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The Glucagon Gene and Its Expression

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Glucagon III

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 123))

Abstract

A new era in the knowledge of the physiology of the proglucagon-derived peptides and its producing cell has been opened by the cloning of the glucagon gene. This major step has allowed a better understanding of the structure of the glucagon precursor, proglucagon, and the discovery of two unexpected peptides, glucagon-like peptides-1 and -2 (GLP-1 and GLP-2).

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References

  • Alpert S, Hanahan D, Teitelman G (1988) Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons. Cell 53: 295–308

    Article  PubMed  CAS  Google Scholar 

  • Andrews PC, Ronner P (1986) Isolation and structures of glucagon and glucagon-like peptides from catfish pancreas. J Biol Chem 260: 3910–3914

    Google Scholar 

  • Andrews PC, Hawke DH, Lee TD, Legesse K, Noe BD, Schiverly JE (1986) Isolation and structure of the principal products of preproglucagon processing, including an amidated glucagon-like peptide. J Biol Chem 261: 8128–8133

    PubMed  CAS  Google Scholar 

  • Bani D, Biliotti G, Sacchi TB (1991) Morphological changes in the human endocrine pancreas induced by chronic excess of endogenous glucagon. Virchows Arch [B] Cell Pathol 60: 199–206

    Article  CAS  Google Scholar 

  • Bell GI (1986) The glucagon superfamily: precursor structure and gene organization. Peptides 7 [Suppl 11: 27–36

    Google Scholar 

  • Bell GI, Sanchez-Pescador R, Laybourn PJ, Najarian RC (1983a) Exon duplication and divergence in the human glucagon gene. Nature 304: 368–371

    Article  PubMed  CAS  Google Scholar 

  • Bell GI, Santerre RF, Mullenbach GT (1983b) Hamster preproglucagon contains the sequence of glucagon and two related peptides. Nature 302: 716–718

    Article  PubMed  CAS  Google Scholar 

  • Brubaker PL, Lee YC, Drucker DJ (1992) Alterations in proglucagon processing and inhibition of proglucagon gene expression in transgenic mice which contain a chimeric proglucagon SV-40 T antigen gene. J Biol Chem 267: 20728–20733

    PubMed  CAS  Google Scholar 

  • Caudy M, Vässin H, Brand M, Tuma R, Yan LY, Yan YN (1988) Daughterless, a drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex. Cell 55: 1061–1067

    Article  PubMed  CAS  Google Scholar 

  • Chen L, Komiya I, Inman L, O’Neil J, Appel M, Alam T, Unger RH (1989a) Molecular and cellular responses of islets during perturbations of glucose homeostasis determined by in situ hybridization histochemistry. J Clin Invest 84: 711–714

    Article  PubMed  CAS  Google Scholar 

  • Chen L, Komiya I, Inman L, Mckorkle K, Alam T, Unger RH (1989b) Effects of hypoglycemia and prolonged fasting on insulin and glucagon gene expression. Proc Natl Acad Sci USA 86: 1367–1371

    Article  PubMed  CAS  Google Scholar 

  • Cordier-Bussat M, Morel C, Philippe J (1995) Homologous DNA sequences and cellular factors are implicated in the control of glucagon and insulin gene expression. Mol Cell Biol 15: 3904–3916

    PubMed  CAS  Google Scholar 

  • Drucker DJ, Asa SL (1988) Glucagon gene expression in vertebrate brain. J Biol Chem 263: 13475–13478

    PubMed  CAS  Google Scholar 

  • Drucker DJ, Brubacker PL (1989) Proglucagon gene expression is regulated by a cAMP-dependent pathway in rat intestine. Proc Natl Acad Sci USA 86: 3953–3957

    Article  PubMed  CAS  Google Scholar 

  • Drucker DJ, Philippe J, Jepeal L, Habener JF (1987a) Cis-acting DNA sequence controls glucagon gene expression in pancreatic islet cells. Trans Assoc Am Physicians 100: 109–115

    PubMed  CAS  Google Scholar 

  • Drucker DJ, Philippe J, Jepeal L, Habener JF (1987b) Glucagon gene 5’-flanking sequences promote islet cell-specific glucagon gene transcription. J Biol Chem 262: 15659–15665

