Advanced search

Vol 69, No 5 (2018)
Review paper
Published online: 2018-08-03

open access

View PDF Download PDF file
Page views 8139
Article views/downloads 6287
Get Citation

Connect on Social Media

Connect on Social Media

Chromogranin A and its role in the pathogenesis of diabetes mellitus

Zoltan Herold1, Marton Doleschall2, Annamaria Kovesdi1, Attila Patocs34, Aniko Somogyi1
DOI: 10.5603/EP.a2018.0052
Pubmed: 30074235
Endokrynol Pol 2018;69(5):598-610.

Abstract

Chromogranin A is a member of the granin glycoprotein family that is expressed by the endocrine and neuroendocrine cells of different organs. Intracellularly, chromogranin A contributes to the regulation of secretion and gives several cleavage products after secretion. Some of its cleavage products modify the hormone functions in autocrine and paracrine ways, while the functions of others have not been fully understood yet. Serum chromogranin A level is most prominently used in neuroendocrine tumour diagnostics. In addition, recent studies have suggested that chromogranin A and some of its cleavage products (pancreastatin and WE-14) also play important roles in the pathogenesis of the various forms of diabetes mellitus, but their exact mechanisms still need to be clarified. Higher chromogranin A, pancreastatin, and WE-14 levels have been reported in type 1, type 2, and gestational diabetic patients compared to healthy controls. A notable connection has been inferred through the observation that type 1 diabetes mellitus is not at all or rarely developed in chromogranin A gene-knockout, non-obese diabetic model mice compared to non-knockout, non-obese diabetic mice. Pancreastatin inhibits insulin release in various cell and animal models, and WE-14 serves as an autoantigen for both CD4+ and CD8+ beta cell-destructive diabetogenic T-cell clones in type 1 diabetes. Chromogranin A contributes to the pathogenesis of diabetes mellitus according to the available literature. The current findings facilitate further investigation to unravel the deeper relationships between this glycoprotein and diabetes.

Keywords: chromogranin Adiabetes mellitusdiabetes mellitus type 1diabetes mellitus type 2gestational diabetesmice inbred NODpancreastatinWE-14

