ArticleDiabetologia2013
Oligopeptides stimulate glucagon-like peptide-1 secretion in mice through proton-coupled uptake and the calcium-sensing receptor.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 190 citations in OpenAlex.
- The Postprandial Glycaemic and Hormonal Responses Following the Ingestion of a Novel, Ready-to-Drink Shot Containing a Low Dose of Whey Protein in Centrally Obese and Lean Adult Males: A Randomised Controlled Trial.Frontiers in endocrinology · 2021Trial
- Trial
- Glucagon-Like Peptide-1 Agonists and Blood Pressure Regulation: Molecular Mechanisms and Cardiovascular Implications.Pharmacology research & perspectives · 2026Review
- From Food Structure to L-Cell Exposure: How Processing and Digestion Shape Endogenous GLP-1 Responses.Molecules (Basel, Switzerland) · 2026Review
- L-cell-specificActa pharmaceutica Sinica. B · 2026Article
- Food-Derived Antidiabetic Peptides as Multi-Target Systemic Regulators: A Comprehensive Review of Sources, Preparation, Mechanisms and Future Perspectives.Foods (Basel, Switzerland) · 2026Review
- A genetic screen in enteroendocrine cells reveals mechanisms that control protein sensing and GLP-1 release.bioRxiv : the preprint server for biology · 2026Article
- The Enteric Neuronal Circuitry: A Key Ignored Player in Nutrient Sensing Along the Gut-Brain Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- GLP-1-based therapies for type 2 diabetes: from single, dual and triple agonists to endogenous GLP-1 production and L-cell differentiation.Diabetology & metabolic syndrome · 2025Review
- Glucagon-Like Peptide-1 Links Ingestion, Homeostasis, and the Heart.Comprehensive Physiology · 2025Review
- L-valine is a powerful stimulator of GLP-1 secretion in rodents and stimulates secretion through ATP-sensitive potassium channels and voltage-gated calcium channels.Nutrition & diabetes · 2024Article
- Cellular mechanisms of incretin hormone secretion.Journal of molecular endocrinology · 2024Review
- Nutrient Combinations Sensed by L-Cell Receptors Potentiate GLP-1 Secretion.International journal of molecular sciences · 2024Article
- Small intestinal CaSR-dependent and CaSR-independent protein sensing regulates feeding and glucose tolerance in rats.Nature metabolism · 2024Article
- Small intestinal protein sensing pathways regulate food intake and glucose homeostasis.Nature metabolism · 2024Article
- The intestine as an endocrine organ and the role of gut hormones in metabolic regulation.Nature reviews. Gastroenterology & hepatology · 2023Review
- G protein-coupled receptors: A target for microbial metabolites and a mechanistic link to microbiome-immune-brain interactions.Brain, behavior, & immunity - health · 2023Review
- Bioactive and Sensory Di- and Tripeptides Generated during Dry-Curing of Pork Meat.International journal of molecular sciences · 2023Review
- Pharmacological and Clinical Studies of Medicinal Plants That Inhibit Dipeptidyl Peptidase-IV.Drug design, development and therapy · 2023Review
- Enteroendocrine cell regulation of the gut-brain axis.Frontiers in neuroscience · 2023Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
aims/hypothesisIngested protein is a well-recognised stimulus for glucagon-like peptide-1 (GLP-1) release from intestinal L cells. This study aimed to characterise the molecular mechanisms employed by L cells to detect oligopeptides.
methodsGLP-1 secretion from murine primary colonic cultures and Ca(2+) dynamics in L cells were monitored in response to peptones and dipeptides. L cells were identified and purified based on their cell-specific expression of the fluorescent protein Venus, using GLU-Venus transgenic mice. Pharmacological tools and knockout mice were used to characterise candidate sensory pathways identified by expression analysis.
resultsGLP-1 secretion was triggered by peptones and di-/tripeptides, including the non-metabolisable glycine-sarcosine (Gly-Sar). Two sensory mechanisms involving peptide transporter-1 (PEPT1) and the calcium-sensing receptor (CaSR) were distinguishable. Responses to Gly-Sar (10 mmol/l) were abolished in the absence of extracellular Ca(2+) or by the L-type calcium-channel blocker nifedipine (10 μmol/l) and were PEPT1-dependent, as demonstrated by their sensitivity to pH and 4-aminomethylbenzoic acid and the finding of impaired responses in tissue from Pept1 (also known as Slc15a1) knockout mice. Peptone (5 mg/ml)-stimulated Ca(2+) responses were insensitive to nifedipine but were blocked by antagonists of CaSR. Peptone-stimulated GLP-1 secretion was not impaired in mice lacking the putative peptide-responsive receptor lysophosphatidic acid receptor 5 (LPAR5; also known as GPR92/93). CONCLUSIONS/
interpretationOligopeptides stimulate GLP-1 secretion through PEPT1-dependent electrogenic uptake and activation of CaSR. Both pathways are highly expressed in native L cells, and likely contribute to the ability of ingested protein to elevate plasma GLP-1 levels. Targeting nutrient-sensing pathways in L cells could be used to mobilise endogenous GLP-1 stores in humans, and could mimic some of the metabolic benefits of bariatric surgery.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.