Duodenal luminal nutrient sensing

Rønnestad, Ivar; Akiba, Yasutada; Kaji, Izumi; Kaunitz, Jonathan D.

doi:10.1016/j.coph.2014.07.010

Cited by 35 publications

(25 citation statements)

References 59 publications

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“…The duodenum has emerged as a key player in both GI and metabolic diseases as it regulates the passage of food as chyme from the stomach to the small intestine, where nutrients are absorbed 38. Autocrine and paracrine mechanisms in the duodenum are also involved in the mucosal defence to acid and the luminal digestion of nutrients with secretion of bile and pancreatic juice 39. Activation of duodeno-gastric feedback mechanisms by chemical or mechanical triggers influences gastric emptying, with an important role of intestinal or pancreatic hormones including incretins and gastric orexigenic hormones, which also signal to the brain 40.…”

Section: Translational Science Conceptsmentioning

confidence: 99%

Novel concepts in the pathophysiology and treatment of functional dyspepsia

Wauters

Talley

Walker

et al. 2019

Gut

181

171

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Emerging data increasingly point towards the duodenum as a key region underlying the pathophysiology of functional dyspepsia (FD), one of the most prevalent functional GI disorders. The duodenum plays a major role in the control and coordination of gastroduodenal function. Impaired duodenal mucosal integrity and low-grade inflammation have been associated with altered neuronal signalling and systemic immune activation, and these alterations may ultimately lead to dyspeptic symptoms. Likely luminal candidates inducing the duodenal barrier defect include acid, bile, the microbiota and food antigens although no causal association with symptoms has been convincingly demonstrated. Recognition of duodenal pathology in FD will hopefully lead to the discovery of new biomarkers and therapeutic targets, allowing biologically targeted rather than symptom-based therapy. In this review, we summarise the recent advances in the diagnosis and treatment of FD with a focus on the duodenum.

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Section: Translational Science Conceptsmentioning

confidence: 99%

Novel concepts in the pathophysiology and treatment of functional dyspepsia

Wauters

Talley

Walker

et al. 2019

Gut

181

171

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“…Furthermore, a dipeptidyl protease-4 (DPP4) inhibitor, which stabilizes released GLP-2, reduces IND-induced enteropathy and promotes ulcer healing [16]. Since GLP-2 release is associated with luminal nutrient sensing [20], we propose that luminal nutrient-induced GLP-2 release combined with DPP4 inhibition will be a useful therapeutic for the treatment of NSAID-induced enteropathy.…”

Section: Introductionmentioning

confidence: 99%

FFA3 Activation Stimulates Duodenal Bicarbonate Secretion and Prevents NSAID-Induced Enteropathy via the GLP-2 Pathway in Rats

et al. 2017

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Therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enteropathy in humans and experimental animals, a cause of considerable morbidity. Unlike foregut NSAID-associated mucosal lesions, most treatments for this condition are of little efficacy. We propose that the endogenously-released intestinotrophic hormone glucagon-like peptide-2 (GLP-2) prevents the development of NSAID-induced enteropathy. Since the short-chain fatty acid (SCFA) receptor FFA3 is expressed on enteroendocrine L cells and on enteric nerves in the gastrointestinal tract, we further hypothesized that activation of FFA3 on L cells protects the mucosa from injury via GLP-2 release with enhanced duodenal HCO3− secretion. We thus investigated the effects of synthetic selective FFA3 agonists with consequent GLP-2 release on NSAID-induced enteropathy. We measured duodenal HCO3− secretion in isoflurane anesthetized rats in a duodenal loop perfused with the selective FFA3 agonists MQC or AR420626 (AR) while measuring released GLP-2 in the portal vein (PV). Intestinal injury was produced by indomethacin (IND, 10 mg/kg, sc) with or without MQC (1 – 10 mg/kg, ig) or AR (0.01 – 0.1 mg/kg, ig or ip) treatment. Luminal perfusion with MQC or AR (0.1 – 10 μM) dose-dependently augmented duodenal HCO3− secretion accompanied by increased GLP-2 concentrations in the PV. The effect of FFA3 agonists was inhibited by co-perfusion of the selective FFA3 antagonist CF3-MQC (30 μM). AR-induced augmented HCO3− secretion was reduced by iv injection of the GLP-2 receptor antagonist GLP-2(3-33) (3 nmol/kg), or by pretreatment with the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTRinh-172 (1 mg/kg, ip). IND-induced small intestinal ulcers were dose-dependently inhibited by intragastric administration of MQC or AR. GLP-2(3-33) (1 mg/kg, ip) or CF3-MQC (1 mg/kg, ig) reversed AR-associated reduction of IND-induced enteropathy. In contrast, ip injection of AR had no effect on enteropathy. These results suggest that luminal FFA3 activation enhances mucosal defenses and prevents NSAID-induced enteropathy via the GLP-2 pathway. The selective FFA3 agonist may be a potential therapeutic candidate for NSAID-induced enteropathy.

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“…El PepT1 se localiza principalmente en el borde de cepillo de las células epiteliales del intestino (Wang et al, 2017), posee un tamaño de aproximadamente 700 aminoácidos (2100 nucleótidos) en vertebrados superiores, mientras que en la mayoría de los vertebrados inferiores es usualmente más grande (Ostaszewska et al, 2010). Sin embargo, la secuencia de aminoácidos como de nucleótidos son altamente conservadas en comparación con los vertebrados superiores (Ronnestad et al, 2014). Además, posee 12 dominios transmembrana, con los terminales carboxilo y amino en el sitio citoplasmático (Daniel, 2004), y dos isoformas: PepT1a y PepT1b (Bucking y Schulte, 2012).…”

Section: Introductionunclassified

Caracterización de la secuencia del gen de la proteína transportadora de péptidos (PepT1) en alevines de paiche Arapaima gigas

Toledo

Castañeda

Feria

et al. 2019

Rev. investig. vet. Perú

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El objetivo del estudio fue caracterizar el PepT1 del paiche Arapaima gigas mediante herramientas genómicas y proteómicas. Se realizó un análisis transcriptómico y proteómico a partir de secciones del intestino, bazo, hígado y riñón de alevines. El análisis transcriptómico permitió obtener dos secuencias consenso de 357 y 459 pb. Ambos fragmentos presentaron un alto grado de homología (78 y 80%), principalmente con secuencias de nucleótidos codificantes del PepT1 de Scleropages formosus del mismo Orden que el paiche. El análisis proteómico por espectrometría de doble masa MALDI TOF/TOF permitió identificar quince secuencias peptídicas del PepT1 en paiche. Como conclusión se logró caracterizar parcialmente el PepT1 en el intestino del paiche, las cuales podrán ser usadas para posteriores estudios sobre la evaluación de su expresión.

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Duodenal luminal nutrient sensing

Cited by 35 publications

References 59 publications

Novel concepts in the pathophysiology and treatment of functional dyspepsia

Novel concepts in the pathophysiology and treatment of functional dyspepsia

FFA3 Activation Stimulates Duodenal Bicarbonate Secretion and Prevents NSAID-Induced Enteropathy via the GLP-2 Pathway in Rats

Caracterización de la secuencia del gen de la proteína transportadora de péptidos (PepT1) en alevines de paiche Arapaima gigas

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