Article available in PDF format

View PDF Download PDF file

References

  1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014; 37 Suppl 1: S81–S90.
    CrossRefPubMed
  2. Ogurtsova K, da Rocha Fernandes JD, Huang Y, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017; 128: 40–50.
    CrossRefPubMed
  3. Al-Aissa Z, Hadarits O, Rosta K, et al. [A brief of gestational diabetes mellitus, risk factors and current criteria of diagnosis]. Orv Hetil. 2017; 158(8): 283–290.
    CrossRefPubMed
  4. Paschou SA, Papadopoulou-Marketou N, Chrousos GP, et al. On type 1 diabetes mellitus pathogenesis. Endocr Connect. 2018; 7(1): R38–R46.
    CrossRefPubMed
  5. Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005; 365(9467): 1333–1346.
    CrossRefPubMed
  6. Xie F, Chan JCn, Ma RCw. Precision medicine in diabetes prevention, classification and management. J Diabetes Investig. 2018 [Epub ahead of print].
    CrossRefPubMed
  7. Forouhi NG, Wareham NJ. Epidemiology of diabetes. Medicine (Abingdon). 2014; 42(12): 698–702.
    CrossRefPubMed
  8. Ramachandran A, Snehalatha C, Nanditha A. Classification and Diagnosis of Diabetes. In: Holt RIG, Cockram CS, Flyvbjerg A. ed. Textbook of Diabetes. JohnWiley & Sons Ltd, Chichester 2017: 23–28.
  9. Alshiekh S, Larsson H, Ivarsson SA, et al. Autoimmune Type 1 Diabetes. Textbook of Diabetes. 2016: 143–153.
    CrossRef
  10. Lukács K, Pánczél P, Hosszúfalusi N. [Genetics of type 1 diabetes: present and future]. Orv Hetil. 2017; 158(44): 1731–1740.
    CrossRefPubMed
  11. Stadinski BD, Delong T, Reisdorph N, et al. Chromogranin A is an autoantigen in type 1 diabetes. Nat Immunol. 2010; 11(3): 225–231.
    CrossRefPubMed
  12. Gillespie KM. Type 1 diabetes: pathogenesis and prevention. CMAJ. 2006; 175(2): 165–170.
    CrossRefPubMed
  13. Kis J, Engelmann P, Heyam J, et al. [The possibility of immunological prevention in type 1 diabetes mellitus] [Hungarian]. Lege Artis Medicinæ. 2006; 16: 771–773.
  14. Tsai S, Shameli A, Santamaria P. CD8+ T cells in type 1 diabetes. Adv Immunol. 2008; 100: 79–124.
    CrossRefPubMed
  15. Prasad RB, Groop L. Genetic Architecture of Type 2 Diabetes. In: Holt RIG, Cockram CS, Flyvbjerg A. ed. Textbook of Diabetes. JohnWiley & Sons Ltd, Chichester 2017: 187–204.
  16. Reaven GM, Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988; 37(12): 1595–1607.
    CrossRefPubMed
  17. Ricci G, Pirillo I, Tomassoni D, et al. Metabolic syndrome, hypertension, and nervous system injury: Epidemiological correlates. Clin Exp Hypertens. 2017; 39(1): 8–16.
    CrossRefPubMed
  18. Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus: a review of current trends. Oman Med J. 2012; 27(4): 269–273.
    CrossRefPubMed
  19. Federation ID. IDF Diabetes Atlas, 8th ed. Brussels, Belgium, 2017. International Diabetes Federation. http://www.diabetesatlas.org (November 14, 2017).
  20. Gestational Diabetes Mellitus. Diabetes Care. 2003; 26(Supplement 1): S103–S105.
    CrossRef
  21. Konecki DS, Benedum UM, Gerdes HH, et al. The primary structure of human chromogranin A and pancreastatin. J Biol Chem. 1987 ; 262(35): 17026–17030.
    PubMed
  22. Broedbaek K, Hilsted L. Chromogranin A as biomarker in diabetes. Biomark Med. 2016; 10(11): 1181–1189.
    CrossRefPubMed
  23. Angeletti RH, Hickey WF. A neuroendocrine marker in tissues of the immune system. Science. 1985; 230(4721): 89–90.
    PubMed
  24. Nolan JA, Trojanowski JQ, Hogue-Angeletti R. Neurons and neuroendocrine cells contain chromogranin: detection of the molecule in normal bovine tissues by immunochemical and immunohistochemical methods. J Histochem Cytochem. 1985; 33(8): 791–798.
    CrossRefPubMed
  25. Louthan O. Chromogranin a in physiology and oncology. Folia Biol (Praha). 2011; 57(5): 173–181.
    PubMed
  26. Nobels FR, Kwekkeboom DJ, Bouillon R, et al. Chromogranin A: its clinical value as marker of neuroendocrine tumours. Eur J Clin Invest. 1998; 28(6): 431–440.
    PubMed
  27. Taupenot L, Harper KL, O'Connor DT. The chromogranin-secretogranin family. N Engl J Med. 2003; 348(12): 1134–1149.
    CrossRefPubMed
  28. Vinik AI, Silva MP, Woltering EA, et al. Biochemical testing for neuroendocrine tumors. Pancreas. 2009; 38(8): 876–889.
    CrossRefPubMed
  29. Wassberg E, Stridsberg M, Christofferson R. Plasma levels of chromogranin A are directly proportional to tumour burden in neuroblastoma. J Endocrinol. 1996; 151(2): 225–230.
    PubMed
  30. Eriksson B, Öberg K, Stridsberg M. Tumor Markers in Neuroendocrine Tumors. Digestion. 2000; 62(1): 33–38.
    CrossRef
  31. Telega A, Kos-Kudła B, Foltyn W, et al. Selected neuroendocrine tumour markers, growth factors and their receptors in typical and atypical bronchopulmonary carcinoids. Endokrynol Pol. 2012; 63(6): 477–482.
    PubMed
  32. Woliński K, Kaznowski J, Klimowicz A, et al. Diagnostic value of selected biochemical markers in the detection of recurrence of medullary thyroid cancer - comparison of calcitonin, procalcitonin, chromogranin A, and carcinoembryonic antigen. Endokrynol Pol. 2017; 68(4): 434–437.
