Gene Symbol: gcga
Description: glucagon a
Alias: gcg, glu, zgc:103616, glucagon, GLP-1
Species: zebrafish

Top Publications

  1. Argenton F, Zecchin E, Bortolussi M. Early appearance of pancreatic hormone-expressing cells in the zebrafish embryo. Mech Dev. 1999;87:217-21 pubmed
    Adult pancreatic islets comprise four cell types, alpha, beta, delta and PP, expressing glucagon, insulin, somatostatin and pancreatic-polypeptide, respectively, arising from cell lineages whose relationships during endocrine pancreas ..
  2. Yee N, Yusuff S, Pack M. Zebrafish pdx1 morphant displays defects in pancreas development and digestive organ chirality, and potentially identifies a multipotent pancreas progenitor cell. Genesis. 2001;30:137-40 pubmed
  3. Pauls S, Zecchin E, Tiso N, Bortolussi M, Argenton F. Function and regulation of zebrafish nkx2.2a during development of pancreatic islet and ducts. Dev Biol. 2007;304:875-90 pubmed
    ..2a in the development of the pancreatic ducts. ..
  4. Dalgin G, Ward A, Hao L, Beattie C, Nechiporuk A, Prince V. Zebrafish mnx1 controls cell fate choice in the developing endocrine pancreas. Development. 2011;138:4597-608 pubmed publisher
    ..cell types ultimately arise, including the insulin-producing beta cells and the antagonistically acting glucagon-producing alpha cells...
  5. Moro E, Gnügge L, Braghetta P, Bortolussi M, Argenton F. Analysis of beta cell proliferation dynamics in zebrafish. Dev Biol. 2009;332:299-308 pubmed publisher
  6. diIorio P, Moss J, Sbrogna J, Karlstrom R, Moss L. Sonic hedgehog is required early in pancreatic islet development. Dev Biol. 2002;244:75-84 pubmed
    ..The early action of Shh may be part of a more general process allowing neuroendocrine cells to originate in nonneuroectodermally derived tissues. ..
  7. Binot A, Manfroid I, Flasse L, Winandy M, Motte P, Martial J, et al. Nkx6.1 and nkx6.2 regulate alpha- and beta-cell formation in zebrafish by acting on pancreatic endocrine progenitor cells. Dev Biol. 2010;340:397-407 pubmed publisher
    ..On the basis of our data, we propose a model in which nkx6.1 and nkx6.2, by allowing the establishment of the endocrine progenitor pool, control alpha- and beta-cell differentiation. ..
  8. Chen Y, Lu Y, Li I, Hwang S. Zebrafish Agr2 is required for terminal differentiation of intestinal goblet cells. PLoS ONE. 2012;7:e34408 pubmed publisher
    ..However, whether increased endoplasmic reticulum (ER) stress occurs in Agr2(-/-) mice remains a controversial issue...
  9. Mavropoulos A, Devos N, Biemar F, Zecchin E, Argenton F, Edlund H, et al. sox4b is a key player of pancreatic alpha cell differentiation in zebrafish. Dev Biol. 2005;285:211-23 pubmed
    ..In addition, sox4b knock-down leads to a drastic reduction in glucagon expression, while other pancreatic markers including insulin, somatostatin, and trypsin are not significantly ..

More Information


  1. Kim H, Schleiffarth J, Jessurun J, Sumanas S, Petryk A, Lin S, et al. Wnt5 signaling in vertebrate pancreas development. BMC Biol. 2005;3:23 pubmed
    ..This study opens the door for further investigation into a role of Wnt signaling in vertebrate organ development and disease. ..
  2. Zecchin E, Filippi A, Biemar F, Tiso N, Pauls S, Ellertsdottir E, et al. Distinct delta and jagged genes control sequential segregation of pancreatic cell types from precursor pools in zebrafish. Dev Biol. 2007;301:192-204 pubmed
    ..Beta-cells producing insulin, alpha-cells producing glucagon, and exocrine cells secreting digestive enzymes differentiate sequentially from a common primordium...
