Release Of Gastrointestinal Hormones Research Articles

Metabolic Effects of Selected Conventional and Alternative Sweeteners: A Narrative Review.

Sugar consumption is known to be associated with a whole range of adverse health effects, including overweight status and type II diabetes mellitus. In 2015, the World Health Organization issued a guideline recommending the reduction of sugar intake. In this context, alternative sweeteners have gained interest as sugar substitutes to achieve this goal without loss of the sweet taste. This review aims to provide an overview of the scientific literature and establish a reference tool for selected conventional sweeteners (sucrose, glucose, and fructose) and alternative sweeteners (sucralose, xylitol, erythritol, and D-allulose), specifically focusing on their important metabolic effects. The results show that alternative sweeteners constitute a diverse group, and each substance exhibits one or more metabolic effects. Therefore, no sweetener can be considered to be inert. Additionally, xylitol, erythritol, and D-allulose seem promising as alternative sweeteners due to favorable metabolic outcomes. These alternative sweeteners replicate the benefits of sugars (e.g., sweetness and gastrointestinal hormone release) while circumventing the detrimental effects of these substances on human health.

Monitoring Food Images After Rectal Surgery To Accelerate Recovery Of Postoperative Bowel Motility: A Quasi-Experimental Study

Objective: Considering the role of nurses in the postoperative care of patients, simple nursing interventions can prevent gastrointestinal motility problems. This study aimed to assess the impact of viewing food images on the recovery of intestinal motility after surgery in patients who were operated for rectal cancer.
 Methods: This quasi-experimental study was carried out with 48 patients who underwent rectal surgery in the general surgery clinic of a university hospital in Türkiye from May 2016 to December 2018. The control group had 25 participants and the experimental group had 23. From the first morning after surgery until defecation, patients in the experimental group were asked to monitor food pictures thrice a day, parallel to their meals. 
 Results: In the experimental group, patients’ first flatus (3.30 ± 1.52, day) and defecation time (4.91 ± 1.27, day) were significantly shorter compared with the first flatus (4.28 ± 1.64, day) and defecation time (5.84 ± 1.40, day) of the control group (respectively; p = 0.037, p = 0.027). 
 Conclusion: Monitoring food images supports the cephalic phase and could be a nursing intervention to speed up intestinal functions by increasing the release of gastrointestinal hormones and activating the parasympathetic nervous system. To accelerate bowel motility after rectal surgery, displaying the food images to the patients is a very simple intervention with low risk and cost and nurses should use it in the care of the patients who underwent surgery because of rectal cancer. It is recommended that further studies examining the effectiveness of monitoring food images on gastrointestinal surgeries should be performed.

Oral glucose has little or no effect on appetite and satiety sensations despite a significant gastrointestinal response.

The effect of oral glucose-induced release of gastrointestinal hormones on satiety and appetite independently of prevailing plasma glucose excursions is unknown. The objective is to investigate the effect of oral glucose on appetite and satiety sensations as compared to isoglycemic IV glucose infusion (IIGI) in healthy volunteers. A crossover study involving two study days for each participant. Nineteen healthy participants (6 women, mean age 55.1 [SD 14.2] years; mean body mass index 26.7 [SD 2.2] kg/m2). Each participant underwent a 3-h 50-g oral glucose tolerance test (OGTT) and, on a subsequent study day, an IIGI mimicking the glucose excursions from the OGTT. On both study days, appetite and satiety were indicated regularly on visual analog scale (VAS), and blood was drawn regularly for measurement of pancreatic and gut hormones. Difference in appetite and satiety sensations during OGTT and IIGI. Circulating concentrations of glucose-dependent insulinotropic polypeptide (P < .0001), glucagon-like peptide 1 (P < .0001), insulin (P < .0001), C-peptide (P < .0001), and neurotensin (P = .003) increased significantly during the OGTT as compared to the IIGI, whereas glucagon responses were similarly suppressed (P = .991). Visual analog scale-assessed ratings of hunger, satiety, fullness, thirst, well-being, and nausea, respectively, were similar during OGTT and IIGI whether assessed as mean 0-3-h values or area under the curves. For both groups, a similar, slow increase in appetite and decrease in satiation were observed. Area under the curve, for prospective food consumption (P = .049) and overall appetite score (P = .044) were slightly lower during OGTT compared to IIGI, whereas mean 0-3-h values were statistically similar for prospective food consumption (P = .053) and overall appetite score (P = .063). Despite eliciting robust responses of appetite-reducing and/or satiety-promoting gut hormones, we found that oral glucose administration has little or no effect on appetite and satiety as compared to an IIGI, not affecting the release of appetite-modulating hormones. ClinicalTrials.gov: NCT01492283 and NCT06064084.

