Affinage

GCG

Pro-glucagon · UniProt P01275

Length
180 aa
Mass
20.9 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GCG encodes proglucagon, a precursor that is differentially processed in pancreatic alpha cells versus intestinal L cells and proglucagon-producing neurons to yield glucagon, GLP-1, and GLP-2; intestinal L cells secrete GLP-1 and GLP-2 separately in response to luminal nutrients, distinct from the co-secretion of a larger GLP-containing peptide with glucagon from pancreas (PMID:3530719, PMID:28884202). Segment-specific Gcg reduction establishes that distal-gut Gcg+ cells supply the GLP-1 evoked by GPR119, MC4R, TLR, and metformin stimulation, whereas proximal-gut cells supply nutrient-stimulated GLP-1 (PMID:32278655). The intestinotrophic product GLP-2 signals through the G protein-coupled GLP-2 receptor, which couples to adenylate cyclase and activates PKA-dependent transcriptional programs (AP-1, immediate-early genes) while engaging PKA-independent mitogenic mediators (PMID:10521425, PMID:10828489). GLP-2R is expressed not on the proliferating epithelium itself but on subepithelial myofibroblasts, enteric neurons, and enteroendocrine cells, so its trophic action proceeds through paracrine intermediates: KGF release from myofibroblasts drives colonic growth, and ErbB ligands (amphiregulin, epiregulin, HB-EGF) acting through EGFR/ErbB and intestinal IGF-1R mediate crypt cell proliferation (PMID:10982769, PMID:15544847, PMID:19523469, PMID:32147716). GLP-2 concurrently suppresses crypt cell apoptosis by inhibiting caspase-8/-3 activation and PARP cleavage and by upregulating Bcl-2 and IAP proteins, and it raises mesenteric blood flow via eNOS activation in VIP/NO enteric neurons (PMID:11212269, PMID:16401478, PMID:16954336). Beyond the gut, GLP-2R signaling regulates intestinal motility through cholinergic and nitrergic neurons (PMID:21752156), hepatic lipoprotein and bile acid homeostasis (PMID:29937214, PMID:30052880), bone resorption via a PTH-dependent parathyroid mechanism (PMID:33852173), and—through POMC neuron GLP-2R—suppresses food intake and gastric emptying via MC4R and enhances hepatic insulin sensitivity through a GLP-2R–p85α/PI3K–Akt–FoxO1 axis (PMID:22829581, PMID:23823479). The DPP-IV cleavage product GLP-2(3-33) acts as a partial agonist/competitive antagonist at the receptor (PMID:11738243).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1986 High

    Established that proglucagon products are processed and secreted differently by tissue, resolving how one gene yields distinct intestinal versus pancreatic peptides.

    Evidence RIA, HPLC on isolated perfused pig pancreas and ileum

    PMID:3530719

    Open questions at the time
    • Did not identify the processing enzymes responsible for tissue-specific cleavage
    • Functional roles of secreted GLP-1/GLP-2 not addressed
  2. 1984 Medium

    Localized the human GCG gene to a chromosomal locus, providing the genomic anchor for the proglucagon gene.

    Evidence Radioactive in situ hybridization to human metaphase chromosomes

    PMID:6546710

    Open questions at the time
    • Single method, single lab
    • No functional or regulatory information about the locus
  3. 1999 High

    Defined the GLP-2 receptor as a cAMP/PKA-coupled GPCR and showed that mitogenic signaling involves PKA-independent mediators, separating second-messenger generation from growth output.

    Evidence Transfected BHK cells expressing rat GLP-2R; cAMP, luciferase reporters, dominant-negative PKA, immunoblotting

    PMID:10521425

    Open questions at the time
    • Heterologous cell system, not native epithelium
    • Identity of PKA-independent mitogenic mediators undefined
  4. 2000 High

    Mapped GLP-2R expression to enteroendocrine cells, brain, and lung, raising the key insight that epithelial trophic effects must be indirect.

    Evidence Northern blot, RT-PCR, immunocytochemistry across rodent and human tissues; cloned receptor cAMP coupling

    PMID:10828489 PMID:10982769

    Open questions at the time
    • Did not identify which downstream mediators relay the signal to epithelium
    • Cell-type resolution limited at this stage
  5. 2001 High

    Showed GLP-2R activation is anti-apoptotic and that central GLP-2 suppresses feeding, expanding the receptor's role to cell survival and CNS energy balance.

    Evidence Caspase/PARP assays in transfected cells with murine chemotherapy models; ICV injection in WT and GLP-1R-/- mice with antagonist and reporter

    PMID:11212269 PMID:11262390

    Open questions at the time
    • Anti-apoptotic mechanism in transfected cells not yet linked to specific epithelial pathway
    • CNS GLP-2R-expressing neuronal populations not resolved
  6. 2002 High

    Characterized the DPP-IV product GLP-2(3-33) as a partial agonist/competitive antagonist, defining a built-in regulatory brake on GLP-2 signaling.

