Genomes and Genes
Gene Symbol: Gcg
Alias: GLP-1, Glu, PPG, glucagon, glucagon-like peptide I
- Kokubu H, Ohtsuka T, Kageyama R. Mash1 is required for neuroendocrine cell development in the glandular stomach. Genes Cells. 2008;13:41-51 pubmed publisher..Neurogenin3 (Ngn3), which is known to regulate formation of subsets of gastric neuroendocrine cells (gastrin-, glucagon- and somatostatin-producing cells), is expressed normally in the Mash1-null stomach...
- Prasadan K, Koizumi M, Tulachan S, Shiota C, Lath N, Paredes J, et al. The expression and function of glucose-dependent insulinotropic polypeptide in the embryonic mouse pancreas. Diabetes. 2011;60:548-54 pubmed publisher..insulinotropic polypeptide (GIP) is a member of a structurally related group of hormones that also includes glucagon, glucagon-like peptides, and secretin. GIP is an incretin, known to modulate glucose-induced insulin secretion...
- Murtaugh L, Law A, Dor Y, Melton D. Beta-catenin is essential for pancreatic acinar but not islet development. Development. 2005;132:4663-74 pubmed..Thus, our data are consistent with a crucial role for canonical Wnt signals in acinar lineage specification and differentiation. ..
- Pulkkinen M, Spencer Dene B, Dickson C, Otonkoski T. The IIIb isoform of fibroblast growth factor receptor 2 is required for proper growth and branching of pancreatic ductal epithelium but not for differentiation of exocrine or endocrine cells. Mech Dev. 2003;120:167-75 pubmed..Our results thus suggest that Fgfr2b-mediated signaling plays a major role in pancreatic ductal proliferation and branching morphogenesis, but has little effect on endocrine and exocrine differentiation. ..
- Chiang M, Melton D. Single-cell transcript analysis of pancreas development. Dev Cell. 2003;4:383-93 pubmed..This form of single-cell transcriptional analysis can be applied to any developmental process or tissue to characterize distinct cell types. ..
- Suzuki A, Nakauchi H, Taniguchi H. Glucagon-like peptide 1 (1-37) converts intestinal epithelial cells into insulin-producing cells. Proc Natl Acad Sci U S A. 2003;100:5034-9 pubmedb>Glucagon-like peptide (GLP) 1 is produced through posttranslational processing of proglucagon and acts as a regulator of various homeostatic events...
- Hart A, Papadopoulou S, Edlund H. Fgf10 maintains notch activation, stimulates proliferation, and blocks differentiation of pancreatic epithelial cells. Dev Dyn. 2003;228:185-93 pubmed..Together, our data suggest a role for FGF10/FGFR2b signalling in regulation of pancreatic cell proliferation and differentiation and that FGF10/FGFR2b signalling affects the Notch-mediated lateral inhibition pathway. ..
- Mellitzer G, Bonne S, Luco R, Van De Casteele M, Lenne Samuel N, Collombat P, et al. IA1 is NGN3-dependent and essential for differentiation of the endocrine pancreas. EMBO J. 2006;25:1344-52 pubmed..of Ngn3 function as inhibition of IA1 expression in embryonic pancreas decreases the formation of insulin- and glucagon-positive cells by 40%, while its ectopic expression amplifies neuroendocrine cell differentiation by Ngn3 in ..
- Diaferia G, Jimenez Caliani A, Ranjitkar P, Yang W, Hardiman G, Rhodes C, et al. ?1 integrin is a crucial regulator of pancreatic ?-cell expansion. Development. 2013;140:3360-72 pubmed publisher..Collectively, our results demonstrate that ?1 integrin receptors function as crucial positive regulators of ?-cell expansion. ..
- Kordowich S, Collombat P, Mansouri A, Serup P. Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin/ghrelin co-expressing cell lineage. BMC Dev Biol. 2011;11:52 pubmed publisher..Our analysis also suggests that one of the coupled functions of Nkx2.2 and Pax4 is to counteract Arx gene activity in early committed beta-cells. ..
- Mastracci T, Wilcox C, Arnés L, Panea C, Golden J, MAY C, et al. Nkx2.2 and Arx genetically interact to regulate pancreatic endocrine cell development and endocrine hormone expression. Dev Biol. 2011;359:1-11 pubmed publisher..Together, these experiments identify novel genetic interactions between Nkx2.2 and Arx within the endocrine progenitor cells that ensure the correct specification and regulation of endocrine hormone-producing cells. ..