    CrossRefPubMed
  33. Marotta V, Zatelli MC, Sciammarella C, et al. Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame. Endocr Relat Cancer. 2018; 25(1): R11–R29.
    CrossRefPubMed
  34. Guillemot J, Guérin M, Thouënnon E, et al. Characterization and plasma measurement of the WE-14 peptide in patients with pheochromocytoma. PLoS One. 2014; 9(2): e88698.
    CrossRefPubMed
  35. Blaschko H, Comline RS, Schneider FH, et al. Secretion of a chromaffin granule protein, chromogranin, from the adrenal gland after splanchnic stimulation. Nature. 1967; 215(5096): 58–59.
    CrossRefPubMed
  36. Banks P, Helle K. The release of protein from the stimulated adrenal medulla. Biochem J. 1965; 97(3): 40C–41C.
    PubMed
  37. Gut P, Czarnywojtek A, Fischbach J, et al. Chromogranin A - unspecific neuroendocrine marker. Clinical utility and potential diagnostic pitfalls. Arch Med Sci. 2016; 12(1): 1–9.
    CrossRefPubMed
  38. Tatemoto K, Efendić S, Mutt V, et al. Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. Nature. 1986; 324(6096): 476–478.
    CrossRefPubMed
  39. Schmidt WE, Creutzfeldt W. Pancreastatin — a novel regulatory peptide? Acta Oncol. 1991; 30(4): 441–449.
    CrossRefPubMed
  40. Drees B, Hamilton J. Pancreastatin and bovine parathyroid cell secretion. Bone Miner. 1992; 17(3): 335–346.
    CrossRef
  41. Curry WJ, Shaw C, Johnston CF, et al. Isolation and primary structure of a novel chromogranin A-derived peptide, WE-14, from a human midgut carcinoid tumour. FEBS Lett. 1992; 301(3): 319–321.
    CrossRefPubMed
  42. Gleeson CM, Curry WJ, Johnston CF, et al. Occurrence of WE-14 and chromogranin A-derived peptides in tissues of the human and bovine gastro-entero-pancreatic system and in human neuroendocrine neoplasia. J Endocrinol. 1996; 151(3): 409–420.
    CrossRefPubMed
  43. Barkatullah SC, Pogue KM, Depreitere J, et al. Immunohistochemical localization of WE-14 in the developing porcine sympathoadrenal cell lineage. Histochem Cell Biol. 2001; 116(3): 255–262.
    CrossRefPubMed
  44. Mahata SK, O'Connor DT, Mahata M, et al. Novel autocrine feedback control of catecholamine release. A discrete chromogranin a fragment is a noncompetitive nicotinic cholinergic antagonist. J Clin Invest. 1997; 100(6): 1623–1633.
    CrossRefPubMed
  45. Mahata SK, Mahapatra NR, Mahata M, et al. Catecholamine secretory vesicle stimulus-transcription coupling in vivo. Demonstration by a novel transgenic promoter/photoprotein reporter and inhibition of secretion and transcription by the chromogranin A fragment catestatin. J Biol Chem. 2003; 278(34): 32058–32067.
    CrossRefPubMed
  46. Modi WS, Levine MA, Seuanez HN, et al. The human chromogranin A gene: chromosome assignment and RFLP analysis. Am J Hum Genet. 1989; 45(5): 814–818.
    PubMed
  47. Mouland AJ, Bevan S, White JH, et al. Human chromogranin A gene. Molecular cloning, structural analysis, and neuroendocrine cell-specific expression. J Biol Chem. 1994; 269(9): 6918–6926.
    PubMed
  48. Murray SS, Deaven LL, Burton DW, et al. The gene for human chromogranin A (CgA) is located on chromosome 14. Biochem Biophys Res Commun. 1987; 142(1): 141–146.
    PubMed
  49. Simon JP, Aunis D. Biochemistry of the chromogranin A protein family. Biochem J. 1989; 262(1): 1–13.
    CrossRefPubMed
  50. Reiffen FU, Gratzl M. Chromogranins, widespread in endocrine and nervous tissue, bind Ca2+. FEBS Lett. 1986; 195(1-2): 327–330.
    PubMed
  51. Videen JS, Mezger MS, Chang YM, et al. Calcium and catecholamine interactions with adrenal chromogranins. Comparison of driving forces in binding and aggregation. J Biol Chem. 1992; 267(5): 3066–3073.
    PubMed
  52. Helle K, Metz-Boutigue M, Aunis D. Chromogranin A as a Calcium-Binding Precursor for a Multitude of Regulatory Peptides for the Immune, Endocrine and Metabolic Systems. Current Medicinal Chemistry-Immunology, Endocrine & Metabolic Agents. 2001; 1(2): 119–140.
    CrossRef
  53. Wu HJ, Rozansky DJ, Parmer RJ, et al. Structure and function of the chromogranin A gene. Clues to evolution and tissue-specific expression. J Biol Chem. 1991; 266(20): 13130–13134.
    PubMed
  54. Hendy GN, Bevan S, Mattei MG, et al. Chromogranin A. Clin Invest Med. 1995; 18(1): 47–65.
    PubMed
  55. Benedum UM, Baeuerle PA, Konecki DS, et al. The primary structure of bovine chromogranin A: a representative of a class of acidic secretory proteins common to a variety of peptidergic cells. EMBO J. 1986; 5(7): 1495–1502.
    PubMed
  56. Parmer RJ, Koop AH, Handa MT, et al. Molecular cloning of chromogranin A from rat pheochromocytoma cells. Hypertension. 1989; 14(4): 435–444.
    PubMed
  57. Montero-Hadjadje M, Vaingankar S, Elias S, et al. Chromogranins A and B and secretogranin II: evolutionary and functional aspects. Acta Physiol (Oxf). 2008; 192(2): 309–324.
    CrossRefPubMed
  58. Winkler H, Fischer-Colbrie R. The chromogranins A and B: the first 25 years and future perspectives. Neuroscience. 1992; 49(3): 497–528.
    CrossRefPubMed