    Evidence Receptor binding and cAMP in human GLP-2R cells; in vivo co-administration intestinal growth assay

    PMID:11738243

    Open questions at the time
    • Physiological concentrations achieving antagonism in vivo unclear
    • No structural basis for partial agonism
  7. 2005 High

    Identified KGF from subepithelial myofibroblasts as an obligate paracrine mediator of colonic GLP-2 trophic action, providing the first molecular intermediate for indirect epithelial growth.

    Evidence IHC/ISH for GLP-2R on myofibroblasts; anti-KGF neutralization in vivo in mice

    PMID:15544847

    Open questions at the time
    • KGF dependence does not explain small intestinal growth
    • Other paracrine mediators not yet identified
  8. 2006 High

    Demonstrated that GLP-2 increases mesenteric blood flow via eNOS in enteric neurons and rapidly activates divergent pro-survival/pro-growth signaling in epithelium, connecting receptor activation to vascular and trophic physiology.

    Evidence qRT-PCR on LCM tissue, FISH, confocal triple immunostaining, blood flow measurement in neonatal pigs; in vivo GLP-2 infusion time-course in TPN-fed piglets

    PMID:16401478 PMID:16954336

    Open questions at the time
    • Epithelial signaling in piglets correlative as to which are GLP-2R-direct versus paracrine
    • Single species per study
  9. 2009 High

    Established ErbB ligand release and EGFR/ErbB signaling as required for GLP-2 proliferative and bowel-growth effects, and showed GLP-2 modulates VGCC in neurons, defining the dominant trophic effector and a neuronal action.

    Evidence Gene profiling and epistasis in WT, Glp2r-/-, Egfr(wa2) mice with pan-ErbB inhibitor; patch clamp and radioligand binding in hippocampal neurons

    PMID:19523469 PMID:19920220

    Open questions at the time
    • Mechanism linking GLP-2R to metalloproteinase-dependent ErbB ligand shedding incomplete
    • Physiological role of neuronal VGCC potentiation unclear
  10. 2011 Medium

    Resolved GLP-2R expression on excitatory and inhibitory enteric neurons and its inhibition of smooth muscle contractility, linking the receptor to gut motility control.

    Evidence IHC co-localization with neuronal markers; in vitro intestinal smooth muscle contractility with NO pathway pharmacology

    PMID:21752156

    Open questions at the time
    • ICC-DMP involvement inferred not demonstrated
    • Single lab, in vitro contractility only
  11. 2012 High

    Identified POMC neuron GLP-2R as the substrate for central anorectic and gastric-emptying effects and showed MC4R-dependence, mapping the CNS circuit for GLP-2 action.

    Evidence POMC-specific Glp2r conditional KO, ICV GLP-2, MC4R KO epistasis, gastric emptying breath test

    PMID:22829581

    Open questions at the time
    • Source of endogenous ligand reaching POMC neurons unclear
    • Link between POMC GLP-2R and downstream melanocortin release not detailed
  12. 2013 High

    Defined a GLP-2R–p85α/PI3K–Akt–FoxO1 axis in POMC neurons controlling hepatic glucose production, establishing a direct receptor–PI3K physical and functional link for central glucose regulation.

    Evidence POMC-specific Glp2r and p110α KO; Co-IP of GLP-2R–p85α; patch clamp; hyperinsulinemic-euglycemic clamp; FoxO1 fractionation

    PMID:23823479

    Open questions at the time
    • GLP-2R–p85α interaction shown by Co-IP without structural detail
    • Whether interaction is direct or scaffolded not resolved
  13. 2017 High

    Created a Gcg lineage-tracing tool that catalogued all proglucagon-producing cell types and their turnover, providing the cellular map underlying tissue-specific GCG biology.

    Evidence Gcg-CreERT2 knockin with tdTomato reporter, IHC marker analysis, plasma hormone measurement

    PMID:28884202

    Open questions at the time
    • Did not test functional consequences of cell turnover on peptide output
    • Bihormonal glucagon/PP cell function unexplored
  14. 2018 High

    Showed GLP-2R signaling governs hepatic lipoprotein metabolism and, in the Gcgr-/- background, controls bile acid levels and is required for small bowel growth while being dispensable for glucose homeostasis, distinguishing GLP-2R-dependent from -independent metabolic functions.

    Evidence VLDL/MTP assays and Glp2r-/- mice; double-KO mice (Gcgr-/-:Glp2r-/-, Gcgr-/-:Gpbar1-/-), VSG surgery, bile acid profiling

    PMID:29937214 PMID:30052880

    Open questions at the time
    • Tissue site of GLP-2R action on hepatic lipid not localized
    • Mechanism connecting GLP-2R to bile acid handling undefined
  15. 2020 High

    Pinpointed proximal versus distal Gcg+ cells as differential sources of secretagogue-specific GLP-1, and showed intestinal IGF-1R is required for GLP-2 proliferative but not trophic effects, refining both the source and effector arms of the pathway.

    Evidence Segment-specific Gcg knockdown mice with diverse secretagogues; IE-IGF-1R conditional KO and organoid reconstitution

    PMID:32147716 PMID:32278655

    Open questions at the time
    • How proliferative and trophic effects are mechanistically separated at the receptor level unclear
    • Relative contributions of EGF versus IGF-1 axes not quantified
  16. 2021 Medium

    Established that the GLP-2 antiresorptive bone effect is PTH-dependent via parathyroid GLP-2R, contrasting with the direct osteoblast/osteoclast action of GIP, defining an endocrine relay for skeletal regulation.