- Lynn F, Skewes Cox P, Kosaka Y, McManus M, Harfe B, German M. MicroRNA expression is required for pancreatic islet cell genesis in the mouse. Diabetes. 2007;56:2938-45 pubmed..The expression of a unique profile of miRNAs is required during pancreas development and is necessary for beta-cell formation. ..
- Wang Q, Elghazi L, Martin S, Martins I, Srinivasan R, Geng X, et al. Ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and duodenum. Dev Dyn. 2008;237:51-61 pubmed..that the mutant islets are largely composed of a distinctive endocrine cell type that expresses ghrelin, glucagon, islet amyloid polypeptide (IAPP), and low levels of Pdx1...
- Georgia S, Bhushan A. Beta cell replication is the primary mechanism for maintaining postnatal beta cell mass. J Clin Invest. 2004;114:963-8 pubmed
- Papadopoulou S, Edlund H. Attenuated Wnt signaling perturbs pancreatic growth but not pancreatic function. Diabetes. 2005;54:2844-51 pubmed..Collectively, our data provide evidence that Wnt signaling is required for pancreatic growth but not adult beta-cell function. ..
- Artner I, Hang Y, Mazur M, Yamamoto T, Guo M, Lindner J, et al. MafA and MafB regulate genes critical to beta-cells in a unique temporal manner. Diabetes. 2010;59:2530-9 pubmed publisher..Our results provide insight into the sequential manner by which MafA and MafB regulate islet ?-cell formation and maturation. ..
- Seymour P, Freude K, Dubois C, Shih H, Patel N, Sander M. A dosage-dependent requirement for Sox9 in pancreatic endocrine cell formation. Dev Biol. 2008;323:19-30 pubmed publisher..Our findings therefore suggest that defective endocrine specification might underlie the pancreatic phenotype of individuals with CD. ..
- Collombat P, Hecksher Sørensen J, Broccoli V, Krull J, Ponte I, Mundiger T, et al. The simultaneous loss of Arx and Pax4 genes promotes a somatostatin-producing cell fate specification at the expense of the alpha- and beta-cell lineages in the mouse endocrine pancreas. Development. 2005;132:2969-80 pubmed..Finally, our data provide evidence that both Arx and Pax4 act as transcriptional repressors that control the expression level of one another, thereby mediating proper endocrine fate allocation. ..
- Smart N, Apelqvist A, Gu X, Harmon E, Topper J, Macdonald R, et al. Conditional expression of Smad7 in pancreatic beta cells disrupts TGF-beta signaling and induces reversible diabetes mellitus. PLoS Biol. 2006;4:e39 pubmed..Thus, our studies reveal that TGF-beta signaling is crucial for establishing and maintaining defining features of mature pancreatic beta cells. ..
- Soyer J, Flasse L, Raffelsberger W, Beucher A, Orvain C, Peers B, et al. Rfx6 is an Ngn3-dependent winged helix transcription factor required for pancreatic islet cell development. Development. 2010;137:203-12 pubmed publisher..Loss-of-function studies in zebrafish revealed that rfx6 is required for the differentiation of glucagon-, ghrelin- and somatostatin-expressing cells, which, in the absence of rfx6, are blocked at the progenitor stage...
- Li S, Francisco A, Munroe R, Schimenti J, Long Q. SEL1L deficiency impairs growth and differentiation of pancreatic epithelial cells. BMC Dev Biol. 2010;10:19 pubmed publisher..Together, these data suggest that Sel1l is essential for the growth and differentiation of endoderm-derived pancreatic epithelial cells during mouse embryonic development. ..
- Du A, Hunter C, Murray J, Noble D, Cai C, Evans S, et al. Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas. Diabetes. 2009;58:2059-69 pubmed publisher..These results demonstrate the requirement for Isl-1 in the maturation, proliferation, and survival of the second wave of hormone-producing islet cells. ..
- Haumaitre C, Barbacci E, Jenny M, Ott M, Gradwohl G, Cereghini S. Lack of TCF2/vHNF1 in mice leads to pancreas agenesis. Proc Natl Acad Sci U S A. 2005;102:1490-5 pubmed..This study provides further insights into early molecular events controlling pancreas development and may contribute to the development of cell-replacement strategies for diabetes. ..
