754 results match your criteria tract incretin


Actions of GLP-1 receptor ligands in the gut.

Br J Pharmacol 2021 Jul 7. Epub 2021 Jul 7.

Department of Biomedical Sciences and NovoNordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen.

The incretin hormone glucagon-like peptide-1 (GLP-1) is inactivated by the enzyme DPP-4 even before it leaves the gut but seems to act predominantly via activation of intestinal sensory neurons expressing the GLP-1 receptor. Thus activation of vagal afferents is probably responsible for its effects on appetite and food intake, gastrointestinal secretion and motility, and pancreatic endocrine secretion. However, GLP-1 receptors are widely expressed in the gastrointestinal tract, including epithelial cells in the stomach, and the Brunner glands, in endocrine cells of the gut epithelium, and on mucosal lymphocytes. Read More

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Single-Cell Mapping of GLP-1 and GIP Receptor Expression in the Dorsal Vagal Complex.

Diabetes 2021 Jun 27. Epub 2021 Jun 27.

Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark

The dorsal vagal complex (DVC) in the hindbrain, composed of the area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus, plays a critical role in modulating satiety. The incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) act directly in the brain to modulate feeding, and receptors for both are expressed in the DVC. Given the impressive clinical responses to pharmacologic manipulation of incretin signaling, understanding the central mechanisms by which incretins alter metabolism and energy balance is of critical importance. Read More

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Therapeutic potential of targeting intestinal bitter taste receptors in diabetes associated with dyslipidemia.

Authors:
Wen-Ling Chou

Pharmacol Res 2021 May 26;170:105693. Epub 2021 May 26.

Scientific Development Department, Full Universe MedComms Ltd., Taipei 106, Taiwan; Herbal Sciences Program, Bastyr University, Seattle, WA, USA. Electronic address:

Intestinal release of incretin hormones after food intake promotes glucose-dependent insulin secretion and regulates glucose homeostasis. The impaired incretin effects observed in the pathophysiologic abnormality of type 2 diabetes have triggered the pharmacological development of incretin-based therapy through the activation of glucagon-like peptide-1 (GLP-1) receptor, including GLP-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 (DPP4) inhibitors. In the light of the mechanisms involved in the stimulation of GLP-1 secretion, it is a fundamental question to explore whether glucose and lipid homeostasis can be manipulated by the digestive system in response to nutrient ingestion and taste perception along the gastrointestinal tract. Read More

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Efficacy and safety of ipragliflozin in Japanese patients with type 2 diabetes and inadequate glycaemic control on sitagliptin.

Diabetes Obes Metab 2021 May 25. Epub 2021 May 25.

Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.

Aims: To assess the efficacy, safety and tolerability of ipragliflozin 50 mg once daily added to sitagliptin 50 mg once daily monotherapy in Japanese patients with type 2 diabetes (T2D).

Materials And Methods: The results of two clinical trials are reported. In both trials, patients had glycated haemoglobin (HbA1c) levels of 7. Read More

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The Amount of Residual Incretin Regulates the Pancreatic β-cell Function and Glucose Homeostasis.

Intern Med 2021 1;60(9):1433-1442. Epub 2021 May 1.

Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Japan.

The gastrointestinal tract is considered an important endocrine organ for controlling glucose homeostasis via the production of incretins. A 21-year-old man emergently underwent total colectomy due to severe ulcerative colitis, and overt diabetes became evident. Weekly administration of a glucagon-like peptide (GLP)-1 receptor agonist (RA) dramatically improved his glucose control. Read More

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Exploring the GLP-1-GLP-1R axis in porcine pancreas and gastrointestinal tract in vivo by ex vivo autoradiography.

BMJ Open Diabetes Res Care 2021 04;9(1)

Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.

Introduction: Glucagon-like peptide-1 (GLP-1) increases insulin secretion from pancreatic beta-cells and GLP-1 receptor (GLP-1R) agonists are widely used as treatment for type 2 diabetes mellitus. Studying occupancy of the GLP-1R in various tissues is challenging due to lack of quantitative, repeatable assessments of GLP-1R density. The present study aimed to describe the quantitative distribution of GLP-1Rs and occupancy by endogenous GLP-1 during oral glucose tolerance test (OGTT) in pigs, a species that is used in biomedical research to model humans. Read More

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Gut-Based Strategies to Reduce Postprandial Glycaemia in Type 2 Diabetes.