    Evidence Randomized crossover clinical study in hypoparathyroidism patients; bone turnover markers; receptor expression in human bone and parathyroid tissue

    PMID:33852173

    Open questions at the time
    • Single clinical study
    • Direct demonstration of parathyroid GLP-2R signaling causing PTH change not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The proteases and regulatory inputs that route proglucagon toward glucagon versus GLP-1/GLP-2 in different cell types, and the structural basis of GLP-2R coupling to its divergent paracrine and PI3K effectors, remain unresolved.
  • No timeline finding identifies the cell-specific proglucagon processing enzymes
  • No structural model of GLP-2R or its p85α interaction
  • Direct epithelial versus paracrine partitioning of GLP-2 effects incompletely quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005576 extracellular region 3
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1430728 Metabolism 2
Partners
GLP2R

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1986 GLP-1 and GLP-2 (predicted products of the proglucagon/GCG gene) are secreted separately from pig small intestine L cells (glicentin-producing cells) in parallel with intestinal glicentin upon luminal glucose or GRP stimulation, whereas pancreatic GCG expression yields a large peptide containing both GLP-1 and GLP-2 immunoreactivity co-secreted with glucagon upon arginine stimulation. RIA with specific antisera, reverse-phase HPLC, isolated perfused pig pancreas and ileum Endocrinology High 3530719
1999 GLP-2 signals through the GLP-2 receptor (a G protein-coupled receptor) to activate cAMP accumulation and PKA-dependent AP-1 transcriptional activity; it also stimulates c-fos, c-jun, junB and zif268 expression and transiently increases p70 S6 kinase, while inhibiting ERK1/2 and reducing serum-stimulated Elk-1 activity. Critically, 8-bromo-cAMP alone did not promote cell proliferation, indicating that GLP-2R mitogenic signaling involves PKA-independent downstream mediators. Transfected BHK cells expressing rat GLP-2R; cAMP assay, luciferase reporter assays, dominant-negative PKA inhibitor, immunoblotting The Journal of biological chemistry High 10521425
2000 GLP-2 receptor (GLP-2R) is expressed in enteroendocrine cells of the stomach, small bowel, and colon epithelium in humans and rodents, and also in the hypothalamus, brain stem, and lung, suggesting indirect epithelial action via downstream mediators. Northern blotting, RT-PCR, immunocytochemistry on rodent and human tissues Gastroenterology High 10982769
2001 GLP-2 receptor activation suppresses crypt cell apoptosis through inhibition of caspase-8 and caspase-3 activation and inhibition of PARP cleavage, as demonstrated in heterologous cells transfected with the GLP-2 receptor. Cells transfected with GLP-2 receptor; caspase-8/-3 activity assays, PARP cleavage by Western blot; murine chemotherapy models Cancer research Medium 11212269
2001 Central (intracerebroventricular) GLP-2 inhibits food intake in mice via GLP-2R expressed in multiple extrahypothalamic brain regions; disruption of GLP-1 receptor signaling (pharmacologically or genetically in GLP-1R-/- mice) potentiates the anorectic effect of GLP-2, indicating that GLP-1R signaling modulates CNS GLP-2 action. ICV injection in wild-type and GLP-1R-/- mice; exendin-(9-39) antagonist; LacZ transgenic reporter driven by GLP-2R promoter; GLP-2R expression mapping The Journal of biological chemistry High 11262390
2002 The primary DPP-IV degradation product GLP-2(3-33) binds the GLP-2 receptor with ~7.5% affinity of GLP-2(1-33), stimulates cAMP at ~15% efficacy, and acts as a partial agonist/competitive antagonist at the GLP-2 receptor, attenuating the intestinotrophic effects of GLP-2(1-33) when co-administered at high doses. Receptor-binding assay and cAMP accumulation in cells expressing transfected human GLP-2R; in vivo intestinal growth assay in mice with co-administration Regulatory peptides High 11738243
2005 GLP-2 stimulates colonic growth via keratinocyte growth factor (KGF) released from subepithelial myofibroblasts that express the GLP-2 receptor; anti-KGF antibody abolishes GLP-2-induced large intestinal growth but not small intestinal growth, establishing KGF as an obligate downstream paracrine mediator in the colon. Immunohistochemistry and in situ hybridization for GLP-2R on myofibroblasts; double-labeling for alpha-smooth muscle actin and KGF; in vivo GLP-2 ± KGF antibody infusion in mice Regulatory peptides High 15544847