  59. Facer P, Bishop AE, Cole GA, et al. Developmental profile of chromogranin, hormonal peptides, and 5-hydroxytryptamine in gastrointestinal endocrine cells. Gastroenterology. 1989; 97(1): 48–57.
    PubMed
  60. Helman LJ, Ahn TG, Levine MA, et al. Molecular cloning and primary structure of human chromogranin A (secretory protein I) cDNA. J Biol Chem. 1988; 263(23): 11559–11563.
    PubMed
  61. Molenaar WM, Lee VM, Trojanowski JQ. Early fetal acquisition of the chromaffin and neuronal immunophenotype by human adrenal medullary cells. An immunohistological study using monoclonal antibodies to chromogranin A, synaptophysin, tyrosine hydroxylase, and neuronal cytoskeletal proteins. Exp Neurol. 1990; 108(1): 1–9.
    PubMed
  62. Banks P, Helle KB, Mayor D. Evidence for the presence of a chromogranin-like protein in bovine splenic nerve granules. Mol Pharmacol. 1969; 5(2): 210–212.
    PubMed
  63. Buffa R, Gini A, Pelagi M, et al. Immunoreactivity of hormonally-characterized human endocrine cells against three novel anti-human chromogranin B(B11 and B13) and chromogranin A (A11) monoclonal antibodies. Arch Histol Cytol. 1989; 52 Suppl: 99–105.
    PubMed
  64. Lauweryns JM, van Ranst L, Lloyd RV, et al. Chromogranin in bronchopulmonary neuroendocrine cells. Immunocytochemical detection in human, monkey, and pig respiratory mucosa. J Histochem Cytochem. 1987; 35(1): 113–118.
    CrossRefPubMed
  65. Helle KB, Corti A, Metz-Boutigue MH, et al. The endocrine role for chromogranin A: a prohormone for peptides with regulatory properties. Cell Mol Life Sci. 2007; 64(22): 2863–2886.
    CrossRefPubMed
  66. Saruta J, Tsukinoki K, Sasaguri K, et al. Expression and localization of chromogranin A gene and protein in human submandibular gland. Cells Tissues Organs. 2005; 180(4): 237–244.
    CrossRefPubMed
  67. Cramer T, Jüttner S, Plath T, et al. Gastrin transactivates the chromogranin A gene through MEK-1/ERK- and PKC-dependent phosphorylation of Sp1 and CREB. Cell Signal. 2008; 20(1): 60–72.
    CrossRefPubMed
  68. Mahapatra NR, Mahata M, O'Connor DT, et al. Secretin activation of chromogranin A gene transcription. Identification of the signaling pathways in cis and in trans. J Biol Chem. 2003; 278(22): 19986–19994.
    CrossRefPubMed
  69. Anouar Y, Benie T, De Monti M, et al. Estradiol negatively regulates secretogranin II and chromogranin A messenger ribonucleic acid levels in the female rat pituitary but not in the adrenal. Endocrinology. 1991; 129(5): 2393–2399.
    CrossRefPubMed
  70. Anouar Y, Duval J. Direct estradiol down-regulation of secretogranin II and chromogranin A mRNA levels in rat pituitary cells. Mol Cell Endocrinol. 1992; 88(1-3): 97–104.
    PubMed
  71. Takiyyuddin MA, Neumann HP, Cervenka JH, et al. Ultradian variations of chromogranin A in humans. Am J Physiol. 1991; 261(4 Pt 2): R939–R944.
    CrossRefPubMed
  72. Galindo E, Bader MF, Aunis D. Regulation of chromogranin a and chromogranin B (secretogranin I) synthesis in bovine cultured chromaffin cells. J Neuroendocrinol. 1991; 3(6): 669–677.
    CrossRefPubMed
  73. Simon JP, Bader MF, Aunis D. Effect of secretagogues on chromogranin A synthesis in bovine cultured chromaffin cells. Possible regulation by protein kinase C. Biochem J. 1989; 260(3): 915–922.
    CrossRefPubMed
  74. Kim T, Tao-Cheng JH, Eiden LE, et al. Chromogranin A, an "on/off" switch controlling dense-core secretory granule biogenesis. Cell. 2001; 106(4): 499–509.
    PubMed
  75. Gorr SU, Dean WL, Radley TL, et al. Calcium-binding and aggregation properties of parathyroid secretory protein-I (chromogranin A). Bone Miner. 1988; 4(1): 17–25.
    PubMed
  76. Yoo SH, Lewis MS. Effects of pH and Ca2+ on monomer-dimer and monomer-tetramer equilibria of chromogranin A. J Biol Chem. 1992; 267(16): 11236–11241.
    PubMed
  77. Settleman J, Nolan J, Angeletti RH. Chromogranin, an integral membrane protein. J Biol Chem. 1985; 260(3): 1641–1644.
    PubMed
  78. Westermann R, Stögbauer F, Unsicker K, et al. Calcium-dependence of chromogranin A-catecholamine interaction. FEBS Lett. 1988; 239(2): 203–206.
    PubMed
  79. Gorr SU, Shioi J, Cohn DV. Interaction of calcium with porcine adrenal chromogranin A (secretory protein-I) and chromogranin B (secretogranin I). Am J Physiol. 1989; 257(2 Pt 1): E247–E254.
    CrossRefPubMed
  80. Seidah NG, Hendy GN, Hamelin J, et al. Chromogranin A can act as a reversible processing enzyme inhibitor. Evidence from the inhibition of the IRCM-serine protease 1 cleavage of pro-enkephalin and ACTH at pairs of basic amino acids. FEBS Lett. 1987; 211(2): 144–150.
    CrossRefPubMed
  81. Huttner WB, Natori S. Regulated secretion. Helper proteins for neuroendocrine secretion. Curr Biol. 1995; 5(3): 242–245.
    PubMed
  82. Kiang WL, Krusius T, Finne J, et al. Glycoproteins and proteoglycans of the chromaffin granule matrix. J Biol Chem. 1982; 257(4): 1651–1659.
    PubMed
  83. Bhargava G, Russell J, Sherwood LM. Phosphorylation of parathyroid secretory protein. Proc Natl Acad Sci U S A. 1983; 80(3): 878–881.
    PubMed