  3. Stafford D, Prince V. Retinoic acid signaling is required for a critical early step in zebrafish pancreatic development. Curr Biol. 2002;12:1215-20 pubmed
    ..In addition to being required for pancreatic specification, RA has the capacity to transfate anterior endoderm to a pancreatic fate. ..
  4. Delporte F, Pasque V, Devos N, Manfroid I, Voz M, Motte P, et al. Expression of zebrafish pax6b in pancreas is regulated by two enhancers containing highly conserved cis-elements bound by PDX1, PBX and PREP factors. BMC Dev Biol. 2008;8:53 pubmed publisher
    ..This study also provides a striking example of how adaptative evolution of gene regulatory sequences upon gene duplication progressively leads to subfunctionalization of the paralogous gene pair. ..
  5. Wan H, Korzh S, Li Z, Mudumana S, Korzh V, Jiang Y, et al. Analyses of pancreas development by generation of gfp transgenic zebrafish using an exocrine pancreas-specific elastaseA gene promoter. Exp Cell Res. 2006;312:1526-39 pubmed
    ..Thus, our works demonstrated the new transgenic line provided a useful experimental tool in analyzing exocrine pancreas development...
  6. Verbruggen V, Ek O, Georlette D, Delporte F, Von Berg V, Detry N, et al. The Pax6b homeodomain is dispensable for pancreatic endocrine cell differentiation in zebrafish. J Biol Chem. 2010;285:13863-73 pubmed publisher
    ..embryos performed by injection of small amounts of pax6b morpholinos caused a clear rise in alpha cell number and in glucagon expression, emphasizing the importance of the fine tuning of the Pax6b level to its biological activity.
  7. Kim H, Sumanas S, Palencia Desai S, Dong Y, Chen J, Lin S. Genetic analysis of early endocrine pancreas formation in zebrafish. Mol Endocrinol. 2006;20:194-203 pubmed
    ..These mutations affect different processes in pancreatic islet development. Additional analysis on glucagon and somatostatin cell specification revealed that somatostatin cells are specified at a separate domain from ..
  8. Biemar F, Argenton F, Schmidtke R, Epperlein S, Peers B, Driever W. Pancreas development in zebrafish: early dispersed appearance of endocrine hormone expressing cells and their convergence to form the definitive islet. Dev Biol. 2001;230:189-203 pubmed
    ..M. Milewski et al., 1998, Endocrinology 139, 1440-1449), glucagon, somatostatin (F. Argenton et al., 1999, Mech. Dev. 87, 217-221), islet-1 (Korzh et al...
  9. Timme Laragy A, Sant K, Rousseau M, diIorio P. Deviant development of pancreatic beta cells from embryonic exposure to PCB-126 in zebrafish. Comp Biochem Physiol C Toxicol Pharmacol. 2015;178:25-32 pubmed publisher
    ..We measured gene expression of preproinsulin a, somatostatin2, pdx1, ghrelin, and glucagon. Expression of preproinsulin a increased with PCB treatment in wildtype embryos, while expression of all measured ..
  10. Kloosterman W, Lagendijk A, Ketting R, Moulton J, Plasterk R. Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development. PLoS Biol. 2007;5:e203 pubmed
    ..The miRNA knockdown strategy presented here will be widely used to unravel miRNA function in zebrafish. ..
  11. Kinkel M, Eames S, Alonzo M, Prince V. Cdx4 is required in the endoderm to localize the pancreas and limit beta-cell number. Development. 2008;135:919-29 pubmed publisher
    ..In support of this, we demonstrate that in cdx4-deficient embryos treated with RA, ectopic beta-cells are located well posterior to the normal pancreatic domain. ..
  12. Musson M, Jepeal L, Finnerty J, Wolfe M. Evolutionary expression of glucose-dependent-insulinotropic polypeptide (GIP). Regul Pept. 2011;171:26-34 pubmed publisher
    ..Phylogenetic analysis of the glucagon-like ligands suggested proglucagon as the common ancestor, supporting the theory that GIP arose as a gene ..