2006 GLP-2R protein co-localizes with serotonin in enteroendocrine cells and with eNOS-expressing/VIP-positive enteric neurons in porcine intestine; GLP-2 infusion dose-dependently stimulates intestinal blood flow and upregulates intestinal eNOS mRNA, protein, and phosphorylation (eNOS-Ser1117), demonstrating that GLP-2 increases mesenteric blood flow via vasoactive neurotransmitters co-localized with GLP-2R. qRT-PCR on laser-capture microdissected subtissue, FISH, triple immunostaining/confocal microscopy; in vivo GLP-2 infusion in neonatal pigs with superior mesenteric artery blood flow measurement and eNOS quantification Gastroenterology High 16401478
2006 GLP-2 rapidly activates divergent intracellular signaling pathways in neonatal piglet intestinal epithelial cells: within 1–4 h, GLP-2 phosphorylates PKA, PKB/Akt, ERK1/2, CREB, and c-Fos, suppresses caspase-3 activation, and upregulates Bcl-2 and IAP family members (XIAP, cIAP-2), preceding the trophic morphological changes seen at 48 h. In vivo GLP-2 infusion in TPN-fed neonatal piglets with intestinal tissue analysis by Western blotting, immunostaining for signaling proteins; BrdU proliferation and TUNEL apoptosis assays at multiple time points American journal of physiology. Endocrinology and metabolism High 16954336
2009 ErbB receptor signaling is required for the proliferative and bowel-growth effects of GLP-2: exogenous GLP-2 rapidly induces amphiregulin, epiregulin, and HB-EGF (ErbB ligands) and immediate-early gene expression in the gut in a GLP-2R-dependent manner (absent in Glp2r-/- mice), and these effects and the stimulatory actions on crypt cell proliferation are abolished by the pan-ErbB inhibitor CI-1033 or markedly diminished in hypomorphic Egfr(wa2) mice. Gene expression profiling, GLP-2 administration in wild-type, Glp2r-/- and Egfr(wa2) mice; pan-ErbB inhibitor CI-1033; metalloproteinase inhibitor; crypt cell proliferation assay Gastroenterology High 19523469
2009 GLP-2 potentiates L-type voltage-gated Ca2+ channel (VGCC) activity in hippocampal neurons through a PKA-dependent mechanism, and this potentiation partially mediates GLP-2-stimulated glucose uptake by primary hippocampal neurons. GLP-2(1-33) binds specifically to hippocampal neurons with Kd = 0.48 nM. Whole-cell patch clamp recording of barium currents; PKA inhibitor (PKI(14-22)); nifedipine for L-type Ca2+ channel block; [3H]-2-deoxyglucose uptake; 125I-labeled GLP-2 binding; fluorescent glucose analog imaging American journal of physiology. Endocrinology and metabolism High 19920220
2012 GLP-2R in POMC neurons suppresses food intake and gastric emptying; GLP-2-mediated anorectic and motility effects require MC4R signaling, as these effects were abolished in MC4R KO mice. Mice lacking Glp2r specifically in POMC neurons showed hyperphagia, accelerated gastric emptying, and late-onset obesity. Cre-LoxP conditional knockout (POMC-specific Glp2r deletion); ICV GLP-2 infusion; MC4R KO mice; 13C-octanoic acid breath test for gastric emptying; food intake measurement American journal of physiology. Endocrinology and metabolism High 22829581
2013 Central GLP-2 enhances hepatic insulin sensitivity through PI3K signaling in POMC neurons: GLP-2R activation in POMC neurons initiates GLP-2R–p85α interaction, facilitating PI3K–Akt-dependent FoxO1 nuclear exclusion, modulating membrane excitability, and suppressing hepatic glucose production (HGP). Mice lacking GLP-2R in POMC neurons show glucose intolerance and hepatic insulin resistance. Conditional knockout (POMC-specific Glp2r-/- and POMC-p110α KO); Co-IP (GLP-2R–p85α); patch clamp for POMC neuron excitability; hyperinsulinemic-euglycemic clamp; FoxO1 nuclear/cytoplasmic fractionation; gluconeogenesis assay Cell metabolism High 23823479
2011 GLP-2R is expressed on both excitatory (substance P/ChAT-positive) and inhibitory (VIP/nNOS-positive) myenteric and submucosal neurons in mouse duodenum; GLP-2 inhibits smooth muscle contractility by decreasing cholinergic neurotransmission and increasing nitric oxide production, likely via ICC-DMP recruitment. Immunohistochemistry for GLP-2R co-localization with neuronal markers; in vitro contractility assay of intestinal smooth muscle; nitric oxide pathway pharmacology Neurogastroenterology and motility Medium 21752156
