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Biogenesis of the Insulin Secretory Granule in Health and Disease

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Reviews on Biomarker Studies of Metabolic and Metabolism-Related Disorders

Part of the book series: Advances in Experimental Medicine and Biology ((PMISB,volume 1134))

Abstract

The secretory granules of pancreatic beta cells are specialized organelles responsible for the packaging, storage and secretion of the vital hormone insulin. The insulin secretory granules also contain more than 100 other proteins including the proteases involved in proinsulin-to insulin conversion, other precursor proteins, minor co-secreted peptides, membrane proteins involved in cell trafficking and ion translocation proteins essential for regulation of the intragranular environment. The synthesis, transport and packaging of these proteins into nascent granules must be carried out in a co-ordinated manner to ensure correct functioning of the granule. The process is regulated by many circulating nutrients such as glucose and can change under different physiological states. This chapter discusses the various processes involved in insulin granule biogenesis with a focus on the granule composition in health and disease.

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References

  1. Michael J, Carroll R, Swift HH, Steiner DF (1987) Studies on the molecular organization of rat insulin secretory granules. J Biol Chem 262(34):16531–16535

    CAS  PubMed  Google Scholar 

  2. Barg S, Eliasson L, Renström E, Rorsman P (2002) A subset of 50 secretory granules in close contact with L-type Ca2+ channels accounts for first-phase insulin secretion in mouse beta-cells. Diabetes 51(Suppl 1):S74–S82

    Article  CAS  PubMed  Google Scholar 

  3. Olofsson CS, Gopel SO, Barg S, Galvanovskis J, Ma X, Salehi A et al (2002) Fast insulin secretion reflects exocytosis of docked granules in mouse pancreatic B-cells. Pflugers Arch 444:43–51

    Article  CAS  PubMed  Google Scholar 

  4. Hutton JC (1989) The insulin secretory granule. Diabetologia 32(5):271–281

    Article  CAS  PubMed  Google Scholar 

  5. Hutton JC, Penn EJ, Peshavaria M (1983) Low-molecular-weight constituents of isolated insulin-secretory granules. Bivalent cations, adenine nucleotides and inorganic phosphate. Biochem J 210(2):297–305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Davidson HW, Peshavaria M, Hutton JC (1987) Proteolytic conversion of proinsulin into insulin. Identification of a Ca2+-dependent acidic endopeptidase in isolated insulin-secretory granules. Biochem J 246(2):279–286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hutton JC, Penn EJ, Peshavaria M (1982) Isolation and characterisation of insulin secretory granules from a rat islet cell tumour. Diabetologia 23(4):365–373

    Article  CAS  PubMed  Google Scholar 

  8. Guest PC, Bailyes EM, Rutherford NG, Hutton JC (1991) Insulin secretory granule biogenesis. Co-ordinate regulation of the biosynthesis of the majority of constituent proteins. Biochem J 274(Pt 1):73–78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Brunner Y, Couté Y, Iezzi M, Foti M, Fukuda M, Hochstrasser DF et al (2007) Proteomics analysis of insulin secretory granules. Mol Cell Proteomics 6(6):1007–1017

    Article  CAS  PubMed  Google Scholar 

  10. Schvartz D, Brunner Y, Couté Y, Foti M, Wollheim CB, Sanchez JC (2012) Improved characterization of the insulin secretory granule proteomes. J Proteomics 75:4620–4631

    Article  CAS  PubMed  Google Scholar 

  11. Cerasi E (1967) An analogue computer model for the insulin response to glucose infusion. Acta Endocrinol 55(1):163–183

    Article  CAS  Google Scholar 

  12. Turner RC, Schneeloch B, Nabarro JD (1972) Biphasic insulin secretory response to intravenous xylitol and glucose in normal, diabetic and obese subjects. J Clin Endocrinol Metab 33(2):301–307

    Article  Google Scholar 

  13. Bratanova-Tochkova TK, Cheng H, Daniel S, Gunawardana S, Liu YJ, Mulvaney-Musa J et al (2002) Triggering and augmentation mechanisms, granule pools, and biphasic insulin secretion. Diabetes 51(Suppl 1):S83–S90

    Article  CAS  PubMed  Google Scholar 

  14. Kahn SE, Montgomery B, Howell W, Ligueros-Saylan M, Hsu CH, Devineni D et al (2001) Importance of early phase insulin secretion to intravenous glucose tolerance in subjects with type 2 diabetes mellitus. J Clin Endocrinol Metab 86:5824–5829

    Article  CAS  PubMed  Google Scholar 

  15. Mako ME, Starr JI, Rubenstein AH (1977) Circulating proinsulin in patients with maturity onset diabetes. Am J Med 63(6):865–869