  84. Gorr SU, Hamilton JW, Cohn DV, et al. Secretion of sulfated and nonsulfated forms of parathyroid chromogranin A (secretory protein-I). J Biol Chem. 1990; 265(6): 3012–3016.
    PubMed
  85. Nguyen MH, Harbour D, Gagnon C. Secretory proteins from adrenal medullary cells are carboxyl-methylated in vivo and released under their methylated form by acetylcholine. J Neurochem. 1987; 49(1): 38–44.
    PubMed
  86. Sigafoos J, Chestnut WG, Merrill BM, et al. Novel peptides from adrenomedullary chromaffin vesicles. J Anat. 1993; 183 ( Pt 2): 253–264.
    PubMed
  87. Eskeland NL, Zhou A, Dinh TQ, et al. Chromogranin A processing and secretion: specific role of endogenous and exogenous prohormone convertases in the regulated secretory pathway. J Clin Invest. 1996; 98(1): 148–156.
    CrossRefPubMed
  88. Biswas N, Rodriguez-Flores JL, Courel M, et al. Cathepsin L colocalizes with chromogranin a in chromaffin vesicles to generate active peptides. Endocrinology. 2009; 150(8): 3547–3557.
    CrossRefPubMed
  89. Hook V, Yasothornsrikul S, Greenbaum D, et al. Cathepsin L and Arg/Lys aminopeptidase: a distinct prohormone processing pathway for the biosynthesis of peptide neurotransmitters and hormones. Biol Chem. 2004; 385(6): 473–480.
    CrossRefPubMed
  90. Benedum UM, Lamouroux A, Konecki DS, et al. The primary structure of human secretogranin I (chromogranin B): comparison with chromogranin A reveals homologous terminal domains and a large intervening variable region. EMBO J. 1987; 6(5): 1203–1211.
    PubMed
  91. Thiele C, Huttner WB. The disulfide-bonded loop of chromogranins, which is essential for sorting to secretory granules, mediates homodimerization. J Biol Chem. 1998; 273(2): 1223–1231.
    PubMed
  92. Rouillé Y, Duguay SJ, Lund K, et al. Proteolytic processing mechanisms in the biosynthesis of neuroendocrine peptides: the subtilisin-like proprotein convertases. Front Neuroendocrinol. 1995; 16(4): 322–361.
    CrossRefPubMed
  93. Prigge ST, Mains RE, Eipper BA, et al. New insights into copper monooxygenases and peptide amidation: structure, mechanism and function. Cell Mol Life Sci. 2000; 57(8-9): 1236–1259.
    PubMed
  94. Metz-Boutigue MH, Garcia-Sablone P, Hogue-Angeletti R, et al. Intracellular and extracellular processing of chromogranin A. Determination of cleavage sites. Eur J Biochem. 1993; 217(1): 247–257.
    PubMed
  95. Jiang Q, Taupenot L, Mahata SK, et al. Proteolytic cleavage of chromogranin A (CgA) by plasmin. Selective liberation of a specific bioactive CgA fragment that regulates catecholamine release. J Biol Chem. 2001; 276(27): 25022–25029.
    CrossRefPubMed
  96. Parmer RJ, Mahata M, Gong Y, et al. Processing of chromogranin A by plasmin provides a novel mechanism for regulating catecholamine secretion. J Clin Invest. 2000; 106(7): 907–915.
    CrossRefPubMed
  97. Crippa L, Bianco M, Colombo B, et al. A new chromogranin A-dependent angiogenic switch activated by thrombin. Blood. 2013; 121(2): 392–402.
    CrossRefPubMed
  98. Curry WJ, Johnston CF, Hutton JC, et al. The tissue distribution of rat chromogranin A-derived peptides: evidence for differential tissue processing from sequence specific antisera. Histochemistry. 1991; 96(6): 531–538.
    PubMed
  99. Portela-Gomes GM, Stridsberg M. Selective processing of chromogranin A in the different islet cells in human pancreas. J Histochem Cytochem. 2001; 49(4): 483–490.
    CrossRefPubMed
  100. Portela-Gomes GM, Stridsberg M. Chromogranin A in the human gastrointestinal tract: an immunocytochemical study with region-specific antibodies. J Histochem Cytochem. 2002; 50(11): 1487–1492.
    CrossRefPubMed
  101. Baker RL, Bradley B, Wiles TA, et al. Cutting Edge: Nonobese Diabetic Mice Deficient in Chromogranin A Are Protected from Autoimmune Diabetes. J Immunol. 2016; 196(1): 39–43.
    CrossRefPubMed
  102. Li Yi, Zhou L, Li Y, et al. Identification of autoreactive CD8+ T cell responses targeting chromogranin A in humanized NOD mice and type 1 diabetes patients. Clin Immunol. 2015; 159(1): 63–71.
    CrossRefPubMed
  103. Anderson MS, Venanzi ES, Klein L, et al. Projection of an immunological self shadow within the thymus by the aire protein. Science. 2002; 298(5597): 1395–1401.
    CrossRefPubMed
  104. Delong T, Baker RL, He J, et al. Diabetogenic T-cell clones recognize an altered peptide of chromogranin A. Diabetes. 2012; 61(12): 3239–3246.
    CrossRefPubMed
  105. Gottlieb PA, Delong T, Baker RL, et al. Chromogranin A is a T cell antigen in human type 1 diabetes. J Autoimmun. 2014; 50: 38–41.
    CrossRefPubMed
  106. Jin N, Wang Y, Crawford F, et al. N-terminal additions to the WE14 peptide of chromogranin A create strong autoantigen agonists in type 1 diabetes. Proc Natl Acad Sci U S A. 2015; 112(43): 13318–13323.
    CrossRefPubMed
  107. Sollid L. Molecular Basis of Celiac Disease. Annu Rev Immunol. 2000; 18(1): 53–81.
    CrossRef
  108. Blancou P, Mallone R, Martinuzzi E, et al. Immunization of HLA class I transgenic mice identifies autoantigenic epitopes eliciting dominant responses in type 1 diabetes patients. J Immunol. 2007; 178(11): 7458–7466.