  13. Sant K, Jacobs H, Borofski K, Moss J, Timme Laragy A. Embryonic exposures to perfluorooctanesulfonic acid (PFOS) disrupt pancreatic organogenesis in the zebrafish, Danio rerio. Environ Pollut. 2017;220:807-817 pubmed publisher
  14. Musson M, Jepeal L, Mabray P, Zhdanova I, Cardoso W, Wolfe M. Expression of glucose-dependent insulinotropic polypeptide in the zebrafish. Am J Physiol Regul Integr Comp Physiol. 2009;297:R1803-12 pubmed publisher
    ..Although previous studies have identified four receptors with glucagon receptor-like sequences in the zebrafish, one of which possesses the capacity to bind GIP, a functional analysis ..
  15. Wilfinger A, Arkhipova V, Meyer D. Cell type and tissue specific function of islet genes in zebrafish pancreas development. Dev Biol. 2013;378:25-37 pubmed publisher
    ..In isl1 mutants, early forming first wave cells show virtually no glucagon expression and a reduced number of cells expressing insulin and somatostatin, while in the later born second wave ..
  16. Kinkel M, Sefton E, Kikuchi Y, Mizoguchi T, Ward A, Prince V. Cyp26 enzymes function in endoderm to regulate pancreatic field size. Proc Natl Acad Sci U S A. 2009;106:7864-9 pubmed publisher
    ..Such feedback can maintain consistent levels of RA signaling, despite environmental fluctuations in RA concentration, thus ensuring a consistent size and location of the pancreatic field. ..
  17. Oren D, Wei Y, Skrabanek L, Chow B, Mommsen T, Mojsov S. Structural Mapping and Functional Characterization of Zebrafish Class B G-Protein Coupled Receptor (GPCR) with Dual Ligand Selectivity towards GLP-1 and Glucagon. PLoS ONE. 2016;11:e0167718 pubmed publisher
    GLP-1 and glucagon regulate glucose metabolism through a network of metabolic pathways initiated upon binding to their specific receptors that belong to class B G-protein coupled receptors (GPCRs)...
  18. Zecchin E, Mavropoulos A, Devos N, Filippi A, Tiso N, Meyer D, et al. Evolutionary conserved role of ptf1a in the specification of exocrine pancreatic fates. Dev Biol. 2004;268:174-84 pubmed
    ..Biol. 11(2001) 1358] exhibit normal levels of ptf1a. This indicates that hedgehog signaling plays a different genetic role in the specification of the anteroventral (mostly exocrine) and posterodorsal (endocrine) pancreatic anlagen. ..
  19. Flasse L, Pirson J, Stern D, Von Berg V, Manfroid I, Peers B, et al. Ascl1b and Neurod1, instead of Neurog3, control pancreatic endocrine cell fate in zebrafish. BMC Biol. 2013;11:78 pubmed publisher
    ..It is repressed by Notch signaling that prevents pancreatic cell differentiation by maintaining precursors in an undifferentiated state...
  20. Stetsyuk V, Peers B, Mavropoulos A, Verbruggen V, Thisse B, Thisse C, et al. Calsenilin is required for endocrine pancreas development in zebrafish. Dev Dyn. 2007;236:1517-25 pubmed
    ..Taken together, our results show that zebrafish calsenilin is involved in endocrine cell differentiation and morphogenesis within the pancreas. ..
  21. Ellertsdottir E, Ganz J, Durr K, Loges N, Biemar F, Seifert F, et al. A mutation in the zebrafish Na,K-ATPase subunit atp1a1a.1 provides genetic evidence that the sodium potassium pump contributes to left-right asymmetry downstream or in parallel to nodal flow. Dev Dyn. 2006;235:1794-808 pubmed
    ..Therefore, the Na,K-ATPase is required downstream or in parallel to monocilia function during initiation of left-right asymmetry in zebrafish. ..
  22. Anderson K, Singer R, Balderes D, Hernandez Lagunas L, Johnson C, Artinger K, et al. The L6 domain tetraspanin Tm4sf4 regulates endocrine pancreas differentiation and directed cell migration. Development. 2011;138:3213-24 pubmed publisher
    ..Identification of a role for Tm4sf4 during endocrine differentiation provides insight into islet progenitor cell behaviors and potential targetable regenerative mechanisms. ..