Regulation of hepatic lipid metabolism by intestine epithelium-derived exosomes

Abstract The “gut-liver axis” is critical for the control of hepatic lipid homeostasis, where the intestine affects the liver through multiple pathways, such as nutrient uptake, gastrointestinal hormone release, and gut microbiota homeostasis. Whether intestine-originated exosomes mediate the gut’s influence on liver steatosis remains unknown. Here, we aimed to determine whether intestinal epithelium-derived exosomes (intExos) contribute to the regulation of hepatic lipid metabolism. We found that mouse intExos could be taken up by hepatic cells. Mice fed high-fat diet (HFD) received intExos showed strong resistance to liver steatosis. MicroRNA sequencing of intExos indicated the correlation between miR-21a-5p/miR-145a-5p and hepatic lipid metabolism. Both liver overexpression of miR-21a-5p and intExos containing miR-21a-5p alleviated hepatic steatosis in mice fed with HFD. Mechanistically, miR-21a-5p suppressed the expression of Ccl1 (C-C motif chemokine ligand 1) in macrophages, as well as lipid transport genes Cd36 (cluster of differentiation 36) and Fabp7 (fatty acid binding protein 7) in hepatocytes. Liver-specific inhibition of miR-145a-5p significantly reduced hepatic lipid accumulation in mice fed with HFD through negatively regulating the expression of Btg1 (BTG anti-proliferation factor 1), leading to an increase of stearoyl-CoA desaturase-1 and lipogenesis. Our study demonstrates that intExos regulate hepatic lipid metabolism and non-alcoholic fatty liver disease (NAFLD) progression via miR-21a-5p and miR-145a-5p pathways, providing novel mediators for the gut-liver crosstalk and potential targets for regulating hepatic lipid metabolism.

Assessment of the bound conformation of bombesin to the BB1 and BB2 receptors

Bombesin is an endogenous peptide involved in a wide spectrum of physiological activities ranging from satiety, control of circadian rhythm and thermoregulation in the central nervous system, to stimulation of gastrointestinal hormone release, activation of macrophages and effects on development in peripheral tissues. Actions of the peptide are mediated through the two high affinity G-protein coupled receptors BB1R and BB2R. Under pathophysiological conditions, these receptors are overexpressed in many different types of tumors, such as prostate cancer, breast cancer, small and non-small cell lung cancer and pancreatic cancer. This observation has been used for designing cell markers, but it has not been yet exploited for therapeutical purposes. Despite the enormous biological interest of the peptide, little is known about the stereochemical features that contribute to their activity. On the one hand, mutagenesis studies identified a few receptor residues important for high bombesin affinity and on the other, a few studies focused on the relevance of diverse residues of the peptide for receptor activation. Models of the peptide bound to BB1R and BB2R can be helpful to improve our understanding of the stereochemical features granting bombesin activity. Accordingly, the present study describes the computational process followed to construct such models by means of Steered Molecular Dynamics, using models of the peptide and its receptors. Present results provide new insights into the structure-activity relationships of bombesin and its receptors, as well as render an explanation for the differential binding affinity observed towards BB1R and BB2R. Finally, these models can be further exploited to help for designing novel small molecule peptidomimetics with improved pharmacokinetics profile.