    PubMed
  109. Serreze DV, Marron MP, Dilorenzo TP. "Humanized" HLA transgenic NOD mice to identify pancreatic beta cell autoantigens of potential clinical relevance to type 1 diabetes. Ann N Y Acad Sci. 2007; 1103: 103–111.
    CrossRefPubMed
  110. Takaki T, Marron MP, Mathews CE, et al. HLA-A*0201-restricted T cells from humanized NOD mice recognize autoantigens of potential clinical relevance to type 1 diabetes. J Immunol. 2006; 176(5): 3257–3265.
    PubMed
  111. Kogawa EM, Grisi DC, Falcão DP, et al. Impact of glycemic control on oral health status in type 2 diabetes individuals and its association with salivary and plasma levels of chromogranin A. Arch Oral Biol. 2016; 62: 10–19.
    CrossRefPubMed
  112. Kogawa EM, Grisi DC, Falcão DP, et al. Salivary function impairment in type 2 Diabetes patients associated with concentration and genetic polymorphisms of chromogranin A. Clin Oral Investig. 2016; 20(8): 2083–2095.
    CrossRefPubMed
  113. Mahapatra NR, O'Connor DT, Vaingankar SM, et al. Hypertension from targeted ablation of chromogranin A can be rescued by the human ortholog. J Clin Invest. 2005; 115(7): 1942–1952.
    CrossRefPubMed
  114. Gayen JR, Saberi M, Schenk S, et al. A novel pathway of insulin sensitivity in chromogranin A null mice: a crucial role for pancreastatin in glucose homeostasis. J Biol Chem. 2009; 284(42): 28498–28509.
    CrossRefPubMed
  115. Tang K, Pasqua T, Biswas A, et al. Muscle injury, impaired muscle function and insulin resistance in Chromogranin A-knockout mice. J Endocrinol. 2017; 232(2): 137–153.
    CrossRefPubMed
  116. Bandyopadhyay GK, Vu CU, Gentile S, et al. Catestatin (chromogranin A(352-372)) and novel effects on mobilization of fat from adipose tissue through regulation of adrenergic and leptin signaling. J Biol Chem. 2012; 287(27): 23141–23151.
    CrossRefPubMed
  117. González-Yanes C, Sánchez-Margalet V. Pancreastatin, a chromogranin A-derived peptide, inhibits leptin and enhances UCP-2 expression in isolated rat adipocytes. Cell Mol Life Sci. 2003; 60(12): 2749–2756.
    CrossRefPubMed
  118. Sánchez V, Lucas M, Calvo JR, et al. Glycogenolytic effect of pancreastatin in isolated rat hepatocytes is mediated by a cyclic-AMP-independent Ca(2+)-dependent mechanism. Biochem J. 1992; 284 ( Pt 3): 659–662.
    CrossRefPubMed
  119. Ahrén B, Bertrand G, Roye M, et al. Pancreastatin modulates glucose-stimulated insulin secretion from the perfused rat pancreas. Acta Physiol Scand. 1996; 158(1): 63–70.
    CrossRefPubMed
  120. Sanchez V, Calvo JR, Goberna R. Glycogenolytic effect of pancreastatin in the rat. Biosci Rep. 1990; 10(1): 87–91.
    CrossRefPubMed
  121. Sánchez-Margalet V, González-Yanes C, Najib S, et al. Metabolic effects and mechanism of action of the chromogranin A-derived peptide pancreastatin. Regul Pept. 2010; 161(1-3): 8–14.
    CrossRefPubMed
  122. Valicherla GR, Hossain Z, Mahata SK, et al. Pancreastatin is an endogenous peptide that regulates glucose homeostasis. Physiol Genomics. 2013; 45(22): 1060–1071.
    CrossRefPubMed
  123. Mosén H, Salehi A, Henningsson R, et al. Nitric oxide inhibits, and carbon monoxide activates, islet acid alpha-glucoside hydrolase activities in parallel with glucose-stimulated insulin secretion. J Endocrinol. 2006; 190(3): 681–693.
    CrossRefPubMed
  124. Sánchez-Margalet V, González-Yanes C, Najib S. Pancreastatin, a chromogranin A-derived peptide, inhibits DNA and protein synthesis by producing nitric oxide in HTC rat hepatoma cells. J Hepatol. 2001; 35(1): 80–85.
    CrossRefPubMed
  125. Tateishi K, Funakoshi A, Wakasugi H, et al. Plasma pancreastatin-like immunoreactivity in various diseases. J Clin Endocrinol Metab. 1989; 69(6): 1305–1308.
    CrossRefPubMed
  126. Funakoshi A, Tateishi K, Shinozaki H, et al. Elevated plasma levels of pancreastatin (PST) in patients with non-insulin-dependent diabetes mellitus (NIDDM). Regul Pept. 1990; 30(2): 159–164.
    CrossRefPubMed
  127. O'Connor DT, Cadman PE, Smiley C, et al. Pancreastatin: multiple actions on human intermediary metabolism in vivo, variation in disease, and naturally occurring functional genetic polymorphism. J Clin Endocrinol Metab. 2005; 90(9): 5414–5425.
    CrossRefPubMed
  128. Sánchez-Margalet V, Valle M, Lobón JA, et al. Increased plasma pancreastatin-like immunoreactivity levels in non-obese patients with essential hypertension. J Hypertens. 1995; 13(2): 251–258.
    CrossRefPubMed
  129. Sánchez-Margalet V, Lobón JA, González A, et al. Increased plasma pancreastatin-like levels in gestational diabetes: correlation with catecholamine levels. Diabetes Care. 1998; 21(11): 1951–1954.
    CrossRefPubMed
  130. Ying W, Mahata S, Bandyopadhyay GK, et al. Chromogranin A Regulation of Obesity and Peripheral Insulin Sensitivity. Front Endocrinol (Lausanne). 2017; 8(5): 20–848.
    CrossRefPubMed
  131. Kim SJ, Tang T, Abbott M, et al. AMPK Phosphorylates Desnutrin/ATGL and Hormone-Sensitive Lipase To Regulate Lipolysis and Fatty Acid Oxidation within Adipose Tissue. Mol Cell Biol. 2016; 36(14): 1961–1976.