2018 GLP-2R signaling controls circulating bile acid levels and relative bile acid species proportions in Gcgr-/- mice (loss of Glp2r in Gcgr-/- background lowers bile acids), and is required for small bowel growth in Gcgr-/- mice; however, GLP-2R is dispensable for glucose homeostasis in Gcgr-/- mice and for metabolic improvements after vertical sleeve gastrectomy. Double-knockout mice (Gcgr-/-:Glp2r-/-; Gcgr-/-:Gpbar1-/-); Glp2r-/- mice + VSG surgery; bile acid profiling; glucose tolerance testing; intestinal mass measurement Molecular metabolism High 29937214
2020 Distal gut Gcg+ endocrine cells are the primary source of GLP-1 secreted in response to GPR119 agonism (AR231453), MC4R agonism (LY2112688), and LPS/TLR activation, as well as the acute GLP-1 response to metformin; in contrast, proximal gut Gcg+ cells are the main source for nutrient-stimulated (olive oil, arginine) GLP-1 secretion. Intestine-selective Gcg knockdown mice (GcgGut-/- and GcgDistalGut-/-); plasma GLP-1 measurement after administration of diverse secretagogues; glucose measurement Molecular metabolism High 32278655
2020 The proliferative effects of GLP-2 in the intestine are partially dependent on the intestinal epithelial IGF-1 receptor (IE-IGF-1R): IE-IGF-1R KO mice show diminished crypt cell proliferative responses to GLP-2 alone or with EGF, while small intestinal weight and crypt-villus height increases are preserved, indicating that GLP-2 acts through EGF and IGF-1R pathways for its proliferative but not its trophic effects. IE-IGF-1R conditional KO mice treated with GLP-2 and/or EGF; intestinal organoid cultures with EGF/IGF-1 treatment; intestinal growth parameter measurement; crypt cell proliferation assay Endocrinology High 32147716
1984 The human glucagon gene (GCG) was mapped to chromosome segment 2q36–37 by in situ hybridization using a 3H-labeled bovine glucagon cDNA probe. Radioactive in situ hybridization to human metaphase chromosomes Cytogenetics and cell genetics Medium 6546710
2017 A Gcg CreERT2 knockin mouse was generated by inserting CreERT2 into the endogenous Gcg locus; tamoxifen-induced recombination labeled 94–97% of pancreatic alpha cells, all known proglucagon-producing cell types (L cells, GLP-1-producing neurons), and revealed a glucagon/PP bihormonal cell population (~14–25% of PP+ cells). Intestinal L cells undergo rapid turnover (~half replaced within 2 weeks), whereas alpha cells and GLP-1 neurons persist for ≥5 months post-tamoxifen. Homologous recombination knockin; Cre-LoxP with Rosa26-tdTomato reporter; immunohistochemistry for cell-type markers; plasma glucagon, GLP-1 measurement Diabetologia High 28884202
2018 GLP-2 dysregulates hepatic lipoprotein metabolism: exogenous GLP-2 administration increases fasting dyslipidemia, hepatic VLDL production, de novo lipogenesis gene expression, and hepatic lipid accumulation in hamsters and mice. Conversely, Glp2r-/- mice show reduced VLDL secretion and microsomal transfer protein activity with exacerbated hepatic lipid accumulation, indicating that GLP-2R signaling is required for normal hepatic lipid/lipoprotein homeostasis. IP GLP-2 administration in hamsters and C57BL/6J mice; Glp2r-/- mice on HFD; VLDL production assay; hepatic gene expression (lipogenesis genes); MTP lipid transfer activity; liver lipid quantification Endocrinology High 30052880
2021 The GLP-2 antiresorptive effect on bone depends on PTH and is likely mediated through GLP-2R expressed in the parathyroid gland, whereas GIP acts directly on bone via GIPR expressed in osteoblasts and osteoclasts independent of PTH. GLP-2R was absent or only weakly expressed in osteoclasts. Randomized crossover clinical study in hypoparathyroidism patients; subcutaneous GIP and GLP-2 injections; bone turnover markers; GLP-2R and GIPR expression in human osteoblasts, osteoclasts, and parathyroid tissue Journal of bone and mineral research Medium 33852173
2000 GLP-2R activation is coupled to increased adenylate cyclase activity; the GLP-2R is expressed in a highly tissue-specific manner predominantly in the gastrointestinal tract (as established by studies of the cloned GLP-2 receptor). Cloned GLP-2R expressed in heterologous cells; adenylate cyclase/cAMP assay; tissue-specific expression analysis Regulatory peptides Medium 10828489