Abstract P407: Increased Secretion Of Glucose Dependent Insulinotropic Polypeptide Is Associated With Postprandial Hypotension In Patients With Parkinson Disease

Postprandial hypotension (PPH) is highly prevalent in Parkinson Disease (PD) and is defined as a sudden and substantial decrease (&gt;20 mm Hg or &gt;10 mm hg) in blood pressure within two hours after ingesting a meal. This condition is associated with syncope and falls. Eating a meal induces significant blood sequestration in the splanchnic circulation through the release of gastrointestinal (GI) hormones. Patients with autonomic dysfunction cannot compensate for these hemodynamic changes, which results in PPH. The purpose of this study is to evaluate if increased secretion of GI hormones, including glucose-dependent insulinotropic polypeptide (GIP), a strong splanchnic vasodilator, contributes to PPH in those with PD. We enrolled 11 PD patients, seven with PPH (PPH+) (age 69±7.65 years old, 72% males, Unified Parkinson’s Disease Rating Scale 29±18.9) and four without PPH (PPH-) (age 67±1.71 years, 75% males, UPDRS 20±15.30). PD PPH+ patients had evidence of autonomic impairment and orthostatic hypotension as defined by a change in systolic blood pressure, (-57±29.23 vs. -7±17.66 mm Hg in PPH). Blood pressure, heart rate, and blood GIP levels were measured before and at 5, 10, 15, 30, 60, 90, 120 min timepoints after 75 gr oral glucose in supine position. There was a time-dependent decrease in blood pressure with a nadir at 30 min (-17±14.30 mmHg vs. -5±17.26 in PPH-). In PD PPH+, peak GIP secretion also occurred at 30 min post-glucose ingestion (315.3±297.9 vs. 69.1±34.8 pmol/L in PPH-). PD PPH+ patients had a greater secretion of C-peptide (2141±1017.81 vs.1540.56±428.77 pmol/L in PPH-) and insulin (1477.78±1572.80 vs. 351.09±141.53 pmol/L in PPH-). These initial results show excessive GIP secretion in PD patients with PPH, suggesting that GIP may contribute to its pathophysiology.

In vitro protein digestion of infant formula manufactured with β-casein-enriched whey

A β-casein enriched whey produced from skim milk using a 2-step microfiltration process was used to manufacture a β-casein enriched infant formula (β-CN+ IF) with about 60% of β-CN in its casein fraction. Bringing the casein composition closer to that of human milk affected gelation properties and in vitro proteolysis in comparison with a control IF with the casein profile of cow milk. β-CN+ IF had a higher buffering capacity and produced a weaker gel during acidification but β-CN+ IF exhibited a lower degree of protein hydrolysis (DH) and slower β-CN proteolysis during in vitro gastric digestion. No marked differences were observed during the intestinal phase. β-CN bioactive peptides were more abundant in the β-CN+ IF digesta. Further investigations are needed to assess the impact of these differences on amino acid absorption, gastrointestinal hormone release and gut microbiota in babies fed with this formula composition.

The Role of D-allulose and Erythritol on the Activity of the Gut Sweet Taste Receptor and Gastrointestinal Satiation Hormone Release in Humans: A Randomized, Controlled Trial