Front Endocrinol (Lausanne) 2021 9;12:661877. Epub 2021 Apr 9.

Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.

Postprandial glycemic control is an important target for optimal type 2 diabetes management, but is often difficult to achieve. The gastrointestinal tract plays a major role in modulating postprandial glycaemia in both health and diabetes. The various strategies that have been proposed to modulate gastrointestinal function, particularly by slowing gastric emptying and/or stimulating incretin hormone GLP-1, are summarized in this review. Read More

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GPR119 agonists for the treatment of type 2 diabetes: an updated patent review (2014-present).

Expert Opin Ther Pat 2021 May 10:1-14. Epub 2021 May 10.

College of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, China.

: Type 2 diabetes is a rapid-growing complex chronic metabolic disease characterized by hyperglycemia due to lessened insulin secretion, insulin resistance and hepatic glucose overproduction. GPR119 is a class A of G protein-coupled receptor, expressed on certain enteroendocrine L and K cells in the small intestine and by β-cells within the islets of Langerhans of the pancreas. Activation of GPR119 stimulates the secretion of glucagon-like peptide-1 (GLP-1) in the intestinal tract and glucose-dependent release of insulin in pancreatic β-cells. Read More

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Short-, medium-, and long-chain fatty acid profiles and signaling is responsive to dietary phytase and lactic acid treatment of cereals along the gastrointestinal tract of growing pigs.

J Anim Sci 2021 Jun;99(6)

Institute of Food Research and Product Development, University of Kasetsart, Bangkok, Thailand.

Dietary and microbially derived fatty acids (FA) play important roles in gut mucosal inflammatory signaling, barrier function, and oxidative stress response. Nevertheless, little information is available about gastrointestinal FA profiles and receptor distribution in pigs, especially for long-chain FA (LCFA). Therefore, the present pilot study aimed to (1) investigate the gastrointestinal FA profiles; (2) link the luminal FA profiles to the mucosal expression of genes related to FA sensing and signaling; and (3) assess potential dietary effects on gut and systemic lipid metabolism in pigs. Read More

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Metabolic responses and benefits of glucagon-like peptide-1 (GLP-1) receptor ligands.

Br J Pharmacol 2021 Apr 6. Epub 2021 Apr 6.

Diabetes Research Group, Ulster University, Coleraine, UK.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has undergone a revolutionary turnaround from discovery to clinically approved therapeutic. Rapid progress in drug design and formulation has led from initial development of short- and long-acting drugs suitable for daily or weekly parenteral administration, respectively, through to the most recent approval of an orally active GLP-1 agent. The current review outlines the biological action profile of GLP-1 including the various beneficial metabolic responses in pancreatic and extra-pancreatic tissues, including the gastrointestinal tract, liver, bone and kidney as well as the reproductive cardiovascular and CNS. Read More

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Nutrient-Induced Cellular Mechanisms of Gut Hormone Secretion.

Nutrients 2021 Mar 9;13(3). Epub 2021 Mar 9.

Wellcome Trust-MRC Institute of Metabolic Science Metabolic Research Laboratories, Cambridge University, Addenbrookes Hospital, Cambridge CB2 0QQ, UK.

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. Read More

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Ghrelin and Glucagon-Like Peptide-1: A Gut-Brain Axis Battle for Food Reward.

Nutrients 2021 Mar 17;13(3). Epub 2021 Mar 17.

Human & Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.

Eating behaviors are influenced by the reinforcing properties of foods that can favor decisions driven by reward incentives over metabolic needs. These food reward-motivated behaviors are modulated by gut-derived peptides such as ghrelin and glucagon-like peptide-1 (GLP-1) that are well-established to promote or reduce energy intake, respectively. In this review we highlight the antagonizing actions of ghrelin and GLP-1 on various behavioral constructs related to food reward/reinforcement, including reactivity to food cues, conditioned meal anticipation, effort-based food-motivated behaviors, and flavor-nutrient preference and aversion learning. Read More

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Dietary Influences on the Microbiota-Gut-Brain Axis.