    Article  CAS  PubMed  Google Scholar 

  16. Guest PC, Abdel-Halim SM, Gross DJ, Clark A, Poitout V, Amaria R et al (2002) Proinsulin processing in the diabetic Goto-Kakizaki rat. J Endocrinol 175(3):637–647

    Article  CAS  PubMed  Google Scholar 

  17. Poitout V, Robertson RP (2008) Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev 29:351–366

    Article  CAS  PubMed  Google Scholar 

  18. Poitout V, Hagman D, Stein R, Artner I, Robertson RP, Harmon JS (2006) Regulation of the insulin gene by glucose and fatty acids. J Nutr 136(4):873–876

    Article  CAS  PubMed  Google Scholar 

  19. Giddings SJ, Chirgwin J, Permutt MA (1982) Effects of glucose on proinsulin messenger RNA in rats in vivo. Diabetes 31(7):624–629

    Article  CAS  PubMed  Google Scholar 

  20. Welsh M, Nielsen DA, MacKrell AJ, Steiner DF (1985) Control of insulin gene expression in pancreatic beta-cells and in an insulin-producing cell line, RIN-5F cells. II. Regulation of insulin mRNA stability. J Biol Chem 260(25):13590–13594

    CAS  PubMed  Google Scholar 

  21. Fu Z, Gilbert ER, Liu D (2013) Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr Diabetes Rev 9(1):25–53

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hutton JC, Guest PC, Rhodes CJ, Fricker LD, Grimaldi KA, Siddle K et al (1989) Biogenesis of the insulin secretion granule. Journ Annu Diabetol Hotel Dieu 1989:13–28

    Google Scholar 

  23. Guest PC, Rhodes CJ, Hutton JC (1989) Regulation of the biosynthesis of insulin-secretory-granule proteins. Co-ordinate translational control is exerted on some, but not all, granule matrix constituents. Biochem J 257(2):431–437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Egea PF, Stroud RM, Walter P (2005) Targeting proteins to membranes: structure of the signal recognition particle. Curr Opin Struct Biol 15(2):213–220

    Article  CAS  PubMed  Google Scholar 

  25. Patzelt C, Labrecque AD, Duguid JR, Carroll RJ, Keim PS, Heinrikson RL et al (1978) Detection and kinetic behavior of preproinsulin in pancreatic islets. Proc Natl Acad Sci U S A 75(3):1260–1264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liu M, Sun J, Cui J, Chen W, Guo H, Barbetti F et al (2015) INS-gene mutations: from genetics and beta cell biology to clinical disease. Mol Asp Med 42:3–18

    Article  CAS  Google Scholar 

  27. Kahn CR, Weir GC (2005) Joslin’s diabetes mellitus, 14th edn. Lippincott Williams & Wilkins, Philadelphia. ISBN 978-8493531836

    Google Scholar 

  28. Orci L, Ravazzola M, Storch MJ, Anderson RG, Vassalli JD, Perrelet A (1987) Proteolytic maturation of insulin is a post-Golgi event which occurs in acidifying clathrin-coated secretory vesicles. Cell 49(6):865–868

    Article  CAS  PubMed  Google Scholar 

  29. Davidson HW, Rhodes CJ, Hutton JC (1988) Intraorganellar calcium and pH control proinsulin cleavage in the pancreatic beta cell via two distinct site-specific endopeptidases. Nature 333(6168):93–96

    Article  CAS  PubMed  Google Scholar 

  30. Halban PA (1994) Proinsulin processing in the regulated and the constitutive secretory pathway. Diabetologia 37(Suppl 2):S65–S72

    Article  CAS  PubMed  Google Scholar 

  31. Kahn SE, Halban PA (1997) Release of incompletely processed proinsulin is the cause of the disproportionate proinsulinemia of NIDDM. Diabetes 46(11):1725–1732

    Article  CAS  PubMed  Google Scholar 

  32. Boland BB, Rhodes CJ, Grimsby JS (2017) The dynamic plasticity of insulin production in β-cells. Mol Metab 6(9):958–973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lithaw PN (ed) (2009) Glycolysis: regulation, processes & diseases (Biochemistry research trends). Nova Science Publishers Inc, Hauppauge; UK ed. ISBN-10: 1607411032

    Google Scholar 

  34. Daniel S, Noda M, Straub SG, Sharp GW (1999) Identification of the docked granule pool responsible for the first phase of glucose-stimulated insulin secretion. Diabetes 48:1686–1690