BackgroundGlucose induces the release of gastrointestinal (GI) satiation hormones, such as glucagon-like peptide 1 (GLP-1) and peptide tyrosine tyrosine (PYY), in part via the activation of the gut sweet taste receptor (T1R2/T1R3). ObjectivesThe primary objective was to investigate the importance of T1R2/T1R3 for the release of cholecystokinin (CCK), GLP-1, and PYY in response to D-allulose and erythritol by assessing the effect of the T1R2/T1R3 antagonist lactisole on these responses and as secondary objectives to study the effect of the T1R2/T1R3 blockade on gastric emptying, appetite-related sensations, and GI symptoms. MethodsIn this randomized, controlled, double-blind, crossover study, 18 participants (5 men) with a mean ± SD BMI (in kg/m2) of 21.9 ± 1.7 and aged 24 ± 4 y received an intragastric administration of 25 g D-allulose, 50 g erythritol, or tap water, with or without 450 parts per million (ppm) lactisole, respectively, in 6 different sessions. 13C-sodium acetate was added to all solutions to determine gastric emptying. At fixed time intervals, blood and breath samples were collected, and appetite-related sensations and GI symptoms were assessed. Data were analyzed with linear mixed-model analysis. ResultsD-allulose and erythritol induced a significant release of CCK, GLP-1, and PYY compared with tap water (all PHolm < 0.0001, dz >1). Lactisole did not affect the D-allulose– and erythritol-induced release of CCK, GLP-1, and PYY (all PHolm > 0.1). Erythritol significantly delayed gastric emptying, increased fullness, and decreased prospective food consumption compared with tap water (PHolm = 0.0002, dz = –1.05; PHolm = 0.0190, dz = 0.69; and PHolm = 0.0442, dz = –0.62, respectively). ConclusionsD-allulose and erythritol stimulate the secretion of GI satiation hormones in humans. Lactisole had no effect on CCK, GLP-1, and PYY release, indicating that D-allulose– and erythritol-induced GI satiation hormone release is not mediated via T1R2/T1R3 in the gut.

Colonic Delivery of α-Linolenic Acid by an Advanced Nutrient Delivery System Prolongs Glucagon-Like Peptide-1 Secretion and Inhibits Food Intake in Mice.

ScopeNutrients stimulate the secretion of glucagon‐like peptide‐1 (GLP‐1), an incretin hormone, secreted from enteroendocrine L‐cells which decreases food intake. Thus, GLP‐1 analogs are approved for the treatment of obesity, yet cost and side effects limit their use. L‐cells are mainly localized in the distal ileum and colon, which hinders the utilization of nutrients targeting GLP‐1 secretion. This study proposes a controlled delivery system for nutrients, inducing a prolonged endogenous GLP‐1 release which results in a decrease food intake.Methods and Resultsα‐Linolenic acid (αLA) was loaded into thermally hydrocarbonized porous silicon (THCPSi) particles. In vitro characterization and in vivo effects of αLA loaded particles on GLP‐1 secretion and food intake were studied in mice. A total of 40.4 ± 3.2% of loaded αLA is released from particles into biorelevant buffer over 24 h, and αLA loaded THCPSi significantly increased in vitro GLP‐1 secretion. Single‐dose orally given αLA loaded mesoporous particles increased plasma active GLP‐1 levels at 3 and 4 h and significantly reduced the area under the curve of 24 h food intake in mice.ConclusionsαLA loaded THCPSi particles could be used to endogenously stimulate sustain gastrointestinal hormone release and reduce food intake.

The Function of Gastrointestinal Hormones in Obesity-Implications for the Regulation of Energy Intake.

The global burden of obesity and the challenges of prevention prompted researchers to investigate the mechanisms that control food intake. Food ingestion triggers several physiological responses in the digestive system, including the release of gastrointestinal hormones from enteroendocrine cells that are involved in appetite signalling. Disturbed regulation of gut hormone release may affect energy homeostasis and contribute to obesity. In this review, we summarize the changes that occur in the gut hormone balance during the pre- and postprandial state in obesity and the alterations in the diurnal dynamics of their plasma levels. We further discuss how obesity may affect nutrient sensors on enteroendocrine cells that sense the luminal content and provoke alterations in their secretory profile. Gastric bypass surgery elicits one of the most favorable metabolic outcomes in obese patients. We summarize the effect of different strategies to induce weight loss on gut enteroendocrine function. Although the mechanisms underlying obesity are not fully understood, restoring the gut hormone balance in obesity by targeting nutrient sensors or by combination therapy with gut peptide mimetics represents a novel strategy to ameliorate obesity.

Acute Consumption of Blueberries and Short-Term Blueberry Supplementation Improve Glucose Management and Insulin Levels in Sedentary Subjects.