  23. Qin W, Chen Z, Zhang Y, Yan R, Yan G, Li S, et al. Nom1 mediates pancreas development by regulating ribosome biogenesis in zebrafish. PLoS ONE. 2014;9:e100796 pubmed publisher
    ..This suggests that targeting Pp1? into the nucleolus by Nom1 is important for pancreatic proliferation. Altogether, our studies revealed a new mechanism involving Nom1 in controlling vertebrate exocrine pancreas formation. ..
  24. Li Z, Wen C, Peng J, Korzh V, Gong Z. Generation of living color transgenic zebrafish to trace somatostatin-expressing cells and endocrine pancreas organization. Differentiation. 2009;77:128-34 pubmed publisher
    ..in insulin (Ins)-producing beta-cells, Tg(ins:gfp) and Tg(ins:rfp), in combination with immunodetection of glucagon (Gcg)-producing alpha-cells and pancreatic polypeptide (PP)-producing PP-cells, the organization and composition ..
  25. Park C, Moon M, Park S, Kim D, Cho E, Millar R, et al. A novel glucagon-related peptide (GCRP) and its receptor GCRPR account for coevolution of their family members in vertebrates. PLoS ONE. 2013;8:e65420 pubmed publisher
    The glucagon (GCG) peptide family consists of GCG, glucagon-like peptide 1 (GLP1), and GLP2, which are derived from a common GCG precursor, and the glucose-dependent insulinotropic polypeptide (GIP)...
  26. Djiotsa J, Verbruggen V, Giacomotto J, Ishibashi M, Manning E, Rinkwitz S, et al. Pax4 is not essential for beta-cell differentiation in zebrafish embryos but modulates alpha-cell generation by repressing arx gene expression. BMC Dev Biol. 2012;12:37 pubmed publisher
    ..These data suggests that the main original function of Pax4 during vertebrate evolution was to modulate the number of pancreatic ?-cells and its role in ?-cells differentiation appeared later in vertebrate evolution. ..
  27. Chow B, Moon T, Hoo R, Yeung C, MULLER M, Christos P, et al. Identification and characterization of a glucagon receptor from the goldfish Carassius auratus: implications for the evolution of the ligand specificity of glucagon receptors in vertebrates. Endocrinology. 2004;145:3273-88 pubmed
    ..In this paper we describe the isolation, functional, and phylogenetic characterization of the glucagon receptor from the goldfish Carassius auratus (Teleostei, order Cypriniformes), and compare its ligand specificity ..
  28. Zhao F, Jiang G, Wei P, Wang H, Ru S. Bisphenol S exposure impairs glucose homeostasis in male zebrafish (Danio rerio). Ecotoxicol Environ Saf. 2018;147:794-802 pubmed publisher
    ..Plasma insulin levels and expression of preproinsulin and glucagon genes in the visceral tissue were also evaluated...
  29. Pisharath H, Rhee J, Swanson M, Leach S, Parsons M. Targeted ablation of beta cells in the embryonic zebrafish pancreas using E. coli nitroreductase. Mech Dev. 2007;124:218-29 pubmed
  30. Lodh S, Hostelley T, Leitch C, O Hare E, Zaghloul N. Differential effects on β-cell mass by disruption of Bardet-Biedl syndrome or Alstrom syndrome genes. Hum Mol Genet. 2016;25:57-68 pubmed publisher
    ..Taken together, these findings implicate discrepant production and maintenance of β-cells in the differential susceptibility to diabetes found between these two genetic syndromes. ..
  31. Falcinelli S, Rodiles A, Unniappan S, Picchietti S, Gioacchini G, Merrifield D, et al. Probiotic treatment reduces appetite and glucose level in the zebrafish model. Sci Rep. 2016;6:18061 pubmed publisher
    ..rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation. ..
  32. Vaccari E, Deflorian G, Bernardi E, Pauls S, Tiso N, Bortolussi M, et al. prep1.2 and aldh1a2 participate to a positive loop required for branchial arches development in zebrafish. Dev Biol. 2010;343:94-103 pubmed publisher
    ..As the paralogue gene prep1.1 is more important in hindbrain patterning and neural crest chondrogenesis, we provide evidence of a functional specialization of prep genes in zebrafish head segmentation and morphogenesis...