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy. Nature genetics 627 9462747
1986 Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separately from pig small intestine but not pancreas. Endocrinology 444 3530719
2000 Enteroendocrine localization of GLP-2 receptor expression in humans and rodents. Gastroenterology 283 10982769
2006 GLP-2 receptor localizes to enteric neurons and endocrine cells expressing vasoactive peptides and mediates increased blood flow. Gastroenterology 220 16401478
1998 GLP-2 augments the adaptive response to massive intestinal resection in rat. The American journal of physiology 189 9815019
1982 Molecular structure of r(GCG)d(TATACGC): a DNA--RNA hybrid helix joined to double helical DNA. Nature 185 6181416
2005 GLP-2 stimulates colonic growth via KGF, released by subepithelial myofibroblasts with GLP-2 receptors. Regulatory peptides 179 15544847
2013 The gut microbiota reduces leptin sensitivity and the expression of the obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived neurotrophic factor (Bdnf) in the central nervous system. Endocrinology 168 23892476
2000 GLP-2 stimulates intestinal growth in premature TPN-fed pigs by suppressing proteolysis and apoptosis. American journal of physiology. Gastrointestinal and liver physiology 156 11093948
1999 Human [Gly2]GLP-2 reduces the severity of colonic injury in a murine model of experimental colitis. The American journal of physiology 151 9886982
2021 Effects on weight loss and glycemic control with SAR441255, a potent unimolecular peptide GLP-1/GIP/GCG receptor triagonist. Cell metabolism 145 34932984
2002 Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors. Receptors & channels 140 12529935
2009 A triplet repeat expansion genetic mouse model of infantile spasms syndrome, Arx(GCG)10+7, with interneuronopathy, spasms in infancy, persistent seizures, and adult cognitive and behavioral impairment. The Journal of neuroscience : the official journal of the Society for Neuroscience 138 19587282
1987 Radio-immunoassays for glucagon-like peptides 1 and 2 (GLP-1 and GLP-2). Scandinavian journal of clinical and laboratory investigation 137 3576119
2001 Glucagon-like peptide (GLP)-2 reduces chemotherapy-associated mortality and enhances cell survival in cells expressing a transfected GLP-2 receptor. Cancer research 127 11212269
2010 Preproglucagon derived peptides GLP-1, GLP-2 and oxyntomodulin in the CNS: role of peripherally secreted and centrally produced peptides. Progress in neurobiology 119 20638440
1981 Base-pair substitution hotspots in GAG and GCG nucleotide sequences in Escherichia coli K-12 induced by cis-diamminedichloroplatinum (II). Proceedings of the National Academy of Sciences of the United States of America 111 7031665
2021 GCG inhibits SARS-CoV-2 replication by disrupting the liquid phase condensation of its nucleocapsid protein. Nature communications 104 33837182
2004 Nutrient-stimulated GLP-2 release and crypt cell proliferation in experimental short bowel syndrome. American journal of physiology. Gastrointestinal and liver physiology 101 15388486
2001 Glucagon-like peptide (GLP)-2 action in the murine central nervous system is enhanced by elimination of GLP-1 receptor signaling. The Journal of biological chemistry 99 11262390
1986 Raman spectra of single crystals of r(GCG)d(CGC) and d(CCCCGGGG) as models for A DNA, their structure transitions in aqueous solution, and comparison with double-helical poly(dG).poly(dC). Biochemistry 90 3954991
2009 ErbB signaling is required for the proliferative actions of GLP-2 in the murine gut. Gastroenterology 88 19523469
1999 Identification of glucagon-like peptide-2 (GLP-2)-activated signaling pathways in baby hamster kidney fibroblasts expressing the rat GLP-2 receptor. The Journal of biological chemistry 88 10521425
2013 Central GLP-2 enhances hepatic insulin sensitivity via activating PI3K signaling in POMC neurons. Cell metabolism 86 23823479
2001 GLP-2 has differential effects on small intestine growth and function in fetal and neonatal pigs. American journal of physiology. Regulatory, integrative and comparative physiology 83 11705785
2002 Role of luminal nutrients and endogenous GLP-2 in intestinal adaptation to mid-small bowel resection. American journal of physiology. Gastrointestinal and liver physiology 77 12505881
2004 Teduglutide ([Gly2]GLP-2) protects small intestinal stem cells from radiation damage. Cell proliferation 75 15548172
2002 The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist. Regulatory peptides 75 11738243
2012 GLP-2 receptor in POMC neurons suppresses feeding behavior and gastric motility. American journal of physiology. Endocrinology and metabolism 67 22829581
2018 A novel GLP-1/GIP/Gcg triagonist reduces cognitive deficits and pathology in the 3xTg mouse model of Alzheimer's disease. Hippocampus 59 29473979
2020 Intestine-selective reduction of Gcg expression reveals the importance of the distal gut for GLP-1 secretion. Molecular metabolism 58 32278655
2003 Introduction of enteral food increases plasma GLP-2 and decreases GLP-2 receptor mRNA abundance during pig development. The Journal of nutrition 57 12771317
2016 GLP2: an underestimated signal for improving glycaemic control and insulin sensitivity. The Journal of endocrinology 52 27048234
2004 GLP-2 levels in infants with intestinal dysfunction. Pediatric research 52 15201402
2012 GLP2-2G-XTEN: a pharmaceutical protein with improved serum half-life and efficacy in a rat Crohn's disease model. PloS one 50 23189208