- Juhl K, Sarkar S, Wong R, Jensen J, Hutton J. Mouse pancreatic endocrine cell transcriptome defined in the embryonic Ngn3-null mouse. Diabetes. 2008;57:2755-61 pubmed publisher..The deposited data provide a rich resource that can be used to address diverse questions related to islet developmental and cell biology and the pathogenesis of type 1 and 2 diabetes. ..
- Collombat P, Hecksher Sørensen J, Krull J, Berger J, Riedel D, Herrera P, et al. Embryonic endocrine pancreas and mature beta cells acquire alpha and PP cell phenotypes upon Arx misexpression. J Clin Invest. 2007;117:961-70 pubmed..in adult mice, the misexpression of Arx, rather than its overexpression, promotes a conversion of beta cells into glucagon- or PP-producing cells in vivo...
- Johansson J, Voss U, Kesavan G, Kostetskii I, Wierup N, Radice G, et al. N-cadherin is dispensable for pancreas development but required for beta-cell granule turnover. Genesis. 2010;48:374-81 pubmed publisher..The number of insulin secretory granules is significantly reduced in N-cadherin-deficient beta-cells, and as a consequence insulin secretion is decreased. ..
- Carbe C, Hertzler Schaefer K, Zhang X. The functional role of the Meis/Prep-binding elements in Pax6 locus during pancreas and eye development. Dev Biol. 2012;363:320-9 pubmed publisher..and quantitative RT-PCR showed that the Pax6(?PE/?PE) pancreata had a significant decrease in Pax6, glucagon, and insulin expression, while no further reductions were observed in the Pax6(?DP/?DP) mice, indicating that ..
- Jacquemin P, Durviaux S, Jensen J, Godfraind C, Gradwohl G, Guillemot F, et al. Transcription factor hepatocyte nuclear factor 6 regulates pancreatic endocrine cell differentiation and controls expression of the proendocrine gene ngn3. Mol Cell Biol. 2000;20:4445-54 pubmed..They also suggest that HNF-6 is a candidate gene for diabetes mellitus in humans. ..
- Maestro M, Boj S, Luco R, Pierreux C, Cabedo J, Servitja J, et al. Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell domain of the embryonic pancreas. Hum Mol Genet. 2003;12:3307-14 pubmed..These findings define a precursor cellular stage of the embryonic pancreas and place Hnf1beta in a genetic hierarchy that regulates the generation of pancreatic endocrine cells. ..
- Hansotia T, Drucker D. GIP and GLP-1 as incretin hormones: lessons from single and double incretin receptor knockout mice. Regul Pept. 2005;128:125-34 pubmedGlucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut-derived incretins secreted in response to nutrient ingestion...
- Harmon E, Apelqvist A, Smart N, Gu X, Osborne D, Kim S. GDF11 modulates NGN3+ islet progenitor cell number and promotes beta-cell differentiation in pancreas development. Development. 2004;131:6163-74 pubmed..Thus, our studies reveal mechanisms by which GDF11 regulates the production and maturation of islet progenitor cells in pancreas development. ..
- Artner I, Le Lay J, Hang Y, Elghazi L, Schisler J, Henderson E, et al. MafB: an activator of the glucagon gene expressed in developing islet alpha- and beta-cells. Diabetes. 2006;55:297-304 pubmed..pancreas, MafB is only expressed in islet alpha-cells and contributes to cell type-specific expression of the glucagon gene through activation of a conserved control element found between nucleotides -77 to -51...
- Gannon M, Ray M, Van Zee K, Rausa F, Costa R, Wright C. Persistent expression of HNF6 in islet endocrine cells causes disrupted islet architecture and loss of beta cell function. Development. 2000;127:2883-95 pubmed
- Wang S, Hecksher Sorensen J, Xu Y, Zhao A, Dor Y, Rosenberg L, et al. Myt1 and Ngn3 form a feed-forward expression loop to promote endocrine islet cell differentiation. Dev Biol. 2008;317:531-40 pubmed publisher..Myt1b induces glucagon expression by potentiating Ngn3 transcription in pancreatic progenitors...