    PubMed  CAS  Google Scholar 

  • Drucker DJ, Campos R, Reynolds R, Stobie K, Brubaker PL (1991) The rat glucagon gene is regulated by a protein kinase A-dependent pathway in pancreatic islet cells. Endocrinology 128: 394–400

    Article  PubMed  CAS  Google Scholar 

  • Drucker DJ, Jin T, Asa SL, Young TA, Brubaker PL (1994) Activation of proglucagon gene transcription by protein kinase-A in a novel mouse enteroendocrine cell line. Mol Endocrinol 8: 1646–1655

    Article  PubMed  CAS  Google Scholar 

  • Efrat S, Teitelman G, Anwar M, Ruggiero D, Hanahan D (1988) Glucagon gene regulatory region directs oncoprotein expression to neurons and pancreatic alpha cells. Neuron 1: 605–613

    Article  PubMed  CAS  Google Scholar 

  • Gail Pollock H, Hamilton JW, Rouse JB, Ebner KE, Rawitch KB (1988) Isolation of peptide hormones from the pancreas of the bullfrog. J Biol Chem 263: 9746–9751

    Google Scholar 

  • Gajic D, Drucker DJ (1993) Multiple cis-acting domains mediate basal and adenosine 3’, 5’-monophosphate-dependent glucagon gene transcription in a mouse neuroendocrine cell line. Endocrinology 132: 1055–1323

    Article  PubMed  CAS  Google Scholar 

  • Giddings SJ, Carnaghi LR, Mooradian AD (1995) Age-related changes in pancreatic islet cell gene expression. Metabolism 44: 320–324

    Article  PubMed  CAS  Google Scholar 

  • Gittes GK, Rutter WJ (1992) Onset of cell-specific gene expression in the developing mouse pancreas. Proc Natl Acad Sci 89: 1128–1132

    Article  PubMed  CAS  Google Scholar 

  • Hasegawa S, Terazono K, Nata K, Takada T, Yamamoto H, Okamoto H (1990) Nucleotide sequence determination of chicken glucagon precursor cDNA. FEBS Lett 264: 117–120

    Article  PubMed  CAS  Google Scholar 

  • Heinrich G, Gros P, Habener JF (1984a) Glucagon gene sequence: four or six exons separate functional domains of rat preproglucagon. J Biol Chem 259: 14082–14084

    PubMed  CAS  Google Scholar 

  • Heinrich G, Gros P, Lund PK, Bentley RC, Habener JF (1984b) Preproglucagon mRNA: nucleotide and encoded amino acid sequences of the rat pancreatic cDNA. Endocrinology 115: 2176–2181.

    Article  PubMed  CAS  Google Scholar 

  • Herrera PL, Huarte J, Sanvito F, Meda P, Orci L, Vassalli JD (1991) Embryogenesis of the murine endocrine pancreas; early expression of pancreatic polypeptide gene. Development 113: 1257–1265

    PubMed  CAS  Google Scholar 

  • Herrera PL, Huarte J, Zufferey R, Nichols A, Mermillod B, Philippe J, Muniesa P, Sanvito F, Orci L, Vassalli JD (1994) Ablation of islet endocrine cells by targeted expression of hormone-promoter-driven toxigenes. Proc Natl Acad Sci USA 91: 12999–13003

    Article  PubMed  CAS  Google Scholar 

  • Hosoya M, Kimura C, Ogi K, Ohkubo S, Miyamoto Y, Kugoh H, Shimizu M, Onda H, Oshimura M, Arimura A, Fujino M (1992) Structure of the human pituitary adenylate cyclase activating polypeptide ( PACAP) gene. Biochim Biophys Acta 1129: 199–206

    PubMed  CAS  Google Scholar 

  • Inagaki N, Seino Y, Takeda J, Yano H, Yamada Y, Bell GI, Eddy RL, Fukushima Y, Byers MG, Shows TB, Imura H (1989) Gastric inhibitory polypeptide: structure and chromosomal localization of the human gene. Mol Endocrinol 3: 1014–1021

    Article  PubMed  CAS  Google Scholar 

  • Jonsson J, Carlsson L, Edlung T, Edlund H (1994) Insulin-promoter-factor 1 is required for pancreas development in mice. Nature 371: 606–609

