

Second Trimester ◽

Maternal Weight ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

AbstractObjectiveMaternal weight in pregnancy contributes to a glycemic environment that affects fetal growth. Gut peptides (glucagon-like peptide 1 (GLP1), glucose-dependent insulinotropic peptide (GIP), ghrelin, and peptide YY (PYY)) have been related to insulin sensitivity and secretion, weight control, and adipose tissue metabolism. This study aimed at examining the associations of gut hormones during pregnancy with maternal glucose homeostasis, maternal weight, and fetal growth.MethodsA total of 55 pregnant nonobese, nondiabetic Caucasian women were examined during the three trimesters of pregnancy, and anthropometric measurements, evaluation of fasting maternal plasma GLP1 (active), ghrelin (active), total PYY, total GIP, and a 75-g oral glucose tolerance test were done in them. Homeostasis model assessment (HOMA-R), insulin sensitivity index (ISI), and indices of insulin secretion were calculated. Fetal growth was estimated by ultrasound.ResultsFasting GLP1 increased significantly from the second to the third trimester (P<0.05). Fasting GLP1 correlated positively with high-density lipoprotein cholesterol (r=0.52,P=0.04). At the second trimester, fasting GLP1 levels correlated negatively with fetal abdomen circumference (r=−0.55,P=0.034), birth weight (r=−0.50,P=0.040), HOMA-R (r=−0.65,P=0.001), insulin secretion, and triglycerides. At the first trimester, fasting ghrelin levels correlated negatively with HOMA-R and insulin secretion, and positively with ISI. In backward multiple regression analysis, the first trimester GLP1 levels were the best negative predictors of the second trimester fetal abdomen circumference (β=−0.96,P=0.009). In longitudinal regression model, maternal fat and HOMA-R were the positive predictors of maternal weight change during pregnancy, and fasting GLP1 levels were the negative predictors of maternal weight change during pregnancy.ConclusionsDuring pregnancy, maternal GLP1 might be involved in mechanisms that compensate for the pregnancy-related increase in glycemia and insulin resistance, suggesting a role of this peptide in maternal metabolism and weight and fetal growth.

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Morphological study of the gastrointestinal tract of the snow trout, Schizothorax esocinus (Actinopterygii: Cypriniformes)

Zoologia (Curitiba) ◽

10.3897/zoologia.36.e31791 ◽

2019 ◽

Vol 36 ◽

pp. 1-7

Author(s):

Mohd Y. Bhat ◽

Ashok Channa ◽

Bilal A. Paray ◽

Mohammed K. Al-Sadoon ◽

Irfan A. Rather

Keyword(s):

Gastrointestinal Tract ◽

Intestinal Tract ◽

Rectal Mucosa ◽

Mucosal Surface ◽

Surface Epithelium ◽

Physiological Processes ◽

Macroscopic Structure ◽

Physiological Alterations ◽

Mucosal Folds

The present study aimed to investigate the macroscopic structure of the gastrointestinal tract (GIT) of Schizothorax esocinus Heckel, 1838. The surface architecture of the buccopharynx, oesophagus and the entire intestinal tract of S. esocinus has been examined under scanning electron microscope (SEM) after fixing in 2.5% glutaraldehyde buffered with 0.1 M sodium cacodylate at pH 7.3 for 18–48 hours and post-fixation for two hours at room temperature in 1% osmium tetra oxide buffered at pH 7.3 with 0.1 M cacodylate. The mucosal surface of buccopharynx, esophagus, intestinal bulb, and intestine reveal prominent longitudinal major or primary mucosal folds which are further subdivided into the series of irregular and well-circumscribed folds called minor or secondary folds. However, in the intestinal bulb and intestine, the longitudinal major or primary folds themselves form wavy or zigzagging patterns along the mucosal surface. The fine structure of the surface epithelium further shows that the apical surfaces of the epithelial cells are ped with finger-print like microridges, arranged in various patterns and regularly spaced. The rectal mucosa, on the other hand, displays a highly irregular type of major mucosal folds. The separation can’t be seen between major mucosal folds. A thin film of mucous spread over the mucosal folds and the numerous pores through which mucous cells release their content has also been noted along the rectal mucosa. This investigation suggests the possible role of different digestive organs in relation to feeding, digestion, storage, absorption, and various other physiological processes, thereby providing a knowledge necessary to the understanding of pathological or physiological alterations in both aquaculture and natural environment.

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