- Furuta M, Zhou A, Webb G, Carroll R, Ravazzola M, Orci L, et al. Severe defect in proglucagon processing in islet A-cells of prohormone convertase 2 null mice. J Biol Chem. 2001;276:27197-202 pubmed..Their islets show marked alpha (A)-cell hyperplasia, suggesting a possible defect in glucagon processing (Furuta, M., Yano, H., Zhou, A., Rouille, Y., Holst, J., Carroll, R., Ravazzola, M., Orci, L...
- Henseleit K, Nelson S, Kuhlbrodt K, Hennings J, Ericson J, Sander M. NKX6 transcription factor activity is required for alpha- and beta-cell development in the pancreas. Development. 2005;132:3139-49 pubmed..We demonstrate that expression of Myt1 depends on overall Nkx6 gene dose, and therefore identify Myt1 as a possible downstream target of Nkx6 genes in the endocrine differentiation pathway. ..
- Brissova M, Shostak A, Shiota M, Wiebe P, Poffenberger G, Kantz J, et al. Pancreatic islet production of vascular endothelial growth factor--a is essential for islet vascularization, revascularization, and function. Diabetes. 2006;55:2974-85 pubmed..Factors modulating VEGF-A expression may influence islet vascularity and, consequently, the amount of insulin delivered into the systemic circulation. ..
- Dubois C, Shih H, Seymour P, Patel N, Behrmann J, Ngo V, et al. Sox9-haploinsufficiency causes glucose intolerance in mice. PLoS ONE. 2011;6:e23131 pubmed publisher..Our findings show Sox9 plays an important role in endocrine development by maintaining Ngn3 and Pdx1 expression. Glucose intolerance in Sox9-haploinsufficient mice suggests that mutations in Sox9 could play a role in diabetes in humans. ..
- Yang Y, Thorel F, Boyer D, Herrera P, Wright C. Context-specific ?- to-?-cell reprogramming by forced Pdx1 expression. Genes Dev. 2011;25:1680-5 pubmed publisher..More surprisingly, almost all remaining Pdx1-containing glucagon/Arx-producing cells underwent a fairly rapid conversion at postnatal stages, through glucagon-insulin double ..
- Yoshitomi H, Zaret K. Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Development. 2004;131:807-17 pubmed..Additionally, we find that endothelial cells are necessary for the induction of both the insulin and glucagon genes.
- Miyatsuka T, Kosaka Y, Kim H, German M. Neurogenin3 inhibits proliferation in endocrine progenitors by inducing Cdkn1a. Proc Natl Acad Sci U S A. 2011;108:185-90 pubmed publisher..These studies reveal a crucial role for Neurog3 in regulating the cell cycle during the differentiation of islet cells and demonstrate that the subsequent down-regulation of Neurog3 allows the mature islet cell population to expand. ..
- Nishimura W, Rowan S, Salameh T, Maas R, Bonner Weir S, Sell S, et al. Preferential reduction of beta cells derived from Pax6-MafB pathway in MafB deficient mice. Dev Biol. 2008;314:443-56 pubmed publisher..deficiency, as manifest in the Pax6(Sey-Neu) allele, reduced not only the number of cells expressing insulin or glucagon, but also the number of MafB, PDX-1 and MafA expressing cells...
- Jang H, Kokrashvili Z, Theodorakis M, Carlson O, Kim B, Zhou J, et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A. 2007;104:15069-74 pubmedb>Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility. How glucose given orally, but not systemically, induces GLP-1 secretion is unknown...
- Ouhilal S, Vuguin P, Cui L, Du X, Gelling R, Reznik S, et al. Hypoglycemia, hyperglucagonemia, and fetoplacental defects in glucagon receptor knockout mice: a role for glucagon action in pregnancy maintenance. Am J Physiol Endocrinol Metab. 2012;302:E522-31 pubmed publisher..predispose to infertility as well as adverse pregnancy outcomes; however, little is known about the role of glucagon signaling in reproduction...
- Lee N, Sowa H, Hinoi E, Ferron M, Ahn J, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130:456-69 pubmed..By revealing that the skeleton exerts an endocrine regulation of sugar homeostasis this study expands the biological importance of this organ and our understanding of energy metabolism. ..
- Desgraz R, Herrera P. Pancreatic neurogenin 3-expressing cells are unipotent islet precursors. Development. 2009;136:3567-74 pubmed publisher..We propose a model whereby Ngn3(+) cells are monotypic (i.e. unipotent) precursors, and use this paradigm to refocus ideas on how cell number and type must be regulated in building complete islets of Langerhans. ..
