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

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 790 ◽  
Author(s):  
Cong Xie ◽  
Karen L. Jones ◽  
Christopher K. Rayner ◽  
Tongzhi Wu
Keyword(s):  
Gastric Emptying ◽  
Hormone Secretion ◽  
Gastrointestinal Hormones ◽  
Postprandial Glucose ◽  
Gastrointestinal Hormone ◽  
Postprandial Metabolism ◽  
Secretion Profile ◽  
Meal Ingestion ◽  
Small And Large Intestine

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.

Effects of carbohydrate restriction on postprandial glucose metabolism, β-cell function, gut hormone secretion, and satiety in patients with Type 2 diabetes

2021 ◽  
Vol 320 (1) ◽  
pp. E7-E18
Author(s):  
Mads J. Skytte ◽  
Amirsalar Samkani ◽  
Arne Astrup ◽  
Jan Frystyk ◽  
Jens F. Rehfeld ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Cell Function ◽  
Hormone Secretion ◽  
Postprandial Glucose ◽  
Carbohydrate Restriction ◽  
Β Cell ◽  
Gut Hormone ◽  
Β Cell Function

Dietary carbohydrate restriction may improve the phenotype of Type 2 diabetes (T2D) patients. We aimed to investigate 6 wk of carbohydrate restriction on postprandial glucose metabolism, pancreatic α- and β-cell function, gut hormone secretion, and satiety in T2D patients. Methods In a crossover design, 28 T2D patients (mean HbA1c: 60 mmol/mol) were randomized to 6 wk of carbohydrate-reduced high-protein (CRHP) diet and 6 wk of conventional diabetes (CD) diet (energy-percentage carbohydrate/protein/fat: 30/30/40 vs. 50/17/33). Twenty-four-hour continuous glucose monitoring (CGM) and mixed-meal tests were undertaken and fasting intact proinsulin (IP), 32,33 split proinsulin concentrations (SP), and postprandial insulin secretion rates (ISR), insulinogenic index (IGI), β-cell sensitivity to glucose ( Bup), glucagon, and gut hormones were measured. Gastric emptying was evaluated by postprandial paracetamol concentrations and satiety by visual analog scale ratings. A CRHP diet reduced postprandial glucose area under curve (net AUC) by 60% ( P < 0.001), 24 h glucose by 13% ( P < 0.001), fasting IP and SP concentrations (both absolute and relative to C-peptide, P < 0.05), and postprandial ISR (24%, P = 0.015), while IGI and Bup improved by 31% and 45% (both P < 0.001). The CRHP diet increased postprandial glucagon net AUC by 235% ( P < 0.001), subjective satiety by 18% ( P = 0.03), delayed gastric emptying by 15 min ( P < 0.001), decreased gastric inhibitory polypeptide net AUC by 29% ( P < 0.001), but had no significant effect on glucagon-like-peptide-1, total peptide YY, and cholecystokinin responses. A CRHP diet reduced glucose excursions and improved β-cell function, including proinsulin processing, and increased subjective satiety in patients with T2D.

scholarly journals Role of Bile Acids in the Regulation of Food Intake, and Their Dysregulation in Metabolic Disease

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1104
Author(s):  
Cong Xie ◽  
Weikun Huang ◽  
Richard L. Young ◽  
Karen L. Jones ◽  
Michael Horowitz ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Peptide Yy ◽  
Glycogen Synthesis ◽  
Hormone Secretion ◽  
Gastrointestinal Hormones ◽  
Farnesoid X Receptor ◽  
Gastrointestinal Hormone ◽  
Bile Acid Sequestrants

Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.

Load-dependent effects of duodenal glucose on glycemia, gastrointestinal hormones, antropyloroduodenal motility, and energy intake in healthy men

2007 ◽  
Vol 293 (3) ◽  
pp. E743-E753 ◽  
Author(s):  
Amelia N. Pilichiewicz ◽  
Reawika Chaikomin ◽  
Ixchel M. Brennan ◽  
Judith M. Wishart ◽  
Christopher K. Rayner ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Energy Intake ◽  
Healthy Subjects ◽  
Gastrointestinal Hormones ◽  
Saline Control ◽  
Gastrointestinal Hormone ◽  
Double Blind ◽  
Glucagon Like Peptide 1 ◽  
Glucose Plasma