    Article  CAS  PubMed  Google Scholar 

  35. Gromada J, Hoy M, Renstrom E, Bokvist K, Eliasson L, Gopel S (1999) CaM kinase II-dependent mobilization of secretory granules underlies acetylcholine-induced stimulation of exocytosis in mouse pancreatic B-cells. J Physiol 518:745–759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Renstrom E, Eliasson L, Rorsman P (1997) Protein kinase A-dependent and -independent stimulation of exocytosis by cAMP in mouse pancreatic B-cells. J Physiol 502:105–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Henquin JC, Ishiyama N, Nenquin M, Ravier MA, Jonas JC (2002) Signals and pools underlying biphasic insulin secretion. Diabetes 51(Suppl 1):S60–S67

    Article  CAS  PubMed  Google Scholar 

  38. Rorsman P, Renstrom E (2003) Insulin granule dynamics in pancreatic beta cells. Diabetologia 46:1029–1045

    Article  CAS  PubMed  Google Scholar 

  39. Schvartz D, Brunner Y, Couté Y, Foti M, Wollheim CB, Sanchez JC (2012) Improved characterization of the insulin secretory granule proteomes. J Proteome 75(15):4620–4631

    Article  CAS  Google Scholar 

  40. Konecki DS, Benedum UM, Gerdes HH, Huttner WB (1987) The primary structure of human chromogranin A and pancreastatin. J Biol Chem 262(35):17026–11730

    CAS  PubMed  Google Scholar 

  41. O’Connor DT, Bernstein KN (1984) Radioimmunoassay of chromogranin A in plasma as a measure of exocytotic sympathoadrenal activity in normal subjects and patients with pheochromocytoma. N Engl J Med 311(12):764–770

    Article  PubMed  Google Scholar 

  42. Varndell IM, Lloyd RV, Wilson BS, Polak JM (1985) Ultrastructural localization of chromogranin: a potential marker for the electron microscopical recognition of endocrine cell secretory granules. Histochem J 17(9):981–992

    Article  CAS  PubMed  Google Scholar 

  43. Di Giacinto P, Rota F, Rizza L, Campana D, Isidori A, Lania A et al (2018) Chromogranin A: from laboratory to clinical aspects of patients with neuroendocrine tumors. Int J Endocrinol 2018:8126087. https://doi.org/10.1155/2018/8126087

    Article  PubMed  PubMed Central  Google Scholar 

  44. Soell M, Feki A, Hannig M, Sano H, Pinget M, Selimovic D (2010) Chromogranin A detection in saliva of type 2 diabetes patients. Bosn J Basic Med Sci 10(1):2–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Broedbaek K, Hilsted L (2016) Chromogranin A as biomarker in diabetes. Biomark Med 10(11):1181–1189

    Article  CAS  PubMed  Google Scholar 

  46. Goetze JP, Alehagen U, Flyvbjerg A, Rehfeld JF (2014) Chromogranin A as a biomarker in cardiovascular disease. Biomark Med 8(1):133–140

    Article  CAS  PubMed  Google Scholar 

  47. Aardal S, Helle KB (1992) The vasoinhibitory activity of bovine chromogranin A fragment (vasostatin) and its independence of extracellular calcium in isolated segments of human blood vessels. Regul Pept 41(1):9–18

    Article  CAS  PubMed  Google Scholar 

  48. Tatemoto K, Efendic S, Mutt V, Makk G, Feistner GJ, Barchas JD (1986) Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion. Nature 324(6096):476–478

    Article  CAS  PubMed  Google Scholar 

  49. Curry WJ, Shaw C, Johnston CF, Thim L, Buchanan KD (1992) Isolation and primary structure of a novel chromogranin A-derived peptide, WE-14, from a human midgut carcinoid tumour. FEBS Lett 301(3):319–321

    Article  CAS  PubMed  Google Scholar 

  50. Mahata SK, O’Connor DT, Mahata M, Yoo SH, Taupenot L, Wu H et al (1997) Novel autocrine feedback control of catecholamine release. A discrete chromogranin A fragment is a noncompetitive nicotinic cholinergic antagonist. J Clin Invest 100(6):1623–1633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Koshimizu H, Cawley NX, Kim T, Yergey AL, Loh YP (2011) Serpinin: a novel chromogranin A-derived, secreted peptide up-regulates protease nexin-1 expression and granule biogenesis in endocrine cells. Mol Endocrinol 25:732–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Crippa L, Bianco M, Colombo B, Gasparri AM, Ferrero E, Loh YP et al (2013) A new chromogranin A-dependent angiogenic switch activated by thrombin. Blood 121(2):392–402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bandyopadhyay GK, Mahata SK (2017) Chromogranin A regulation of obesity and peripheral insulin sensitivity. Front Endocrinol (Lausanne) 2017(8):20. https://doi.org/10.3389/fendo.2017.00020

    Article  Google Scholar 

  54. Curry WJ, Johnston CF, Hutton JC, Arden SD, Rutherford NG, Shaw C et al (1991) The tissue distribution of rat chromogranin A-derived peptides: evidence for differential tissue processing from sequence specific antisera. Histochemistry 96(6):531–538