2004 Comparative effects of glucagon-like peptide-2 (GLP-2), growth hormone (GH), and keratinocyte growth factor (KGF) on markers of gut adaptation after massive small bowel resection in rats. JPEN. Journal of parenteral and enteral nutrition 50 15568286
2000 New frontiers in the biology of GLP-2. Regulatory peptides 50 10828489
2013 Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated type 2 diabetic rats. The Journal of endocrinology 49 23757509
1992 Conformation of guanine-8-oxoadenine base pairs in the crystal structure of d(CGCGAATT(O8A)GCG). Biochemistry 49 1390625
1983 Proton NMR studies on the covalently linked RNA-DNA hybrid r(GCG)d(TATACGC). Assignment of proton resonances by application of the nuclear Overhauser effect. Nucleic acids research 49 6193486
1983 Specifically alkylated DNA fragments. Synthesis and physical characterization of d[CGC(O6Me)GCG] and d[CGT(O6Me)GCG]. Nucleic acids research 49 6856460
2006 GLP-2 rapidly activates divergent intracellular signaling pathways involved in intestinal cell survival and proliferation in neonatal piglets. American journal of physiology. Endocrinology and metabolism 48 16954336
2006 DPPIV inhibitors extend GLP-2 mediated tumour promoting effects on intestinal cancer cells. Regulatory peptides 46 16908079
2003 Effect of GLP-2 on mucosal morphology and SGLT1 expression in tissue-engineered neointestine. American journal of physiology. Gastrointestinal and liver physiology 45 12919941
2000 GCG genetic expansions in Italian patients with oculopharyngeal muscular dystrophy. Neurology 45 10680791
2012 GLP-2 enhances barrier formation and attenuates TNFα-induced changes in a Caco-2 cell model of the intestinal barrier. Regulatory peptides 44 22809889
2014 GLP-2 suppresses LPS-induced inflammation in macrophages by inhibiting ERK phosphorylation and NF-κB activation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 43 25116357
1998 W2H: WWW interface to the GCG sequence analysis package. Bioinformatics (Oxford, England) 43 9682058
2004 Increased expression of specific intestinal amino acid and peptide transporter mRNA in rats fed by TPN is reversed by GLP-2. The Journal of nutrition 42 15514259
2000 Oculopharyngeal MD among Bukhara Jews is due to a founder (GCG)9 mutation in the PABP2 gene. Neurology 42 11087766
2008 Exogenous glucagon-like peptide-2 (GLP-2) augments GLP-2 receptor mRNA and maintains proglucagon mRNA levels in resected rats. JPEN. Journal of parenteral and enteral nutrition 41 18443137
2015 GLP-2 as Beneficial Factor in the Glucose Homeostasis in Mice Fed a High Fat Diet. Journal of cellular physiology 40 25967277
2011 GLP-2 receptor expression in excitatory and inhibitory enteric neurons and its role in mouse duodenum contractility. Neurogastroenterology and motility 40 21752156
2008 GCG-rich tea catechins are effective in lowering cholesterol and triglyceride concentrations in hyperlipidemic rats. Lipids 40 18365267
2019 The Discovery of GLP-2 and Development of Teduglutide for Short Bowel Syndrome. ACS pharmacology & translational science 39 32219218
2022 GIP and GLP-2 together improve bone turnover in humans supporting GIPR-GLP-2R co-agonists as future osteoporosis treatment. Pharmacological research 37 34995796
2018 GLP-2 analog teduglutide significantly reduces need for parenteral nutrition and stool frequency in a real-life setting. Therapeutic advances in gastroenterology 37 30364471
2014 GLP-2: what do we know? What are we going to discover? Regulatory peptides 37 25218018
2010 Gcg-XTEN: an improved glucagon capable of preventing hypoglycemia without increasing baseline blood glucose. PloS one 37 20418955
2005 Transgenic expression of an expanded (GCG)13 repeat PABPN1 leads to weakness and coordination defects in mice. Neurobiology of disease 37 15755680
1994 The solution structure of the r(gcg)d(TATACCC):d(GGGTATACGC) Okazaki fragment contains two distinct duplex morphologies connected by a junction. Journal of molecular biology 37 8064857
2014 A tetrahelical DNA fold adopted by tandem repeats of alternating GGG and GCG tracts. Nature communications 36 25500730
2017 Gcg CreERT2 knockin mice as a tool for genetic manipulation in pancreatic alpha cells. Diabetologia 35 28884202
2020 Anti-melanogenic effects of epigallocatechin-3-gallate (EGCG), epicatechin-3-gallate (ECG) and gallocatechin-3-gallate (GCG) via down-regulation of cAMP/CREB /MITF signaling pathway in B16F10 melanoma cells. Fitoterapia 34 32454171
1984 Localization of the human glucagon gene (GCG) to chromosome segment 2q36----37. Cytogenetics and cell genetics 34 6546710
2004 Plasma GLP-2 levels and intestinal markers in the juvenile pig during intestinal adaptation: effects of different diet regimens. Digestive diseases and sciences 33 15573929
2020 A GLP-1/GIP/Gcg receptor triagonist improves memory behavior, as well as synaptic transmission, neuronal excitability and Ca2+ homeostasis in 3xTg-AD mice. Neuropharmacology 32 32147454
2002 Association between the GCG polymorphism of the selenium dependent GPX1 gene and the risk of young onset prostate cancer. Prostate cancer and prostatic diseases 32 12496980
2021 The Antiresorptive Effect of GIP, But Not GLP-2, Is Preserved in Patients With Hypoparathyroidism-A Randomized Crossover Study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 31 33852173