    Article  PubMed  CAS  Google Scholar 

  • Kawai K, Unger RH (1982) Inhibition of glucagon secretion by exogenous glucagon in the isolated, perfused dog pancreas. Diabetes 31: 512–515

    Article  PubMed  CAS  Google Scholar 

  • Knepel W, Jepeal L, Habener JF (1990a) A pancreatic islet cell-specific enhancer-like element in the glucagon gene contains two domains binding distinct cellular proteins. J Biol Chem 265: 8725–8735

    PubMed  CAS  Google Scholar 

  • Knepel W, Chafitz J, Habener JF (1990b) Transcriptional activation of the rat glucagon gene by the cAMP-responsive element in pancreatic islet cells. Mol Cell Biol 10: 6799–6804

    PubMed  CAS  Google Scholar 

  • Knepel W, Vallejo M, Chafitz JA, Habener JF (1991) The pancreatic islet-specific glucagon G3 transcription factors recognize control elements in the rat somatostatin and insulin I genes. Mol Endocrinol 5: 1457–1466

    Article  PubMed  CAS  Google Scholar 

  • Kopin A, Wheeler MB, Nishitani J, McBride EW, Chang T, Chey WY, Leiter AB (1991) The secretin gene: evolutionary history, alternative splicing, and developmental regulation. Proc Natl Acad Sci USA 88: 5335–5339

    Article  PubMed  CAS  Google Scholar 

  • Koranyi L, James DE, Kraegen EW, Permutt MA (1992) Feedback inhibition of insulin gene expression by insulin. J Clin Invest 89: 432–436

    Article  PubMed  CAS  Google Scholar 

  • Kruse F, Rose SD, Swif GH, Hammer RE, McDonal RJ (1993) An endocrine-specific element is an integral component of an exocrine-specific pancreatic enhancer. Genes Dev 7: 774–786

    Article  PubMed  CAS  Google Scholar 

  • Lee YC, Asa SL, Drucker DJ (1992) Glucagon gene 5’-flanking sequences direct expression of simian virus 40 large T antigen to the intestine, producing carcinoma of the large bowel in transgenic mice. J Biol Chem 267: 10705–10708

    PubMed  CAS  Google Scholar 

  • Lee YC, Campos RV, Drucker DJ (1993) Region- and age-specific differences in proglucagon gene expression in the central nervous system of wild-type and glucagon-simian virus-40 T-antigen transgenic mice. Endocrinology 133: 171–177

    Article  PubMed  CAS  Google Scholar 

  • Lefèbvre PJ (1995) Glucagon and its family revisited. Diabetes Care 18: 715–730

    PubMed  Google Scholar 

  • Logothetopoulos J, Sharma BB, Salter JM, Best CH (1960) Glucagon and metaglucagon diabetes in rabbits. Diabetes 9: 278–282

    PubMed  CAS  Google Scholar 

  • Lopez LC, Frazier ML, Su C, Kumar A, Saunders GF (1983) Mammalian pancreatic preproglucagon contains three glucagon-related peptides. Proc Natl Acad Sci USA 80: 5485–5489

    Article  PubMed  CAS  Google Scholar 

  • Lund PK, Goodman RH, Dee PC, Habener JF (1982) Pancreatic preproglucagon cDNA contains two glucagon-related coding sequences arranged in tandem. Proc Natl Acad Sci USA 79: 345–349

    Article  PubMed  CAS  Google Scholar 

  • Lund PK, Goodman RH, Montminy MR, Dee PC, Habener JF (1983) Anglerfish islet preproglucagon II. Nucleotide and corresponding amino-acid sequence of the cDNA. J Biol Chem 258: 3280–3284

    PubMed  CAS  Google Scholar 

  • Mayo KE, Vale W, Rivier J, Rosenfeld MG, Evans RM (1983) Expression-cloning and sequence of a cDNA encoding human growth hormone-releasing factor. Nature 306: 86–88

    Article  PubMed  CAS  Google Scholar 

  • Mayo KE, Cerelli GM, Rosenfeld MG, Evans RM (1985) Gene encoding human growth hormone releasing factor precursor: structure, sequence and chromosomal assignment. Proc Natl Acad Sci USA 82: 63–67