Background: Blueberries are polyphenol-rich fruits with antioxidant and anti-inflammatory properties. Polyphenols from berries act by blocking digestive enzymes, reshaping gastrointestinal microbiota, and affecting the release of gastrointestinal hormones to regulate insulin dynamics and glucose management. However, most studies use fruit extracts instead of fresh fruit. We aimed to evaluate postprandial glucose management and antioxidant capacity of fresh blueberries consumed acutely or as a six-day supplementation in 10 sedentary subjects. Methods: To evaluate the effect of acute blueberry intake, 150 g of blueberries were consumed together with 150 g of white bread by the subject and blood samples were collected at 0, 30, 60, 90 and 120 min to measure glucose, insulin, and plasma antioxidant capacity. To evaluate supplementation, 150 g of blueberries were provided daily for six days and sample collection was performed at day 7. Results: Acute consumption of blueberries decreased postprandial glucose area under the curve (AUC) and increased insulin levels at 15 min timepoint. Supplementation did not affect glucose levels but decreased insulin levels at 120 min. No changes in antioxidant capacity were observed. Conclusions: Consumption of fresh blueberries improves postprandial glucose management presumably due to actions on the gastrointestinal tract, while supplementation improves insulin sensitivity, probably due antioxidant and anti-inflammatory effects.

Selective release of gastrointestinal hormones induced by an orally active GPR39 agonist

ObjectivesObesity is a complex disease associated with a high risk of comorbidities. Gastric bypass surgery, an invasive procedure with low patient eligibility, is currently the most effective intervention that achieves sustained weight loss. This beneficial effect is attributed to alterations in gut hormone signaling. An attractive alternative is to pharmacologically mimic the effects of bariatric surgery by targeting several gut hormonal axes. The G protein-coupled receptor 39 (GPR39) expressed in the gastrointestinal tract has been shown to mediate ghrelin signaling and control appetite, food intake, and energy homeostasis, but the broader effect on gut hormones is largely unknown. A potent and efficacious GPR39 agonist (Cpd1324) was recently discovered, but the in vivo function was not addressed. Herein we studied the efficacy of the GPR39 agonist, Cpd1324, on metabolism and gut hormone secretion. MethodsBody weight, food intake, and energy expenditure in GPR39 agonist-treated mice and GPR39 KO mice were studied in calorimetric cages. Plasma ghrelin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) levels were measured. Organoids generated from murine and human small intestine and mouse colon were used to study GLP-1 and PYY release. Upon GPR39 agonist administration, dynamic changes in intracellular GLP-1 content were studied via immunostaining and changes in ion transport across colonic mucosa were monitored in Ussing chambers. The G protein activation underlying GPR39-mediated selective release of gut hormones was studied using bioluminescence resonance energy transfer biosensors. ResultsThe GPR39 KO mice displayed a significantly increased food intake without corresponding increases in respiratory exchange ratios or energy expenditure. Oral administration of a GPR39 agonist induced an acute decrease in food intake and subsequent weight loss in high-fat diet (HFD)-fed mice without affecting their energy expenditure. The tool compound, Cpd1324, increased GLP-1 secretion in the mice as well as in mouse and human intestinal organoids, but not in GPR39 KO mouse organoids. In contrast, the GPR39 agonist had no effect on PYY or GIP secretion. Transepithelial ion transport was acutely affected by GPR39 agonism in a GLP-1- and calcitonin gene-related peptide (CGRP)-dependent manner. Analysis of Cpd1324 signaling properties showed activation of Gαq and Gαi/o signaling pathways in L cells, but not Gαs signaling. ConclusionsThe GPR39 agonist described in this study can potentially be used by oral administration as a weight-lowering agent due to its stimulatory effect on GLP-1 secretion, which is most likely mediated through a unique activation of Gα subunits. Thus, GPR39 agonism may represent a novel approach to effectively treat obesity through selective modulation of gastrointestinal hormonal axes.