2017 Interdependency of EGF and GLP-2 Signaling in Attenuating Mucosal Atrophy in a Mouse Model of Parenteral Nutrition. Cellular and molecular gastroenterology and hepatology 31 28462383
2004 Glucagon-like peptide 2 (GLP-2), an intestinotrophic mediator. Current protein & peptide science 31 14965320
2020 Dipeptidyl peptidase 4 inhibitor sitagliptin protected against dextran sulfate sodium-induced experimental colitis by potentiating the action of GLP-2. Acta pharmacologica Sinica 30 32398684
1994 Guanine-1,N6-ethenoadenine base pairs in the crystal structure of d(CGCGAATT(epsilon dA)GCG). Biochemistry 30 8161534
2021 Dapiglutide, a novel dual GLP-1 and GLP-2 receptor agonist, attenuates intestinal insufficiency in a murine model of short bowel. JPEN. Journal of parenteral and enteral nutrition 29 34705281
2019 Increased Body Weight and Fat Mass After Subchronic GIP Receptor Antagonist, but Not GLP-2 Receptor Antagonist, Administration in Rats. Frontiers in endocrinology 29 31447774
2016 Synthesis and Pharmacological Characterization of Novel Glucagon-like Peptide-2 (GLP-2) Analogues with Low Systemic Clearance. Journal of medicinal chemistry 28 26986178
2004 Patient interleukin-18 GCG haplotype associates with improved survival and decreased transplant-related mortality after unrelated-donor bone marrow transplantation. British journal of haematology 27 15327523
2001 GCG repeats and phenotype in oculopharyngeal muscular dystrophy. Muscle & nerve 27 11150975
2000 Oculopharyngeal muscular dystrophy in a Japanese family with a short GCG expansion (GCG)(11) in PABP2 gene. Neuromuscular disorders : NMD 27 10734263
2020 GLP-2, EGF, and the Intestinal Epithelial IGF-1 Receptor Interactions in the Regulation of Crypt Cell Proliferation. Endocrinology 24 32147716
2019 GC-(4→8)-GCG, A Proanthocyanidin Dimer from Camellia ptilophylla, Modulates Obesity and Adipose Tissue Inflammation in High-Fat Diet Induced Obese Mice. Molecular nutrition & food research 24 30893514
2010 Expression of mRNA for proglucagon and glucagon-like peptide-2 (GLP-2) receptor in the ruminant gastrointestinal tract and the influence of energy intake. Domestic animal endocrinology 24 20688461
2023 EGCG, GCG, TFDG, or TSA Inhibiting Melanin Synthesis by Downregulating MC1R Expression. International journal of molecular sciences 23 37446194
2018 GLP-2 receptor signaling controls circulating bile acid levels but not glucose homeostasis in Gcgr-/- mice and is dispensable for the metabolic benefits ensuing after vertical sleeve gastrectomy. Molecular metabolism 23 29937214
2017 New Peptide Inhibitor of Dipeptidyl Peptidase IV, EMDB-1 Extends the Half-Life of GLP-2 and Attenuates Colitis in Mice after Topical Administration. The Journal of pharmacology and experimental therapeutics 23 28724693
2010 The intestinotrophic peptide, GLP-2, counteracts the gastrointestinal atrophy in mice induced by the epidermal growth factor receptor inhibitor, erlotinib, and cisplatin. Digestive diseases and sciences 23 20112065
2009 GLP-2 potentiates L-type Ca2+ channel activity associated with stimulated glucose uptake in hippocampal neurons. American journal of physiology. Endocrinology and metabolism 23 19920220
1993 Simultaneous incorporations of two anticancer drugs into DNA. The structures of formaldehyde-cross-linked adducts of daunorubicin-d(CG(araC)GCG) and doxorubicin-d(CA(araC)GTG) complexes at high resolution. The Journal of biological chemistry 23 8486678
2019 Neurotrophic and neuroprotective effects of a monomeric GLP-1/GIP/Gcg receptor triagonist in cellular and rodent models of mild traumatic brain injury. Experimental neurology 22 31730763
2017 FFA3 Activation Stimulates Duodenal Bicarbonate Secretion and Prevents NSAID-Induced Enteropathy via the GLP-2 Pathway in Rats. Digestive diseases and sciences 22 28523577
2017 Differential expression of glucagon-like peptide-2 (GLP-2) is involved in pancreatic islet cell adaptations to stress and beta-cell survival. Peptides 22 28746825
2010 GLP-2 receptor agonism ameliorates inflammation and gastrointestinal stasis in murine postoperative ileus. The Journal of pharmacology and experimental therapeutics 22 20167840
2022 A GLP-1/glucagon (GCG)/CCK2 receptors tri-agonist provides new therapy for obesity and diabetes. British journal of pharmacology 21 35484823
2020 GLP-2 Acutely Prevents Endotoxin-Related Increased Intestinal Paracellular Permeability in Rats. Digestive diseases and sciences 21 32006214
2020 The GLP-2 analogue elsiglutide reduces diarrhoea caused by the tyrosine kinase inhibitor lapatinib in rats. Cancer chemotherapy and pharmacology 21 32060615
2018 GLP-2 Dysregulates Hepatic Lipoprotein Metabolism, Inducing Fatty Liver and VLDL Overproduction in Male Hamsters and Mice. Endocrinology 21 30052880
2000 New developments in the biology of the glucagon-like peptides GLP-1 and GLP-2. Annals of the New York Academy of Sciences 21 11193827
2022 Therapeutic Potential of GLP-2 Analogs in Gastrointestinal Disorders: Current Knowledge, Nutritional Aspects, and Future Perspectives. Current nutrition reports 20 35933503
2020 APC mutations in human colon lead to decreased neuroendocrine maturation of ALDH+ stem cells that alters GLP-2 and SST feedback signaling: Clue to a link between WNT and retinoic acid signalling in colon cancer development. PloS one 20 33112876
2019 A dual GLP-1 and Gcg receptor agonist rescues spatial memory and synaptic plasticity in APP/PS1 transgenic mice. Hormones and behavior 20 31765661

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