Gastric emptying is a major determinant of glycemia, gastrointestinal hormone release, and appetite. We determined the effects of different intraduodenal glucose loads on glycemia, insulinemia, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and cholecystokinin (CCK), antropyloroduodenal motility, and energy intake in healthy subjects. Blood glucose, plasma hormone, and antropyloroduodenal motor responses to 120-min intraduodenal infusions of glucose at 1) 1 (“G1”), 2) 2 (“G2”), and 3) 4 (“G4”) kcal/min or of 4) saline (“control”) were measured in 10 healthy males in double-blind, randomized fashion. Immediately after each infusion, energy intake at a buffet meal was quantified. Blood glucose rose in response to all glucose infusions ( P < 0.05 vs. control), with the effect of G4 and G2 being greater than that of G1 ( P < 0.05) but with no difference between G2 and G4. The rises in insulin, GLP-1, GIP, and CCK were related to the glucose load ( r > 0.82, P < 0.05). All glucose infusions suppressed antral ( P < 0.05), but only G4 decreased duodenal, pressure waves ( P < 0.01), resulted in a sustained stimulation of basal pyloric pressure ( P < 0.01), and decreased energy intake ( P < 0.05). In conclusion, variations in duodenal glucose loads have differential effects on blood glucose, plasma insulin, GLP-1, GIP and CCK, antropyloroduodenal motility, and energy intake in healthy subjects. These observations have implications for strategies to minimize postprandial glycemic excursions in type 2 diabetes.

scholarly journals Xenin-25 delays gastric emptying and reduces postprandial glucose levels in humans with and without Type 2 diabetes

2014 ◽  
Vol 306 (4) ◽  
pp. G301-G309 ◽  
Author(s):  
Sara Chowdhury ◽  
Dominic N. Reeds ◽  
Dan L. Crimmins ◽  
Bruce W. Patterson ◽  
Erin Laciny ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Gastric Emptying ◽  
Postprandial Glucose ◽  
Nerve Fibers ◽  
Intense Staining ◽  
Glucose Levels ◽  
Healthy Humans ◽  
Glucagon Like Peptide 1

Xenin-25 (Xen) is a neurotensin-related peptide secreted by a subset of glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine cells. In animals, Xen regulates gastrointestinal function and glucose homeostasis, typically by initiating neural relays. However, little is known about Xen action in humans. This study determines whether exogenously administered Xen modulates gastric emptying and/or insulin secretion rates (ISRs) following meal ingestion. Fasted subjects with normal (NGT) or impaired (IGT) glucose tolerance and Type 2 diabetes mellitus (T2DM; n = 10–14 per group) ingested a liquid mixed meal plus acetaminophen (ACM; to assess gastric emptying) at time zero. On separate occasions, a primed-constant intravenous infusion of vehicle or Xen at 4 (Lo-Xen) or 12 (Hi-Xen) pmol·kg−1·min−1 was administered from zero until 300 min. Some subjects with NGT received 30- and 90-min Hi-Xen infusions. Plasma ACM, glucose, insulin, C-peptide, glucagon, Xen, GIP, and glucagon-like peptide-1 (GLP-1) levels were measured and ISRs calculated. Areas under the curves were compared for treatment effects. Infusion with Hi-Xen, but not Lo-Xen, similarly delayed gastric emptying and reduced postprandial glucose levels in all groups. Infusions for 90 or 300 min, but not 30 min, were equally effective. Hi-Xen reduced plasma GLP-1, but not GIP, levels without altering the insulin secretory response to glucose. Intense staining for Xen receptors was detected on PGP9.5-positive nerve fibers in the longitudinal muscle of the human stomach. Thus Xen reduces gastric emptying in humans with and without T2DM, probably via a neural relay. Moreover, endogenous GLP-1 may not be a major enhancer of insulin secretion in healthy humans under physiological conditions.

scholarly journals Alcohol Intoxication and the Postburn Gastrointestinal Hormonal Response

2019 ◽  
Vol 40 (6) ◽  
pp. 785-791 ◽  
Author(s):  
Juan-Pablo Idrovo ◽  
Jill A Shults ◽  
Brenda J Curtis ◽  
Michael M Chen ◽  
Elizabeth J Kovacs
Keyword(s):  
Burn Injury ◽  
Alcohol Intoxication ◽  
Hormone Secretion ◽  
Gastrointestinal Hormones ◽  
Gastric Inhibitory Polypeptide ◽  
Serum Levels ◽  
Gastrointestinal Hormone ◽  
Hormonal Changes ◽  
Ethanol Intoxication ◽  
Burn Victims