  33. Ragvin A, Moro E, Fredman D, Navratilova P, Drivenes Ø, Engström P, et al. Long-range gene regulation links genomic type 2 diabetes and obesity risk regions to HHEX, SOX4, and IRX3. Proc Natl Acad Sci U S A. 2010;107:775-80 pubmed publisher
    ..number of pancreatic ghrelin-producing epsilon cells and decreased the number of insulin-producing beta-cells and glucagon-producing alpha-cells, thereby suggesting a direct link of pancreatic IRX3 function to both obesity and type 2 ..
  34. Dalgin G, Prince V. Differential levels of Neurod establish zebrafish endocrine pancreas cell fates. Dev Biol. 2015;402:81-97 pubmed publisher
    ..While Neurod plays a role in the differentiation of all endocrine cells, we find that differentiation of glucagon-expressing alpha cells is disrupted by a minor reduction in Neurod levels, whereas differentiation of insulin-..
  35. Li M, Page McCaw P, Chen W. FGF1 Mediates Overnutrition-Induced Compensatory β-Cell Differentiation. Diabetes. 2016;65:96-109 pubmed publisher
    ..Thus, the recently discovered antidiabetes function of FGF1 may act partially through increasing β-cell differentiation. ..
  36. Mommsen T, Mojsov S. Glucagon-like peptide-1 activates the adenylyl cyclase system in rockfish enterocytes and brain membranes. Comp Biochem Physiol B Biochem Mol Biol. 1998;121:49-56 pubmed
    b>Glucagon-like peptide (GLP) exerts important physiological functions in fish liver, but extrahepatic sites of action and physiological roles have been largely ignored...
  37. Wyett G, Gibert Y, Ellis M, Castillo H, Jan Kaslin -, Aston Mourney K. Metformin, beta-cell development, and novel processes following beta-cell ablation in zebrafish. Endocrine. 2018;59:419-425 pubmed publisher
    ..Further metformin significantly increased beta-cell number. Following beta-cell ablation, both glucagon and somatostatin expression were upregulated (>2-fold)...
  38. Veneman W, de Sonneville J, van der Kolk K, Ordas A, Al Ars Z, Meijer A, et al. Analysis of RNAseq datasets from a comparative infectious disease zebrafish model using GeneTiles bioinformatics. Immunogenetics. 2015;67:135-47 pubmed publisher
    ..In addition, we have implemented the DEXSeq module in the GeneTiles software to identify genes, such as glucagon A, that are differentially spliced under infection conditions...
  39. Argout X, Fouet O, Wincker P, Gramacho K, Legavre T, Sabau X, et al. Towards the understanding of the cocoa transcriptome: Production and analysis of an exhaustive dataset of ESTs of Theobroma cacao L. generated from various tissues and under various conditions. BMC Genomics. 2008;9:512 pubmed publisher
    ..cacao. This EST collection represents a unique and important molecular resource for T. cacao study and improvement, facilitating the discovery of candidate genes for important T. cacao trait variation...
  40. Li Z, Korzh V, Gong Z. DTA-mediated targeted ablation revealed differential interdependence of endocrine cell lineages in early development of zebrafish pancreas. Differentiation. 2009;78:241-52 pubmed publisher
    ..We found that ablation of beta-cells resulted in a reduction of not only beta-cells but also glucagon-producing alpha-cells; in contrast, delta-cells were largely unaffected...
  41. Falcinelli S, Rodiles A, Hatef A, Picchietti S, Cossignani L, Merrifield D, et al. Dietary lipid content reorganizes gut microbiota and probiotic L. rhamnosus attenuates obesity and enhances catabolic hormonal milieu in zebrafish. Sci Rep. 2017;7:5512 pubmed publisher
  42. Zhou L, Irwin D. Fish proglucagon genes have differing coding potential. Comp Biochem Physiol B Biochem Mol Biol. 2004;137:255-64 pubmed
    ..of the duplicated fish proglucagon genes indicates that one of the two genes is predicted to encode glucagon, GLP-1 and GLP-2...