Int J Mol Sci 2021 Mar 28;22(7). Epub 2021 Mar 28.

Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Clifford Bridge Road, Coventry CV2 2DX, UK.

Over unimaginable expanses of evolutionary time, our gut microbiota have co-evolved with us, creating a symbiotic relationship in which each is utterly dependent upon the other. Far from confined to the recesses of the alimentary tract, our gut microbiota engage in complex and bi-directional communication with their host, which have far-reaching implications for overall health, wellbeing and normal physiological functioning. Amongst such communication streams, the microbiota-gut-brain axis predominates. Read More

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Irisin and Incretin Hormones: Similarities, Differences, and Implications in Type 2 Diabetes and Obesity.

Biomolecules 2021 02 15;11(2). Epub 2021 Feb 15.

Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, I-70124 Bari, Italy.

Incretins are gut hormones that potentiate glucose-stimulated insulin secretion (GSIS) after meals. Glucagon-like peptide-1 (GLP-1) is the most investigated incretin hormone, synthesized mainly by L cells in the lower gut tract. GLP-1 promotes β-cell function and survival and exerts beneficial effects in different organs and tissues. Read More

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February 2021

Central and peripheral GLP-1 systems independently suppress eating.

Nat Metab 2021 02 15;3(2):258-273. Epub 2021 Feb 15.

Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.

The anorexigenic peptide glucagon-like peptide-1 (GLP-1) is secreted from gut enteroendocrine cells and brain preproglucagon (PPG) neurons, which, respectively, define the peripheral and central GLP-1 systems. PPG neurons in the nucleus tractus solitarii (NTS) are widely assumed to link the peripheral and central GLP-1 systems in a unified gut-brain satiation circuit. However, direct evidence for this hypothesis is lacking, and the necessary circuitry remains to be demonstrated. Read More

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February 2021

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

Molecules 2021 Jan 29;26(3). Epub 2021 Jan 29.

Department of Human Nutrition, Foods and Exercise, College of Agricultural and Life Sciences, Virginia Tech, Blacksburg, VA 24060, USA.

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. Read More

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January 2021

A randomized, placebo-controlled trial to assess the efficacy and safety of sitagliptin in Japanese patients with type 2 diabetes and inadequate glycaemic control on ipragliflozin.

Diabetes Obes Metab 2021 06 28;23(6):1342-1350. Epub 2021 Feb 28.

Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey, USA.

Aims: To investigate the efficacy, safety and tolerability of sitagliptin 50 mg once daily added to ipragliflozin 50 mg once daily monotherapy in Japanese patients with type 2 diabetes (T2D).

Materials And Methods: Japanese patients with T2D and glycated haemoglobin (HbA1c) 7.0% to 10. Read More

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Disentangling conflicting evidence on DPP-4 inhibitors and outcomes of COVID-19: narrative review and meta-analysis.

J Endocrinol Invest 2021 Jul 29;44(7):1379-1386. Epub 2021 Jan 29.

Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy.

Background: The infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread all over the world, becoming pandemic. Several studies have shown that diabetes mellitus (DM) is an independent risk factor that increases mortality and other adverse outcomes of coronavirus disease-19 (COVID-19). Studies have suggested that SARS-CoV-2 may bind dipeptidyl peptidase-4 (DPP4) for entering cells of the respiratory tract. Read More

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Targeting lipid GPCRs to treat type 2 diabetes mellitus - progress and challenges.

Nat Rev Endocrinol 2021 03 25;17(3):162-175. Epub 2021 Jan 25.

Montreal Diabetes Research Center, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.

Therapeutic approaches to the treatment of type 2 diabetes mellitus that are designed to increase insulin secretion either directly target β-cells or indirectly target gastrointestinal enteroendocrine cells (EECs), which release hormones that modulate insulin secretion (for example, incretins). Given that β-cells and EECs both express a large array of G protein-coupled receptors (GPCRs) that modulate insulin secretion, considerable research and development efforts have been undertaken to design therapeutic drugs targeting these GPCRs. Among them are GPCRs specific for free fatty acid ligands (lipid GPCRs), including free fatty acid receptor 1 (FFA1, otherwise known as GPR40), FFA2 (GPR43), FFA3 (GPR41) and FFA4 (GPR120), as well as the lipid metabolite binding glucose-dependent insulinotropic receptor (GPR119). Read More

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Metabolic Messengers: glucagon-like peptide 1.