Is Vegetarianism a Solution for Obesity and NCDs? A Review

Purpose of Review: Obesity is defined as an abnormal fat accumulation associated with disease development risk. The prevalence of obesity and non-communicable diseases (NCDs) continues to increase at a concerning pace. The modern lifestyle requires people to rely on processed foods because of their efficiency and low-cost, which are associated with obesity and NCDs. Vegetarian diet refers to the exclusion of meat, fish, seafood and can also exclude animal products such as dairy and eggs. Therefore, the purpose of this review is to explore vegetarianism as a potential solution for obesity and the development of non-communicable diseases. Recent Findings: Meat intake is also related to unhealthy food groups consumption, contributing to overall poor diet quality. In contrast, vegetarian diets are associated with higher satiety, resulting in less food intake, favoring weight reduction. Lowering the prevalence of NCDs should be a priority, and nutritional interventions are pivotal to accomplish this goal. Summary: Vegetarian diets are associated with weight loss due to: fiber content, lower caloric density, microbiota regulation, and the release of gastrointestinal appetite-regulating hormones. Plant-based eating patterns have demonstrated an overall healthier diet and can be a potential solution for obesity and NCDs’ development.

Enteroendocrine Hormone Secretion and Metabolic Control: Importance of the Region of the Gut Stimulation.

It is now widely appreciated that gastrointestinal function is central to the regulation of metabolic homeostasis. Following meal ingestion, the delivery of nutrients from the stomach into the small intestine (i.e., gastric emptying) is tightly controlled to optimise their subsequent digestion and absorption. The complex interaction of intraluminal nutrients (and other bioactive compounds, such as bile acids) with the small and large intestine induces the release of an array of gastrointestinal hormones from specialised enteroendocrine cells (EECs) distributed in various regions of the gut, which in turn to regulate gastric emptying, appetite and postprandial glucose metabolism. Stimulation of gastrointestinal hormone secretion, therefore, represents a promising strategy for the management of metabolic disorders, particularly obesity and type 2 diabetes mellitus (T2DM). That EECs are distributed distinctively between the proximal and distal gut suggests that the region of the gut exposed to intraluminal stimuli is of major relevance to the secretion profile of gastrointestinal hormones and associated metabolic responses. This review discusses the process of intestinal digestion and absorption and their impacts on the release of gastrointestinal hormones and the regulation of postprandial metabolism, with an emphasis on the differences between the proximal and distal gut, and implications for the management of obesity and T2DM.

The Emerging Role of Gut Dysbiosis in Cardio-metabolic Risk Factors for Heart Failure.

To summarize the recent evidence that supports a role for the gut microbiota, microbiota-derived metabolites, and dysbiosis on cardiovascular risk factors, and to discuss the neuro-cardio-metabolic mechanisms that link gut microbiota and heart failure. There is growing evidence that the gut microbiota communicates with and impacts the cardiovascular system, contributing to the development of heart failure once it becomes out of balance (i.e. gut dysbiosis). The exact mechanisms of how the gut microbiota influences cardiovascular outcomes are not fully understood, but immune dysregulation and disturbance of neuro-enteroendocrine hormones seem to be involved. The disturbances in the gut microbiota influence the progression of several risk factors for heart failure, including atherosclerosis, obesity, diabetes, kidney disease and hypertension. In turn, these conditions also act to regulate the gut microbiota through the deterioration of the integrity of the intestinal barrier and the release of neurotransmitters and gastrointestinal hormones. In normal and healthy physiological conditions, these interactions are homeostatic and tightly controlled. However, a combination of environmental exposures (e.g. antibiotics use and Western diet) and the host's intrinsic conditions (e.g. genetics and fluid status) can result in the breakdown of intestinal homeostasis and further progression of cardiovascular risk factors, which lead to the development of heart failure. Manipulation of the gut microbiota may have the potential to improve cardiovascular outcomes by ameliorating immune system dysregulation, enteroendocrine disruptions, and neurohormonal activation in patients with cardiovascular risk factors for heart failure.

Insulin resistance in bariatric surgery.