    Article  PubMed  CAS  Google Scholar 

  • Miller CP, Lin JC, Habener JF (1993) Transcription of the rat glucagon gene by the cyclic AMP response element-binding protein CREB is modulated by adjacent CREB-associated proteins. Mol Cell Biol 13: 7080–7090

    PubMed  CAS  Google Scholar 

  • Mojsov S, Heinrich G, Wilson IB, Ravazzola M, Orci L, Habener JF (1986) Preproglucagon gene expression in pancreas and intestine diversifies at the level of post-translational processing. J Biol Chem 261: 11880–11889

    PubMed  CAS  Google Scholar 

  • Morel C, Cordier-Bussat M, Philippe J (1995) The upstream promoter element of the glucagon gene, Gl, confers pancreatic alpha cell-specific expression. J Biol Chem 270: 3046–3055

    Article  PubMed  CAS  Google Scholar 

  • Nishi M, Steiner DF (1990) Cloning of complementary DNAs encoding islet amyloid polypeptide, insulin, and glucagon precursors from a new world rodent, the degu, Octodon degus. Mol Endocrinol 4: 1192–1198

    Article  PubMed  CAS  Google Scholar 

  • Nishizawa M, Hayakawa Y, Yanaihara N, Okamoto H (1985) Nucleotide sequence divergence and functional constraint in vasoactive intestinal peptide precursor mRNA evolution between human and rat. FEBS Lett 183: 55–59

    Article  PubMed  CAS  Google Scholar 

  • Novak U, Wilks A, Buelln G, McEwen S (1987) Identical mRNA for preproglucagon in pancreas and gut. Eur J Biochem 164: 553–558

    Article  PubMed  CAS  Google Scholar 

  • Ohlsson H, Karlsson K, Edlund T (1993) IPF1, a homeodomain-containing transactivator of the insulin gene. EMBO J 12: 4251–4259

    PubMed  CAS  Google Scholar 

  • Pani L, Overdier DG, Porcella A, Qian X, Lai E, Costa RH (1992) Hepatocyte nuclear factor 3 beta contains two transcriptional activation domains, one of which is novel and conserved with the Drosophila fork head protein. Mol Cell Biol 12: 3723–3732

    PubMed  CAS  Google Scholar 

  • Papachristou DN, Pham K, Zingg HH, Patel YC (1989) Tissue-specific alterations in somatostatin mRNA accumulation in streptozotozotocin-induced diabetes. Diabetes 38: 752–757

    Article  PubMed  CAS  Google Scholar 

  • Peers B, Leonard J, Sharma S, Teitelman G, Montminy MR (1994) Insulin expression in pancreatic islet cells relies on cooperative interactions. Mol Endocrinol 8: 1798–1806

    Article  PubMed  CAS  Google Scholar 

  • Philippe J (1989) Glucagon gene transcription is negatively regulated by insulin in a hamster islet cell line. J Clin Invest 84: 672–677

    Article  PubMed  CAS  Google Scholar 

  • Philippe J (1991a) Insulin regulation of the glucagon gene is mediated by an insulin-responsive DNA element. Proc Natl Acad Sci USA 88: 7224–7227

    Article  PubMed  CAS  Google Scholar 

  • Philippe J (1991b) Structure and pancreatic expression of the insulin and glucagon genes. Endocrinol Rev 12: 252–271

    Article  CAS  Google Scholar 

  • Philippe J (1995) Hepatocyte-nuclear factor 3 beta gene transcripts generate protein isoforms with different transactivation properties on the glucagon gene. Mol Endocrinol 9: 368–374

    Article  PubMed  CAS  Google Scholar 

  • Philippe J, Rochat S (1991) Strict distance requirements for transcriptional activation by two regulatory elements of the glucagon gene. DNA Cell Biol 10: 119–124

    Article  PubMed  CAS  Google Scholar 

  • Philippe J, Drucker DJ, Knepel W, Jepeal L, Misulovin Z, Habener JF (1988) Alpha cell-specific expression of the glucagon gene is conferred to the glucagon promoter element by the interactions of DNA-binding proteins. Mol Cell Biol 8: 4877–4888