Nat Metab 2021 02 11;3(2):142-148. Epub 2021 Jan 11.

Wellcome Trust MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

Glucagon like peptide-1 (GLP-1), a peptide hormone from the intestinal tract, plays a central role in the coordination of postprandial glucose homeostasis through actions on insulin secretion, food intake and gut motility. GLP-1 forms the basis for a variety of current drugs for the treatment of type 2 diabetes and obesity, as well as new agents currently being developed. Here, we provide a concise overview of the core physiology of GLP-1 secretion and action, and the role of the peptide in human health, disease and therapeutics. Read More

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February 2021

Mechanisms controlling pancreatic islet cell function in insulin secretion.

Nat Rev Mol Cell Biol 2021 02 4;22(2):142-158. Epub 2021 Jan 4.

Sarah W. Stedman Nutrition and Metabolism Center and Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.

Metabolic homeostasis in mammals is tightly regulated by the complementary actions of insulin and glucagon. The secretion of these hormones from pancreatic β-cells and α-cells, respectively, is controlled by metabolic, endocrine, and paracrine regulatory mechanisms and is essential for the control of blood levels of glucose. The deregulation of these mechanisms leads to various pathologies, most notably type 2 diabetes, which is driven by the combined lesions of impaired insulin action and a loss of the normal insulin secretion response to glucose. Read More

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February 2021

[Gut microbiota is a factor of risk for obesity and type 2 diabetes].

Ter Arkh 2020 Nov 24;92(10):97-104. Epub 2020 Nov 24.

Pirogov Russian National Research Medical University.

Gut microbiota (GM) is a set of bacteria which colonize the gastrointestinal tract. GM and its active metabolites take part in intestinal and hepatic gluconeogenesis, in the synthesis of incretin hormones, and affect the regulation of appetite. Thus, GM and its metabolites participate in the homeostasis of carbohydrates and fats. Read More

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November 2020

Modulation of Food Intake by Differential TAS2R Stimulation in Rat.

Nutrients 2020 Dec 10;12(12). Epub 2020 Dec 10.

MoBioFood Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain.

Metabolic surgery modulates the enterohormone profile, which leads, among other effects, to changes in food intake. Bitter taste receptors (TAS2Rs) have been identified in the gastrointestinal tract and specific stimulation of these has been linked to the control of ghrelin secretion. We hypothesize that optimal stimulation of TAS2Rs could help to modulate enteroendocrine secretions and thus regulate food intake. Read More

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December 2020

Leptin suppresses development of GLP-1 inputs to the paraventricular nucleus of the hypothalamus.

Elife 2020 11 18;9. Epub 2020 Nov 18.

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, United States.

The nucleus of the solitary tract (NTS) is critical for the central integration of signals from visceral organs and contains preproglucagon (PPG) neurons, which express leptin receptors in the mouse and send direct projections to the paraventricular nucleus of the hypothalamus (PVH). Here, we visualized projections of PPG neurons in leptin-deficient mice and found that projections from PPG neurons are elevated compared with controls, and PPG projections were normalized by targeted rescue of leptin receptors in mice, which lack functional neuronal leptin receptors. Moreover, and mice displayed increased levels of neuronal activation in the PVH following vagal stimulation, and whole-cell patch recordings of GLP-1 receptor-expressing PVH neurons revealed enhanced excitatory neurotransmission, suggesting that leptin acts cell autonomously to suppress representation of excitatory afferents from PPG neurons, thereby diminishing the impact of visceral sensory information on GLP-1 receptor-expressing neurons in the PVH. Read More

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November 2020

Long-term inhibition of dipeptidyl-peptidase 4 reduces islet infiltration and downregulates IL-1β and IL-12 in NOD mice.

Int Immunopharmacol 2020 Nov 23;88:106945. Epub 2020 Sep 23.