To give an updated review on the underlying mechanisms and clinical effects of improved glucose control after bariatric surgery. The basic principles of the mechanism for the metabolic effects of bariatric surgery can be categorized into calorie restriction, deviation of nutrients, and reduced amounts of adipose tissue. Recent findings suggest the importance of early changes following deviation of nutrients to more distal parts of the small bowel resulting in altered release of gastrointestinal hormones, altered gut microbiota, and weight-reduction. In the long-term, loss of adipose tissue results in reduced inflammation and improved insulin sensitivity. From a clinical perspective these changes are associated with remission of diabetes in patients with morbid obesity and type 2 diabetes, prevention of diabetes in patients with insulin resistance without overt type 2 diabetes and prevention of both microvascular and macrovascular complications for all patients with morbid obesity. At present, bariatric surgery remains the most effective treatment option to improve glucose control and long-term complications associated with hyperglycemia in patients with obesity.Although the mechanisms behind these metabolic effects remain only partially understood, further knowledge on these complex mechanisms may help identifying durable treatment options for morbid obesity and important metabolic comorbidities.

Intragastric administration of the bitter tastant quinine lowers the glycemic response to a nutrient drink without slowing gastric emptying in healthy men.

The rate of gastric emptying and the release of gastrointestinal (GI) hormones are major determinants of postprandial blood-glucose concentrations and energy intake. Preclinical studies suggest that activation of GI bitter-taste receptors potently stimulates GI hormones, including glucagon-like peptide-1 (GLP-1), and thus may reduce postprandial glucose and energy intake. We evaluated the effects of intragastric quinine on the glycemic response to, and the gastric emptying of, a mixed-nutrient drink and the effects on subsequent energy intake in healthy men. The study consisted of 2 parts: part A included 15 lean men, and part B included 12 lean men (aged 26 ± 2 yr). In each part, participants received, on 3 separate occasions, in double-blind, randomized fashion, intragastric quinine (275 or 600 mg) or control, 30 min before a mixed-nutrient drink (part A) or before a buffet meal (part B). In part A, plasma glucose, insulin, glucagon, and GLP-1 concentrations were measured at baseline, after quinine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured. In part B, energy intake at the buffet meal was quantified. Quinine in 600 mg (Q600) and 275 mg (Q275) doses alone stimulated insulin modestly (P < 0.05). After the drink, Q600 and Q275 reduced plasma glucose and stimulated insulin (P < 0.05), Q275 stimulated GLP-1 (P < 0.05), and Q600 tended to stimulate GLP-1 (P = 0.066) and glucagon (P = 0.073) compared with control. Quinine did not affect gastric emptying of the drink or energy intake. In conclusion, in healthy men, intragastric quinine reduces postprandial blood glucose and stimulates insulin and GLP-1 but does not slow gastric emptying or reduce energy intake under our experimental conditions.

Metabolic control via nutrient-sensing mechanisms: role of taste receptors and the gut-brain neuroendocrine axis.

Nutrient sensing plays an important role in ensuring that appropriate digestive or hormonal responses are elicited following the ingestion of fuel substrates. Mechanisms of nutrient sensing in the oral cavity have been fairly well characterized and involve lingual taste receptors. These include heterodimers of G protein-coupled receptors (GPCRs) of the taste receptor type 1 (T1R) family for sensing sweet (T1R2-T1R3) and umami (T1R1-T1R3) stimuli, the T2R family for sensing bitter stimuli, and ion channels for conferring sour and salty tastes. In recent years, several studies have revealed the existence of additional nutrient-sensing mechanisms along the gastrointestinal tract. Glucose sensing is achieved by the T1R2-T1R3 heterodimer on enteroendocrine cells, which plays a role in triggering the secretion of incretin hormones for improved glycemic and lipemic control. Protein hydrolysates are detected by Ca2+-sensing receptor, the T1R1-T1R3 heterodimer, and G protein-coupled receptor 92/93 (GPR92/93), which leads to the release of the gut-derived satiety factor cholecystokinin. Furthermore, several GPCRs have been implicated in fatty acid sensing: GPR40 and GPR120 respond to medium- and long-chain fatty acids, GPR41 and GPR43 to short-chain fatty acids, and GPR119 to endogenous lipid derivatives. Aside from the recognition of fuel substrates, both the oral cavity and the gastrointestinal tract also possess T2R-mediated mechanisms of recognizing nonnutrients such as environmental contaminants, bacterial toxins, and secondary plant metabolites that evoke a bitter taste. These gastrointestinal sensing mechanisms result in the transmission of neuronal signals to the brain through the release of gastrointestinal hormones that act on vagal and enteric afferents to modulate the physiological response to nutrients, particularly satiety and energy homeostasis. Modulating these orally accessible nutrient-sensing pathways using particular foods, dietary supplements, or pharmaceutical compounds may have therapeutic potential for treating obesity and metabolic diseases.