    PubMed  CAS  Google Scholar 

  • Philippe J, Morel C, Prezioso VR (1994) Glucagon gene expression is negatively regulated by hepatocyte nuclear factor 3 beta. Mol Cell Biol 14: 3514–3523

    PubMed  CAS  Google Scholar 

  • Philippe J, Morel C, Cordier-Bussat M (1995) Islet-specific proteins interact with the insulin-response element of the glucagon gene. J Biol Chem 270: 3039–3045

    Article  PubMed  CAS  Google Scholar 

  • Qian X, Costa RH (1995) Analysis of hepatocyte nuclear factor 3 beta protein domains required for transcriptional activation and nuclear targeting. Nucleic Acids Res 23: 1184–1191

    Article  PubMed  CAS  Google Scholar 

  • Schwaninger M, Lux G, Blume R, Oetjen E, Hidaka H, Knepel W (1993) Membrane depolarizaton and calcium influx induce glucagon gene transcription in pancreatic islet cells through the cyclic AMP-responsive element. J Biol Chem 268: 5168–5177

    PubMed  CAS  Google Scholar 

  • Seino S, Welsh M, Bell GI, Chan SJ, Steiner DF (1986) Mutations in the guinea pig preproglucagon gene are restricted to a specific portion of the prohormone sequence. FEBS Lett 203: 25–30

    Article  PubMed  CAS  Google Scholar 

  • Teitelman G, Alpert S, Polak JM, Martinez A, Hanahan D (1993) Precursor cells of mouse endocrine pancreas coexpress insulin, glucagon and the neuronal proteins tyrosine hydroxylase and neuropeptide Y, but not pancreatic polypeptide. Development 118: 1031–1039

    PubMed  CAS  Google Scholar 

  • Tricoli JV, Bell GI, Shows TB (1984) The human glucagon gene is located on chromosome 2. Diabetes 33: 200–202

    Article  PubMed  CAS  Google Scholar 

  • Tsukada T, Horovitch SJ, Montminy MR, Mandel G, Goodman RH (1985) Structure of the human vasoactive intestinal polypeptide gene, DNA 4: 293–300

    PubMed  CAS  Google Scholar 

  • Voss JW, Rosenfeld MG (1922) Anterior pituitary development: short tales from dwarf mice. Cell 70: 527–530

    Article  Google Scholar 

  • Wang TC, Brand SJ (1990) Islet cell-specific regulatory domain in the gastrin promoter contains adjacent positive and negative DNA elements. J Biol Chem 265: 8908–8914

    PubMed  CAS  Google Scholar 

  • Wheeler MB, Nishitani J, Buchan AM, Kopin AS, Chey WY, Chang TM, Leiter AB (1992) Identification of a transcriptional enhancer important for enteroendocrine and pancreatic islet cell-specific expression of the secretin gene. Mol Cell Biol 12: 3531–3539

    PubMed  CAS  Google Scholar 

  • White JW, Saunders GF (1986) Structure of the human glucagon gene. Nucleic Acids Res 14: 4719–4730

    Article  PubMed  CAS  Google Scholar 

  • Wright WE (1992) Muscle basic helix-loop-helix proteins and the regulation of myogenesis. Curr Opin Genet Dev 2: 243–248

    Article  PubMed  CAS  Google Scholar 

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  1. J. Philippe
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Editors and Affiliations

  1. Department of Medicine, Centre Hospitalier Universitaire de Liège, B-4000, Liège 1, Belgium

    Pierre J. Lefèbvre M.D., Ph.D., FRCP

  2. Division of Diabetes, Nutrition, and Metabolic Disorders, C.H.U. Sart Tilman, B-4000, Liège 1, Belgium

    Pierre J. Lefèbvre M.D., Ph.D., FRCP

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© 1996 Springer-Verlag Berlin Heidelberg

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Philippe, J. (1996). The Glucagon Gene and Its Expression. In: Lefèbvre, P.J. (eds) Glucagon III. Handbook of Experimental Pharmacology, vol 123. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-61150-6_2

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  • DOI: https://doi.org/10.1007/978-3-642-61150-6_2

  • Publisher Name: Springer, Berlin, Heidelberg

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  • Online ISBN: 978-3-642-61150-6

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