- Vincent M, Guz Y, Rozenberg M, Webb G, Furuta M, Steiner D, et al. Abrogation of protein convertase 2 activity results in delayed islet cell differentiation and maturation, increased alpha-cell proliferation, and islet neogenesis. Endocrinology. 2003;144:4061-9 pubmed..However, the IN(+) cells of d 15 PC2 mutant mice coexpressed glucagon, as did the first appearing beta-cells of controls...
- Heiser P, Lau J, Taketo M, Herrera P, Hebrok M. Stabilization of beta-catenin impacts pancreas growth. Development. 2006;133:2023-32 pubmed..Taken together, these data suggest a previously unappreciated temporal/spatial role for beta-catenin signaling in the regulation of pancreas organ growth. ..
- Watanabe C, Seino Y, Miyahira H, Yamamoto M, Fukami A, Ozaki N, et al. Remodeling of hepatic metabolism and hyperaminoacidemia in mice deficient in proglucagon-derived peptides. Diabetes. 2012;61:74-84 pubmed publisherb>Glucagon is believed to be one of the most important peptides for upregulating blood glucose levels...
- Zhang W, Feng D, Li Y, Iida K, McGrath B, Cavener D. PERK EIF2AK3 control of pancreatic beta cell differentiation and proliferation is required for postnatal glucose homeostasis. Cell Metab. 2006;4:491-7 pubmed
- Kim S, Hebrok M, Li E, Oh S, Schrewe H, Harmon E, et al. Activin receptor patterning of foregut organogenesis. Genes Dev. 2000;14:1866-71 pubmed..Thus, activin receptor-mediated signaling regulates axial patterning, cell differentiation, and function of foregut-derived organs. ..
- Gosmain Y, Avril I, Mamin A, Philippe J. Pax-6 and c-Maf functionally interact with the alpha-cell-specific DNA element G1 in vivo to promote glucagon gene expression. J Biol Chem. 2007;282:35024-34 pubmedSpecific expression of the glucagon gene in the rat pancreas requires the presence of the G1 element localized at -100/-49 base pairs on the promoter...
- Katsuma S, Hirasawa A, Tsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun. 2005;329:386-90 pubmed..In this study, we show that bile acids promote glucagon-like peptide-1 (GLP-1) secretion through TGR5 in a murine enteroendocrine cell line STC-1...
- Nekrep N, Wang J, Miyatsuka T, German M. Signals from the neural crest regulate beta-cell mass in the pancreas. Development. 2008;135:2151-60 pubmed publisher..2 form a non-cell-autonomous feedback loop that links the neural crest with the pancreatic epithelium, regulates the size of the beta-cell population, and thereby impacts insulin-secretory capacity and energy homeostasis. ..
- Heller R, Stoffers D, Liu A, Schedl A, Crenshaw E, Madsen O, et al. The role of Brn4/Pou3f4 and Pax6 in forming the pancreatic glucagon cell identity. Dev Biol. 2004;268:123-34 pubmed..and paired-homeodomain transcription factors, respectively, that are expressed in the brain and the glucagon-expressing cells in the pancreas...
- Kilic G, Wang J, Sosa Pineda B. Osteopontin is a novel marker of pancreatic ductal tissues and of undifferentiated pancreatic precursors in mice. Dev Dyn. 2006;235:1659-67 pubmed..Finally, the maintenance of Opn expression in pancreatic tissues of adults argues for a possible function of this protein in injury and pathologic responses. ..
- Collombat P, Mansouri A, Hecksher Sorensen J, Serup P, Krull J, Gradwohl G, et al. Opposing actions of Arx and Pax4 in endocrine pancreas development. Genes Dev. 2003;17:2591-603 pubmed..We propose that the antagonistic functions of Arx and Pax4 for proper islet cell specification are related to the pancreatic levels of the respective transcripts. ..
- Wideman R, Covey S, Webb G, Drucker D, Kieffer T. A switch from prohormone convertase (PC)-2 to PC1/3 expression in transplanted alpha-cells is accompanied by differential processing of proglucagon and improved glucose homeostasis in mice. Diabetes. 2007;56:2744-52 pubmedb>Glucagon, which raises blood glucose levels by stimulating hepatic glucose production, is produced in alpha-cells via cleavage of proglucagon by prohormone convertase (PC)-2...