Abstract Gastrointestinal hormones are essential in postburn metabolism. Since near 50% of burn victims test positive for blood alcohol levels at hospital admission and have inferior outcomes compared to nonintoxicated burn patients; we hypothesized that the gastrointestinal hormone secretion is compromised in intoxicated burn victims. To test our theory, we quantified gastrointestinal hormones serum levels in a combine ethanol intoxication and burn injury mouse model. Thus, mice received a daily dose of ethanol for 3 days, rested 4 days, and were given ethanol 3 additional days. Mice underwent 15% TBSA scald burn 30 minutes after their last ethanol dose. Serum samples were collected 24 hours after burn injury. Nonintoxicated burned mice exhibited an increase in glucose, insulin, ghrelin, plasminogen activator inhibitor-1, leptin, and resistin by 1.4-, 3-, 13.5-, 6.2-, 9.4-, and 2.4-fold, respectively, compared to sham vehicle mice (P < .05). Burn injury also reduced serum gastric inhibitory polypeptide (GIP) by 32% compared to sham-injured, vehicle-treated mice. Leptin, resistin, glucagon-like peptide-1, as well as insulin, were not different from sham groups when intoxication preceded burn injury. Nevertheless, in burned mice treated with ethanol, gastric inhibitory polypeptide and glucagon serum levels exhibited a significant fold increase of 3.5 and 4.7, respectively. With these results, we conclude that 24 hours after burn injury, mice developed significant changes in gastrointestinal hormones, along with hyperglycemia. Moreover, the combined insult of burn and ethanol intoxication led to additional hormonal changes that may be attributed to a potential pancreatic dysfunction. Further multiday studies are required to investigate the etiology, behavior, and clinical significance of these hormonal changes.

Appetite reduction and weight loss during antiviral therapy for hepatitis C are associated with impaired gastric emptying and altered gastrointestinal hormone secretion

2010 ◽  
Vol 164 (1) ◽  
pp. 45-46
Author(s):  
Mark Ellrichmann ◽  
Ina D. Boehm ◽  
Peter R. Ritter ◽  
Jens J Holst ◽  
Wolfgang E. Schmidt ◽  
...  
Keyword(s):  
Weight Loss ◽  
Hepatitis C ◽  
Gastric Emptying ◽  
Antiviral Therapy ◽  
Hormone Secretion ◽  
Gastrointestinal Hormone

Characterization of duodenal expression and localization of fatty acid-sensing receptors in humans: relationships with body mass index

2014 ◽  
Vol 307 (10) ◽  
pp. G958-G967 ◽  
Author(s):  
Tanya J. Little ◽  
Nicole J. Isaacs ◽  
Richard L. Young ◽  
Raffael Ott ◽  
Nam Q. Nguyen ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Cell Density ◽  
Energy Intake ◽  
Body Mass ◽  
Hormone Secretion ◽  
Gastrointestinal Hormones ◽  
Inverse Correlation ◽  
Duodenal Mucosa ◽  
Gastrointestinal Hormone ◽  
Glucagon Like Peptide 1

Fatty acids (FAs) stimulate the secretion of gastrointestinal hormones, including cholecystokinin (CCK) and glucagon like peptide-1 (GLP-1), which suppress energy intake. In obesity, gastrointestinal responses to FAs are attenuated. Recent studies have identified a key role for the FA-sensing receptors cluster of differentiation (CD)36, G protein-coupled receptor (GPR)40, GPR120, and GPR119 in mediating gastrointestinal hormone secretion. This study aimed to determine the expression and localization of these receptors in the duodenum of humans and to examine relationships with obesity. Duodenal mucosal biopsies were collected from nine lean [body mass index (BMI): 22 ± 1 kg/m2], six overweight (BMI: 28 ± 1 kg/m2), and seven obese (BMI: 49 ± 5 kg/m2) participants. Absolute levels of receptor transcripts were quantified using RT-PCR, while immunohistochemistry was used for localization. Transcripts were expressed in the duodenum of lean, overweight, and obese individuals with abundance of CD36>>GPR40>GPR120>GPR119. Expression levels of GPR120 ( r = 0.46, P = 0.03) and CD36 ( r = 0.69, P = 0.0004) were directly correlated with BMI. There was an inverse correlation between expression of GPR119 with BMI ( r2 = 0.26, P = 0.016). Immunolabeling studies localized CD36 to the brush border membrane of the duodenal mucosa and GPR40, GPR120, and GPR119 to enteroendocrine cells. The number of cells immunolabeled with CCK ( r = −0.54, P = 0.03) and GLP-1 ( r = −0.49, P = 0.045) was inversely correlated with BMI, such that duodenal CCK and GLP-1 cell density decreased with increasing BMI. In conclusion, CD36, GPR40, GPR120, and GPR119 are expressed in the human duodenum. Transcript levels of duodenal FA receptors and enteroendocrine cell density are altered with increasing BMI, suggesting that these changes may underlie decreased gastrointestinal hormone responses to fat and impaired energy intake regulation in obesity.

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