    CrossRefPubMed
  132. Gayen JR, Gu Y, O'Connor DT, et al. Global disturbances in autonomic function yield cardiovascular instability and hypertension in the chromogranin a null mouse. Endocrinology. 2009; 150(11): 5027–5035.
    CrossRefPubMed
  133. Ying W, Mahata S, Bandyopadhyay GK, et al. Catestatin Inhibits Obesity-Induced Macrophage Infiltration and Inflammation in the Liver and Suppresses Hepatic Glucose Production, Leading to Improved Insulin Sensitivity. Diabetes. 2018; 67(5): 841–848.
    CrossRefPubMed
  134. Degorce F, Goumon Y, Jacquemart L, et al. A new human chromogranin A (CgA) immunoradiometric assay involving monoclonal antibodies raised against the unprocessed central domain (145-245). Br J Cancer. 1999; 79(1): 65–71.
    CrossRefPubMed
  135. Stridsberg M, Eriksson B, Oberg K, et al. A comparison between three commercial kits for chromogranin A measurements. J Endocrinol. 2003; 177(2): 337–341.
    PubMed
  136. Soell M, Feki A, Hannig M, et al. Chromogranin A detection in saliva of type 2 diabetes patients. Bosn J Basic Med Sci. 2010; 10(1): 2–8.
    CrossRefPubMed
  137. Stridsberg M. Measurements of chromogranins and chromogranin-related peptides by immunological methods. Adv Exp Med Biol. 2000; 482: 319–327.
    CrossRefPubMed
  138. Pregun I, Herszényi L, Juhász M, et al. Effect of proton-pump inhibitor therapy on serum chromogranin a level. Digestion. 2011; 84(1): 22–28.
    CrossRefPubMed
  139. Glinicki P, Jeske W. Chromogranin A (CgA) — the influence of various factors in vivo and in vitro, and existing disorders on it's concentration in blood. Endokrynol Pol. 2010; 61(4): 384–387.
    PubMed
  140. Goetze JP, Alehagen U, Flyvbjerg A, et al. Chromogranin A as a biomarker in cardiovascular disease. Biomark Med. 2014; 8(1): 133–140.
    CrossRefPubMed
  141. Kollipara S. Comorbidities associated with type 1 diabetes. School Nurse News. 2006; 23(4): 42–45.
    PubMed
  142. Glinicki P, Jeske W, Kapuścińska R, et al. Comparison of chromogranin A (CgA) levels in serum and plasma (EDTA2K) and the respective reference ranges in healthy males. Endokrynol Pol. 2015; 66(1): 53–56.
    CrossRefPubMed
  143. Glinicki P, Kapuścińska R, Jeske W. The differences in chromogranin A (CgA) concentrations measured in serum and in plasma by IRMA and ELISA methods. Endokrynol Pol. 2010; 61(4): 346–350.
    PubMed
  144. Tsao KC, Wu JT. Development of an ELISA for the detection of serum chromogranin A (CgA) in prostate and non-neuroendocrine carcinomas. Clin Chim Acta. 2001; 313(1-2): 21–29.
    PubMed
  145. Popovici T, Moreira B, Schlageter MH, et al. Automated two-site immunofluorescent assay for the measurement of serum chromogranin A. Clin Biochem. 2014; 47(1-2): 87–91.
    CrossRefPubMed
  146. van der Knaap RHP, Kwekkeboom DJ, Ramakers CRB, et al. Evaluation of a new immunoassay for chromogranin A measurement on the Kryptor system. Pract Lab Med. 2015; 1: 5–11.
    CrossRefPubMed
  147. Ferrero S, Buffa R, Pruneri G, et al. The prevalence and clinical significance of chromogranin A and secretogranin II immunoreactivity in colorectal adenocarcinomas. Virchows Arch. 1995; 426(6): 587–592.
    PubMed
  148. Huegel R, Velasco P, De la Luz Sierra M, et al. Novel anti-inflammatory properties of the angiogenesis inhibitor vasostatin. J Invest Dermatol. 2007; 127(1): 65–74.
    CrossRefPubMed
  149. Xiong W, Wang X, Dai D, et al. The anti-inflammatory vasostatin-2 attenuates atherosclerosis in ApoE mice and inhibits monocyte/macrophage recruitment. Thromb Haemost. 2017; 117(2): 401–414.
    CrossRefPubMed
  150. Lugardon K, Raffner R, Goumon Y, et al. Antibacterial and antifungal activities of vasostatin-1, the N-terminal fragment of chromogranin A. J Biol Chem. 2000; 275(15): 10745–10753.
    PubMed
  151. Helle KB, Metz-Boutigue MH, Cerra MC, et al. Chromogranins: from discovery to current times. Pflugers Arch. 2018; 470(1): 143–154.
    CrossRefPubMed
  152. Aardal S, Helle KB. The vasoinhibitory activity of bovine chromogranin A fragment (vasostatin) and its independence of extracellular calcium in isolated segments of human blood vessels. Regul Pept. 1992; 41(1): 9–18.
    CrossRefPubMed
  153. Drees BM, Rouse J, Johnson J, et al. Bovine parathyroid glands secrete a 26-kDa N-terminal fragment of chromogranin-A which inhibits parathyroid cell secretion. Endocrinology. 1991; 129(6): 3381–3387.
    CrossRefPubMed
  154. Lugardon K, Chasserot-Golaz S, Kieffer AE, et al. Structural and biological characterization of chromofungin, the antifungal chromogranin A-(47-66)-derived peptide. J Biol Chem. 2001; 276(38): 35875–35882.
    CrossRefPubMed
  155. Zhang D, Shooshtarizadeh P, Laventie BJ, et al. Two chromogranin a-derived peptides induce calcium entry in human neutrophils by calmodulin-regulated calcium independent phospholipase A2. PLoS One. 2009; 4(2): e4501.
    CrossRefPubMed