- Adachi T, Tanaka T, Takemoto K, Koshimizu T, Hirasawa A, Tsujimoto G. Free fatty acids administered into the colon promote the secretion of glucagon-like peptide-1 and insulin. Biochem Biophys Res Commun. 2006;340:332-7 pubmedWe examined whether free fatty acids (FFAs) promote glucagon-like peptide-1 (GLP-1) secretion when administered into the intestinal tract...
- Bhushan A, Itoh N, Kato S, Thiery J, Czernichow P, Bellusci S, et al. Fgf10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesis. Development. 2001;128:5109-17 pubmed..These results indicate that Fgf10 signalling is required for the normal development of the pancreas and should prove useful in devising methods to expand pancreatic progenitor cells. ..
- Miettinen P, Huotari M, Koivisto T, Ustinov J, Palgi J, Rasilainen S, et al. Impaired migration and delayed differentiation of pancreatic islet cells in mice lacking EGF-receptors. Development. 2000;127:2617-27 pubmed..Upregulated PAI-1 production and decreased gelatinolytic activity correlated to this migration defect. An intact EGF-R pathway appears to be a prerequisite for normal pancreatic development. ..
- Fukami A, Seino Y, Ozaki N, Yamamoto M, Sugiyama C, Sakamoto Miura E, et al. Ectopic expression of GIP in pancreatic ?-cells maintains enhanced insulin secretion in mice with complete absence of proglucagon-derived peptides. Diabetes. 2013;62:510-8 pubmed publisherb>Glucagon and glucagon-like peptide-1 (GLP-1) are produced in pancreatic ?-cells and enteroendocrine L-cells, respectively, in a tissue-specific manner from the same precursor, proglucagon, that is encoded by glucagon gene (Gcg), and play ..
- Vuguin P, Kedees M, Cui L, Guz Y, Gelling R, Nejathaim M, et al. Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation. Endocrinology. 2006;147:3995-4006 pubmedAlthough glucagon (GLU) plays a pivotal role in glucose homeostasis, its role in the regulation of fetal growth and maturation is poorly understood...
- Gannon M, Ables E, Crawford L, Lowe D, OFFIELD M, Magnuson M, et al. pdx-1 function is specifically required in embryonic beta cells to generate appropriate numbers of endocrine cell types and maintain glucose homeostasis. Dev Biol. 2008;314:406-17 pubmed..and adult mutant islets showed a dramatic reduction in the number of insulin(+) cells and an increase in both glucagon(+) and somatostatin(+) cells...
- Prado C, Pugh Bernard A, Elghazi L, Sosa Pineda B, Sussel L. Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas development. Proc Natl Acad Sci U S A. 2004;101:2924-9 pubmed..2 is essential for the differentiation of all insulin-producing beta cells and a subset of glucagon-producing alpha cells (1). Mice lacking Nkx2...
- Gao N, LeLay J, Vatamaniuk M, Rieck S, Friedman J, Kaestner K. Dynamic regulation of Pdx1 enhancers by Foxa1 and Foxa2 is essential for pancreas development. Genes Dev. 2008;22:3435-48 pubmed publisher..Thus, the regulation of Pdx1 expression by Foxa1 and Foxa2 is a key early event controlling the expansion and differentiation of the pancreatic primordia. ..
- Wang J, Elghazi L, Parker S, Kizilocak H, Asano M, Sussel L, et al. The concerted activities of Pax4 and Nkx2.2 are essential to initiate pancreatic beta-cell differentiation. Dev Biol. 2004;266:178-89 pubmed..This role of Pax4 appears to be accomplished via its genetic interaction with another homeobox gene, Nkx2.2. ..
- Xu Y, Wang S, Zhang J, Zhao A, Stanger B, Gu G. The fringe molecules induce endocrine differentiation in embryonic endoderm by activating cMyt1/cMyt3. Dev Biol. 2006;297:340-9 pubmed..These results suggest that Mfng-mediated repression of Notch signaling could serve as a trigger for endocrine islet differentiation. ..