  43. Ye L, Robertson M, Hesselson D, Stainier D, Anderson R. Glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis. Development. 2015;142:1407-17 pubmed publisher
    ..In murine models of diabetes, glucagon-secreting alpha cells transdifferentiate into insulin-secreting beta cells following targeted beta cell depletion,..
  44. Liu D, Tsai S, Lin B, Jiang Y, Wang W. Fibroblast growth factor receptor 2c signaling is required for intestinal cell differentiation in zebrafish. PLoS ONE. 2013;8:e58310 pubmed publisher
    ..These findings provide new evidences that Fgf signaling is required for the differentiation of intestinal cells in the zebrafish developing gut. ..
  45. Flasse L, Stern D, Pirson J, Manfroid I, Peers B, Voz M. The bHLH transcription factor Ascl1a is essential for the specification of the intestinal secretory cells and mediates Notch signaling in the zebrafish intestine. Dev Biol. 2013;376:187-97 pubmed publisher
    ..This highlights the diversity in the ARP/ASCL family members acting as cell fate determinants downstream from Notch signaling. ..
  46. Cruz S, Tseng Y, Kaiya H, Hwang P. Ghrelin affects carbohydrate-glycogen metabolism via insulin inhibition and glucagon stimulation in the zebrafish (Danio rerio) brain. Comp Biochem Physiol A Mol Integr Physiol. 2010;156:190-200 pubmed publisher
    ..Ligand-receptor synthesis of INS (zinsa; zins-r1 and zins-r2) significantly decreased, while glucagon (GCG) (zgcgb1 and zgcgb2; zgcg-r1 and zgcg-r2) exhibited a significant transient increase...
  47. Chen S, Huang J, Yuan G. siRNA specific to Pdx-1 disturbed the formation of the islet in early zebrafish embryos. J Huazhong Univ Sci Technolog Med Sci. 2007;27:639-42 pubmed publisher
    ..Pdx-1 played multiple roles in maintaining the phenotype of the islet during embryogenesis in zebrafish. ..
  48. Dupret B, Volkel P, Vennin C, Toillon R, Le Bourhis X, Angrand P. The histone lysine methyltransferase Ezh2 is required for maintenance of the intestine integrity and for caudal fin regeneration in zebrafish. Biochim Biophys Acta Gene Regul Mech. 2017;1860:1079-1093 pubmed publisher
    ..In addition, ezh2-deficient mutants fail to properly regenerate their spinal cord after caudal fin transection suggesting that Ezh2 and H3K27me3 methylation might also be involved in the process of regeneration in zebrafish. ..
  49. McGonnell I, Fowkes R. Fishing for gene function--endocrine modelling in the zebrafish. J Endocrinol. 2006;189:425-39 pubmed
    ..We anticipate that the use of these techniques will make the zebrafish a prominent model in endocrine research in the coming years. ..
  50. Wang Z, Mao Y, Cui T, Tang D, Wang X. Impact of a combined high cholesterol diet and high glucose environment on vasculature. PLoS ONE. 2013;8:e81485 pubmed publisher
    ..The zebrafish model with HCD-HG treatment was characterized by significantly increased tissue levels of insulin, glucagon, glucose, total triglyceride and cholesterol...
  51. Michel M, Page McCaw P, Chen W, Cone R. Leptin signaling regulates glucose homeostasis, but not adipostasis, in the zebrafish. Proc Natl Acad Sci U S A. 2016;113:3084-9 pubmed publisher
  52. Won M, Ro H, Dawid I. Lnx2 ubiquitin ligase is essential for exocrine cell differentiation in the early zebrafish pancreas. Proc Natl Acad Sci U S A. 2015;112:12426-31 pubmed publisher
    ..Further, the complex relationships among genotype, phenotype, and morpholino effect in this case may be instructive in the ongoing consideration of morpholino use. ..
  53. Li M, Dean E, Zhao L, Nicholson W, Powers A, Chen W. Glucagon receptor inactivation leads to α-cell hyperplasia in zebrafish. J Endocrinol. 2015;227:93-103 pubmed publisher
    b>Glucagon antagonism is a potential treatment for diabetes. One potential side effect is α-cell hyperplasia, which has been noted in several approaches to antagonize glucagon action...