ArticleAmerican journal of physiology. Endocrinology and metabolism2012
Glucagon-like peptide 2 induces vasoactive intestinal polypeptide expression in enteric neurons via phophatidylinositol 3-kinase-γ signaling.
Article in American journal of physiology. Endocrinology and metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 66 citations in OpenAlex.
- The Role of Vasoactive Intestinal Peptide in Glucagon-like Peptide-2-Mediated Intestinal Lipid Handling.International journal of molecular sciences · 2026Article
- Contribution of Vasoactive Intestinal Peptide to the Depressant Effects of Glucagon-like Peptide-2 on Neurally Induced Contractile Responses in Mouse Ileal Preparations.International journal of molecular sciences · 2025Article
- GLP-2 and GIP acutely increase superior mesenteric artery blood flow in male rats, and the effect is independent of nitric oxide and vasoactive intestinal peptide.Physiological reports · 2025Article
- TSLP links intestinal nutrient sensing with amplification of the ILC2-tuft cell circuit.Nature immunology · 2025Article
- 5-HTThe Journal of physiology · 2025Article
- Development of a Mechanism of Action-Reflective Cell-Based Reporter Gene Assay for Measuring Bioactivities of Therapeutic Glucagon-like Peptide-2 Analogues.Molecules (Basel, Switzerland) · 2025Article
- Ablation of PI3Kγ in neurons protects mice from diet-induced obesity MASLD and insulin resistance.iScience · 2025Article
- Intermittent fasting reduces inflammation and joint damage in a murine model of rheumatoid arthritis: insights from transcriptomic and metagenomic analyses.BMC rheumatology · 2024Article
- The Possible Involvement of Glucagon-like Peptide-2 in the Regulation of Food Intake through the Gut-Brain Axis.Nutrients · 2024Review
- GLP-2 regulation of intestinal lipid handling.Frontiers in physiology · 2024Review
- Computational Design of Potent and Selective d-Peptide Agonists of the Glucagon-like Peptide-2 Receptor.Journal of medicinal chemistry · 2023Article
- Article
- Glucagon-Like Peptide-2 Ameliorates Age-Associated Bone Loss and Gut Barrier Dysfunction in Senescence-Accelerated Mouse Prone 6 Mice.Gerontology · 2023Article
- The Enteric Glia and Its Modulation by the Endocannabinoid System, a New Target for Cannabinoid-Based Nutraceuticals?Molecules (Basel, Switzerland) · 2022Review
- Analysis of Intestinal Mucosa Integrity andAnimals : an open access journal from MDPI · 2021Article
- GLP-2 Prevents Neuronal and Glial Changes in the Distal Colon of Mice Chronically Treated with Cisplatin.International journal of molecular sciences · 2020Article
- Regulation of Chylomicron Secretion: Focus on Post-Assembly Mechanisms.Cellular and molecular gastroenterology and hepatology · 2019Review
- Neuropods.Cellular and molecular gastroenterology and hepatology · 2019Review
- Gut adaptation after metabolic surgery and its influences on the brain, liver and cancer.Nature reviews. Gastroenterology & hepatology · 2018Review
- Glucagon-Like Peptide-2 and the Enteric Nervous System Are Components of Cell-Cell Communication Pathway Regulating Intestinal NaFrontiers in nutrition · 2018Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Glucagon-like peptide 2 (GLP-2) is an enteroendocrine hormone trophic for intestinal mucosa; it has been shown to increase enteric neuronal expression of vasoactive intestinal polypeptide (VIP) in vivo. We hypothesized that GLP-2 would regulate VIP expression in enteric neurons via a phosphatidylinositol-3 kinase-γ (PI3Kγ) pathway. The mechanism of action of GLP-2 was investigated using primary cultures derived from the submucosal plexus (SMP) of the rat and mouse colon. GLP-2 (10(-8) M) stimulation for 24 h increased the proportion of enteric neurons expressing VIP (GLP-2: 40 ± 6% vs. control: 22 ± 5%). GLP-2 receptor expression was identified by immunohistochemistry on neurons (HuC/D+) and glial cells (GFAP+) but not on smooth muscle or fibroblasts in culture. Over 1-4 h, GLP-2 stimulation of SMP increased phosphorylated Akt/Akt ratios 6.1-fold, phosphorylated ERK/ERK 2.5-fold, and p70S6K 2.2-fold but did not affect intracellular cAMP. PI3Kγ gene deletion or pharmacological blockade of PI3Kγ, mammalian target of rapamycin (mTOR), and MEK/ERK pathways blocked the increase in VIP expression by GLP-2. GLP-2 increased the expression of growth factors and their receptors in SMP cells in culture [IGF-1r (3.2-fold increase), EGFr (5-fold), and ErbB-2-4r (6- to 7-fold)] and ligands [IGF-I (1.5-fold), amphiregulin (2.5-fold), epiregulin (3.2-fold), EGF (7.5-fold), heparin-bound EGF (2.0-fold), β-cellulin (50-fold increase), and neuregulins 2-4 (300-fold increase) (by qRT-PCR)]. We conclude that GLP-2 acts on enteric neurons and glial cells in culture via a PI3Kγ/Akt pathway, stimulating neuronal differentiation via mTOR and ERK pathways, and expression of receptors and ligands for the IGF-I and ErbB pathways.
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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.