- Gomez E, Pritchard C, Herbert T. cAMP-dependent protein kinase and Ca2+ influx through L-type voltage-gated calcium channels mediate Raf-independent activation of extracellular regulated kinase in response to glucagon-like peptide-1 in pancreatic beta-cells. J Biol Chem. 2002;277:48146-51 pubmedb>Glucagon like peptide-1 (GLP1) is a G(s)-coupled receptor agonist that exerts multiple effects on pancreatic beta-cells, including the stimulation of insulin gene expression and secretion...
- Hald J, Hjorth J, German M, Madsen O, Serup P, Jensen J. Activated Notch1 prevents differentiation of pancreatic acinar cells and attenuate endocrine development. Dev Biol. 2003;260:426-37 pubmed
- Mellitzer G, Beucher A, Lobstein V, Michel P, Robine S, Kedinger M, et al. Loss of enteroendocrine cells in mice alters lipid absorption and glucose homeostasis and impairs postnatal survival. J Clin Invest. 2010;120:1708-21 pubmed publisher..Our data help unravel the role of enteroendocrine cells and hormones in lipid absorption and maintenance of the intestinal epithelium. ..
- Nir T, Melton D, Dor Y. Recovery from diabetes in mice by beta cell regeneration. J Clin Invest. 2007;117:2553-61 pubmed..These results suggest that regenerative therapy for type 1 diabetes may be achieved if autoimmunity is halted using regeneration-compatible drugs. ..
- Lynn F, Smith S, Wilson M, Yang K, Nekrep N, German M. Sox9 coordinates a transcriptional network in pancreatic progenitor cells. Proc Natl Acad Sci U S A. 2007;104:10500-5 pubmed..These studies indicate that Sox9 plays a dual role in pancreatic progenitor cells: both maintaining a stable transcriptional network and supporting the programs by which these cells differentiate into distinct lineages. ..
- Schwitzgebel V, Scheel D, Conners J, Kalamaras J, Lee J, Anderson D, et al. Expression of neurogenin3 reveals an islet cell precursor population in the pancreas. Development. 2000;127:3533-42 pubmed
- Zhang H, Ackermann A, Gusarova G, Lowe D, Feng X, Kopsombut U, et al. The FoxM1 transcription factor is required to maintain pancreatic beta-cell mass. Mol Endocrinol. 2006;20:1853-66 pubmed..These results suggest that mechanisms regulating embryonic beta-cell proliferation differ from those used postnatally to maintain the differentiated cell population. ..
- Diao J, Asghar Z, Chan C, Wheeler M. Glucose-regulated glucagon secretion requires insulin receptor expression in pancreatic alpha-cells. J Biol Chem. 2005;280:33487-96 pubmed..However, much less is known about the role of the IR in alpha-cells. To assess the role of the IR in glucagon and insulin secretion, we engineered adeno-viruses for high efficiency small interference RNA (siRNA)-IR ..
- Wang S, Jensen J, Seymour P, Hsu W, Dor Y, Sander M, et al. Sustained Neurog3 expression in hormone-expressing islet cells is required for endocrine maturation and function. Proc Natl Acad Sci U S A. 2009;106:9715-20 pubmed publisher..These findings demonstrate that Neurog3 is required not only for initiating endocrine cell differentiation, but also for promoting islet cell maturation and maintaining islet function. ..
- Reimann F, Williams L, da Silva Xavier G, Rutter G, Gribble F. Glutamine potently stimulates glucagon-like peptide-1 secretion from GLUTag cells. Diabetologia. 2004;47:1592-601 pubmedb>Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are secreted from enteroendocrine L cells in response to nutrient ingestion...
- Hebrok M, Kim S, St Jacques B, McMahon A, Melton D. Regulation of pancreas development by hedgehog signaling. Development. 2000;127:4905-13 pubmed..Defects in hedgehog signaling may lead to congenital pancreatic malformations and glucose intolerance. ..
- Wang S, Yan J, Anderson D, Xu Y, Kanal M, Cao Z, et al. Neurog3 gene dosage regulates allocation of endocrine and exocrine cell fates in the developing mouse pancreas. Dev Biol. 2010;339:26-37 pubmed publisher..The control of Neurog3+ cell number and the Neurog3 threshold-dependent endocrine differentiation mechanism combine to select a specific proportion of pancreatic progenitor cells to adopt the islet cell fate. ..
- Fujitani Y, Fujitani S, Boyer D, Gannon M, Kawaguchi Y, Ray M, et al. Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation. Genes Dev. 2006;20:253-66 pubmed