ArticleInternational journal of obesity (2005)2014
Gastrointestinal hormonal responses on GPR119 activation in lean and diseased rodent models of type 2 diabetes.
Article in International journal of obesity (2005), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- The Sensory Mechanisms of Nutrient-Induced GLP-1 Secretion.Metabolites · 2022Review
- Oea Signaling Pathways and the Metabolic Benefits of Vertical Sleeve Gastrectomy.Annals of surgery · 2020Article
- Signaling of free fatty acid receptors 2 and 3 differs in colonic mucosa following selective agonism or coagonism by luminal propionate.Neurogastroenterology and motility · 2018Article
- Interactions of Gut Endocrine Cells with Epithelium and Neurons.Comprehensive Physiology · 2018Review
- Bidirectional GPR119 Agonism Requires Peptide YY and Glucose for Activity in Mouse and Human Colon Mucosa.Endocrinology · 2018Article
- Dissecting the Physiology and Pathophysiology of Glucagon-Like Peptide-1.Frontiers in endocrinology · 2018Review
- Agonism of free fatty acid receptors 1 and 4 generates peptide YY-mediated inhibitory responses in mouse colon.British journal of pharmacology · 2017Article
- GPR119, a Major Enteroendocrine Sensor of Dietary Triglyceride Metabolites Coacting in Synergy With FFA1 (GPR40).Endocrinology · 2016Article
- A role of CB1R in inducing θ-rhythm coordination between the gustatory and gastrointestinal insula.Scientific reports · 2016Article
- Bile Acids Trigger GLP-1 Release Predominantly by Accessing Basolaterally Located G Protein-Coupled Bile Acid Receptors.Endocrinology · 2015Article
- Pharmacology and physiology of gastrointestinal enteroendocrine cells.Pharmacology research & perspectives · 2015Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundG protein-coupled receptor 119 (GPR119) has emerged as a potential target for the treatment of type 2 diabetes (T2D) and tool compounds have been critical in the evaluation of GPR119 functions.
methodsWe synthesised a novel small-molecule GPR119 agonist, PSN-GPR119, to study GPR119 signalling activities in cells overexpressing GPR119. We measured GPR119-stimulated peptide hormone release from intestinal loops and oral glucose tolerance in vivo from lean (C57BL/6J mouse or Sprague-Dawley (SD) rat) and diabetic (ob/ob mouse or ZDF rat) models. To evaluate the direct effects of GPR119 agonism on gastrointestinal (GI) tissue, we measured vectorial ion transport (measured as ISC; short-circuit current) across rodent GI mucosae and from normal human colon specimens.
resultsGPR119 activation by PSN-GPR119 increased cAMP accumulation in hGPR119-overexpressing HEK293 cells (EC50, 5.5 nM), stimulated glucagon-like peptide 1 (GLP-1) release from GLUTag cells (EC50, 75 nM) and insulin release from HIT-15 cells (EC50, 90 nM). In vivo, PSN-GPR119 improved glucose tolerance by ~50% in lean mice or rats and ~60% in the diabetic ob/ob mouse or ZDF rat models. Luminal addition of PSN-GPR119 to isolated loops of lean rat small intestine stimulated GLP-1, glucose insulinotropic peptide (GIP) and peptide YY (PYY) release under basal (5 mM) and high glucose (25 mM) conditions. Activation of GPR119 also reduced intestinal ion transport. Apical or basolateral PSN-GPR119 addition (1 μM) to lean or T2D rodent colon mucosae reduced ISC levels via PYY-mediated Y1 receptor agonism. The GPR119 response was glucose sensitive and was abolished by Y1 receptor antagonism. Similarly, in human colon, mucosa PSN-GPR119 acted via a Y1-specific mechanism.
conclusionsOur results show that functional GPR119 responses are similar in lean and diabetic rodent, and human colon; that GPR119 stimulation can result in glucose lowering through release of intestinal peptide hormones and that PSN-GPR119 is a useful tool compound for future studies.
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