  156. Salem S, Jankowski V, Asare Y, et al. Identification of the Vasoconstriction-Inhibiting Factor (VIF), a Potent Endogenous Cofactor of Angiotensin II Acting on the Angiotensin II Type 2 Receptor. Circulation. 2015; 131(16): 1426–1434.
    CrossRefPubMed
  157. Galindo E, Rill A, Bader MF, et al. Chromostatin, a 20-amino acid peptide derived from chromogranin A, inhibits chromaffin cell secretion. Proc Natl Acad Sci U S A. 1991; 88(4): 1426–1430.
    CrossRefPubMed
  158. Strub JM, Goumon Y, Lugardon K, et al. Antibacterial activity of glycosylated and phosphorylated chromogranin A-derived peptide 173-194 from bovine adrenal medullary chromaffin granules. J Biol Chem. 1996; 271(45): 28533–28540.
    PubMed
  159. Gayen JR, Zhang K, RamachandraRao SP, et al. Role of reactive oxygen species in hyperadrenergic hypertension: biochemical, physiological, and pharmacological evidence from targeted ablation of the chromogranin a (Chga) gene. Circ Cardiovasc Genet. 2010; 3(5): 414–425.
    CrossRefPubMed
  160. Bandyopadhyay GK, Lu M, Avolio E, et al. Pancreastatin-dependent inflammatory signaling mediates obesity-induced insulin resistance. Diabetes. 2015; 64(1): 104–116.
    CrossRefPubMed
  161. Cadman PE, Rao F, Mahata SK, et al. Studies of the dysglycemic peptide, pancreastatin, using a human forearm model. Ann N Y Acad Sci. 2002; 971: 528–529.
    PubMed
  162. Aslam R, Marban C, Corazzol C, et al. Cateslytin, a chromogranin A derived peptide is active against Staphylococcus aureus and resistant to degradation by its proteases. PLoS One. 2013; 8(7): e68993.
    CrossRefPubMed
  163. Zaet A, Dartevelle P, Daouad F, et al. D-Cateslytin, a new antimicrobial peptide with therapeutic potential. Sci Rep. 2017; 7(1): 15199.
    CrossRefPubMed
  164. Briolat J, Wu SD, Mahata SK, et al. New antimicrobial activity for the catecholamine release-inhibitory peptide from chromogranin A. Cell Mol Life Sci. 2005; 62(3): 377–385.
    CrossRefPubMed
  165. O'Connor DT, Kailasam MT, Kennedy BP, et al. Early decline in the catecholamine release-inhibitory peptide catestatin in humans at genetic risk of hypertension. J Hypertens. 2002; 20(7): 1335–1345.
    PubMed
  166. Angelone T, Quintieri AM, Brar BK, et al. The antihypertensive chromogranin a peptide catestatin acts as a novel endocrine/paracrine modulator of cardiac inotropism and lusitropism. Endocrinology. 2008; 149(10): 4780–4793.
    CrossRefPubMed
  167. Bassino E, Fornero S, Gallo MP, et al. A novel catestatin-induced antiadrenergic mechanism triggered by the endothelial PI3K-eNOS pathway in the myocardium. Cardiovasc Res. 2011; 91(4): 617–624.
    CrossRefPubMed
  168. Theurl M, Schgoer W, Albrecht K, et al. The neuropeptide catestatin acts as a novel angiogenic cytokine via a basic fibroblast growth factor-dependent mechanism. Circ Res. 2010; 107(11): 1326–1335.
    CrossRefPubMed
  169. Mohseni S, Emtenani S, Emtenani S, et al. Antioxidant properties of a human neuropeptide and its protective effect on free radical-induced DNA damage. J Pept Sci. 2014; 20(6): 429–437.
    CrossRefPubMed
  170. Fasciotto BH, Denny JC, Greeley GH, et al. Processing of chromogranin A in the parathyroid: generation of parastatin-related peptides. Peptides. 2000; 21(9): 1389–1401.
    PubMed
  171. Fasciotto BH, Trauss CA, Greeley GH, et al. Parastatin (porcine chromogranin A347-419), a novel chromogranin A-derived peptide, inhibits parathyroid cell secretion. Endocrinology. 1993; 133(2): 461–466.
    CrossRefPubMed
  172. Kirchmair R, Leitner B, Fischer-Colbrie R, et al. Large variations in the proteolytic formation of a chromogranin A-derived peptide (GE-25) in neuroendocrine tissues. Biochem J. 1995; 310 ( Pt 1): 331–336.
    PubMed
  173. Lorenz K, Gramlich OW, Grus FH, et al. GE-25-like immunoreactivity in the rat eye. Peptides. 2012; 36(2): 286–291.
    CrossRefPubMed
  174. Loh YP, Koshimizu H, Cawley NX, et al. Serpinins: role in granule biogenesis, inhibition of cell death and cardiac function. Curr Med Chem. 2012; 19(24): 4086–4092.
    PubMed
  175. Tota B, Gentile S, Pasqua T, et al. The novel chromogranin A-derived serpinin and pyroglutaminated serpinin peptides are positive cardiac β-adrenergic-like inotropes. FASEB J. 2012; 26(7): 2888–2898.
    CrossRefPubMed

About cookies

Necessary cookies

Allways active

These cookies are necessary for the proper display and operation of the website. Blocking them may cause the website to malfunction.

Analytical cookies

As part of our website, we use analytical tools, such as Google Analytics, that allow us to verify website traffic. These tools may require the use of cookies.

Community cookies

These are cookies associated with the social networks we use. Accepting them will allow us to associate your visit to the site with our social media profiles.

Marketing cookies

These are cookies responsible for carrying out advertising and marketing activities - consenting to their use will allow us to target you with advertisements based on your previous activities within our website.

Copyright © 2023-2024 Via Medica Regulations Cookie policy Privacy Statement Legal Note