Department of Endocrinology, The Second Affiliated Hospital of Guangzhou Medical University, The East Chang-Gang Road, Guangzhou, China. Electronic address:

Dipeptidyl-peptidase 4 (DPP-4) inhibitor (sitagliptin) is a novel anti-hyperglycemia drug in the treatment of type 2 diabetes. However, its potential in type 1 diabetes is still unclear. Recent studies show that increased infection, especially respiratory tract infection, is significantly associated with DPP-4 inhibitors. Read More

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November 2020

Glucagon-Like Peptide-1 (GLP-1) in the Integration of Neural and Endocrine Responses to Stress.

Nutrients 2020 Oct 28;12(11). Epub 2020 Oct 28.

Laboratory of Endocrinology, Biomedical Research Center (CINBIO), University of Vigo, 36310 Vigo, Spain.

Glucagon like-peptide 1 (GLP-1) within the brain is produced by a population of preproglucagon neurons located in the caudal nucleus of the solitary tract. These neurons project to the hypothalamus and another forebrain, hindbrain, and mesolimbic brain areas control the autonomic function, feeding, and the motivation to feed or regulate the stress response and the hypothalamic-pituitary-adrenal axis. GLP-1 receptor (GLP-1R) controls both food intake and feeding behavior (hunger-driven feeding, the hedonic value of food, and food motivation). Read More

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October 2020

Functional interaction between Ghrelin and GLP-1 regulates feeding through the vagal afferent system.

Sci Rep 2020 10 28;10(1):18415. Epub 2020 Oct 28.

Division of Neurology, Respirology, Endocrinology, and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.

The gastrointestinal tract transmits feeding-regulatory signals to the brain via neuronal and hormonal pathways. Here we studied the interaction between the orexigenic gastric peptide, ghrelin, and the anorectic intestinal peptide, glucagon-like peptide 1 (GLP-1), in terms of feeding regulation via the vagal afferents. GLP-1 preadministration 30 min before ghrelin administration to rats and mice abolished ghrelin-induced food intake, while ghrelin preadministration abolished the anorectic effect of GLP-1. Read More

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October 2020

Effects of passage through the digestive tract on incretin secretion: Before and after birth.

J Diabetes Investig 2021 Jun 28;12(6):970-977. Epub 2020 Nov 28.

Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Aims/introduction: It was reported that fetuses secrete endogenous incretin; however, the stimulants of fetal incretin secretion are not fully understood. To investigate the association between the passage of amniotic fluid through the intestinal tract and fetal secretion of incretin, we analyzed umbilical cord incretin levels of infants with duodenum atresia.

Materials And Methods: Infants born from July 2017 to July 2019 (infants with duodenum atresia and normal term or preterm infants) were enrolled. Read More

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Expression of serotonin receptor HTR4 in glucagon-like peptide-1-positive enteroendocrine cells of the murine intestine.

Pflugers Arch 2020 10 1;472(10):1521-1532. Epub 2020 Sep 1.

Research Faculty of Agriculture, Hokkaido University, Sapporo, 060-8589, Japan.

Serotonin (5-hydroxytryptamine [5-HT]) synthesized and released in enterochromaffin (EC) cells participates in various functions in the gastrointestinal tract by acting on a diverse range of 5-HT receptors (HTRs) expressed on smooth muscle, enteric neurons, and epithelial cells. We previously observed that genes encoding HTR2A, HTR2B, and HTR4 are expressed in murine intestinal organoids, suggesting the expression of these HTRs in intestinal epithelial cells. The present study investigated the localization of these HTRs in the murine intestine by immunofluorescence staining. Read More

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October 2020

A Pilot Study Examining the Effects of GLP-1 Receptor Blockade Using Exendin-(9,39) on Gastric Emptying and Caloric Intake in Subjects With and Without Bariatric Surgery.

Metab Syndr Relat Disord 2020 11 20;18(9):406-412. Epub 2020 Aug 20.

Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA.

Obesity causes significant morbidity and mortality and continues to be a significant public health concern. Unfortunately, lifestyle modification and pharmacotherapy do not produce durable results. This has led to bariatric surgical procedures playing an increasingly prominent role in the management of medically complicated obesity. Read More

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November 2020