Effects of Intraduodenal Infusion of the Bitter Tastant, Quinine, on Antropyloroduodenal Motility, Plasma Cholecystokinin, and Energy Intake in Healthy Men.

Background/AimsNutrient-induced gut hormone release (eg, cholecystokinin [CCK]) and the modulation of gut motility (particularly pyloric stimulation) contribute to the regulation of acute energy intake. Non-caloric bitter compounds, including quinine, have recently been shown in cell-line and animal studies to stimulate the release of gastrointestinal hormones by activating bitter taste receptors expressed throughout the gastrointestinal tract, and thus, may potentially suppress energy intake without providing additional calories. This study aims to evaluate the effects of intraduodenally administered quinine on antropyloroduodenal pressures, plasma CCK and energy intake.MethodsFourteen healthy, lean men (25 ± 5 years; BMI: 22.5 ± 2.0 kg/m2) received on 4 separate occasions, in randomized, double-blind fashion, 60-minute intraduodenal infusions of quinine hydrochloride at doses totaling 37.5 mg (“Q37.5”), 75 mg (“Q75”) or 225 mg (“Q225”), or control (all 300 mOsmol). Antropyloroduodenal pressures (high-resolution manometry), plasma CCK (radioimmunoassay), and appetite perceptions/gastrointestinal symptoms (visual analog questionnaires) were measured. Ad libitum energy intake (buffet-meal) was quantified immediately post-infusion. Oral quinine taste-thresholds were assessed on a separate occasion using 3-alternative forced-choice procedure.ResultsAll participants detected quinine orally (detection-threshold: 0.19 ± 0.07 mmol/L). Intraduodenal quinine did not affect antral, pyloric or duodenal pressures, plasma CCK (pmol/L [peak]; control: 3.6 ± 0.4, Q37.5: 3.6 ± 0.4, Q75: 3.7 ± 0.3, Q225: 3.9 ± 0.4), appetite perceptions, gastrointestinal symptoms or energy intake (kcal; control: 1088 ± 90, Q37.5: 1057 ± 69, Q75: 1029 ±70, Q225: 1077 ± 88).ConclusionQuinine, administered intraduodenally over 60 minutes, even at moderately high doses, but low infusion rates, does not modulate appetite-related gastrointestinal functions or energy intake.

Acupoint Massage Can Effectively Promote the Recovery of Gastrointestinal Function after Gynecologic Laparoscopy

Objective: To investigate the effect of acupoint massage on the recovery of gastrointestinal function in patients after laparoscopic surgery for gynecologic indications. Methods: A total of 160 patients, who underwent gynecologic laparoscopy from December 2015 to January 2017, were recruited. Half of the patients received standard postoperative nursing (i.e., the control group); while the other half received acupoint massage in addition to the standard care (i.e., the observation group). The recovery time of bowel sounds, the first anal exhaust time and the first defecation time were recorded. The plasma levels of motilin, somatostatin and cholecystokinin before and after the surgery were also determined. Results: Compared to the control group, the observation group demonstrated significantly shorter bowel sound recovery time, first anal exhaust time and first defecation time (t = 11.755, 10.400, 11.950, P < 0.01 for all comparisons). Before surgery, the plasma levels of gastrointestinal hormones in both groups were comparable. At 12, 24, and 48 hours postoperative, the difference between two groups was statistically significant (P < 0.05). The overall response rate of the observation group was also significantly higher than that of the control group (control group, 78.75%; observation group, 97.50%; P = 0.008). Conclusion: Acupoint massage could accelerate the recovery of bowel function after gynecologic laparoscopy by modulating the release of gastrointestinal hormones