    Article  CAS  PubMed  Google Scholar 

  55. Watkinson A, Jönsson AC, Davison M, Young J, Lee CM, Moore S et al (1991) Heterogeneity of chromogranin A-derived peptides in bovine gut, pancreas and adrenal medulla. Biochem J 276(Pt 2):471–479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Arden SD, Rutherford NG, Guest PC, Curry WJ, Bailyes EM, Johnston CF et al (1994) The post-translational processing of chromogranin A in the pancreatic islet: involvement of the eukaryote subtilisin PC2. Biochem J 298(Pt 3):521–528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hutton JC, Davidson HW, Grimaldi KA, Peshavaria M (1987) Biosynthesis of betagranin in pancreatic beta-cells. Identification of a chromogranin A-like precursor and its parallel processing with proinsulin. Biochem J 244(2):449–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Seidah NG, Gaspar L, Mion P, Marcinkiewicz M, Mbikay M, Chrétien M (1990) cDNA sequence of two distinct pituitary proteins homologous to Kex2 and furin gene products: tissue-specific mRNAs encoding candidates for pro-hormone processing proteinases. DNA Cell Biol 9(6):415–424

    Article  CAS  PubMed  Google Scholar 

  59. Smeekens SP, Steiner DF (1990) Identification of a human insulinoma cDNA encoding a novel mammalian protein structurally related to the yeast dibasic processing protease Kex2. J Biol Chem 265(6):2997–3000

    CAS  PubMed  Google Scholar 

  60. Seidah NG, Chrétien M (1992) Proprotein and prohormone convertases of the subtilisin family recent developments and future perspectives. Trends Endocrinol Metab 3(4):133–140

    Article  CAS  PubMed  Google Scholar 

  61. Steiner DF (1998) The proprotein convertases. Curr Opin Chem Biol 2(1):31–39

    Article  CAS  PubMed  Google Scholar 

  62. Vindrola O, Lindberg I (1992) Biosynthesis of the prohormone convertase mPC1 in AtT-20 cells. Mol Endocrinol 6(7):1088–1094

    CAS  PubMed  Google Scholar 

  63. Benjannet S, Rondeau N, Paquet L, Boudreault A, Lazure C, Chrétien M et al (1993) Comparative biosynthesis, covalent post-translational modifications and efficiency of prosegment cleavage of the prohormone convertases PC1 and PC2: glycosylation, sulphation and identification of the intracellular site of prosegment cleavage of PC1 and PC2. Biochem J 294(Pt 3):735–743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lee SN, Prodhomme E, Lindberg I (2004) Prohormone convertase 1 (PC1) processing and sorting: effect of PC1 propeptide and proSAAS. J Endocrinol 182(2):353–364

    Article  CAS  PubMed  Google Scholar 

  65. Rhodes CJ, Alarcon C (1994) What beta-cell defect could lead to hyperproinsulinemia in NIDDM? Some clues from recent advances made in understanding the proinsulin-processing mechanism. Diabetes 43:511–517

    Article  CAS  PubMed  Google Scholar 

  66. Katsuta H, Ozawa S, Suzuki K, Takahashi K, Tanaka T, Sumitani Y et al (2015) The association between impaired proinsulin processing and type 2 diabetes mellitus in non-obese Japanese individuals. Endocr J 62(6):485–492

    Article  CAS  PubMed  Google Scholar 

  67. Zhu X, Orci L, Carroll R, Norrbom C, Ravazzola M, Steiner DF (2002) Severe block in processing of proinsulin to insulin accompanied by elevation of des-64,65 proinsulin intermediates in islets of mice lacking prohormone convertase 1/3. Proc Natl Acad Sci U S A 99(16):10299–10304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Podlecki DA, Frank BH, Olefsky JM (1984) In vitro characterization of biosynthetic human proinsulin. Diabetes 33(2):111–118

    Article  CAS  PubMed  Google Scholar 

  69. Jackson RS, Creemers JW, Ohagi S, Raffin-Sanson ML, Sanders L, Montague CT et al (1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 16:303–306

    Article  CAS  PubMed  Google Scholar 

  70. Jackson RS, Creemers JW, Farooqi IS, Raffin-Sanson ML, Varro A, Dockray GJ et al (2003) Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J Clin Invest 112:1550–1560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Farooqi IS, Volders K, Stanhope R, Heuschkel R, White A, Lank E et al (2007) Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. J Clin Endocrinol Metab 92:3369–3337

    Article  CAS  PubMed  Google Scholar 

  72. Bennett DL, Bailyes EM, Nielsen E, Guest PC, Rutherford NG, Arden SD et al (1992) Identification of the type 2 proinsulin processing endopeptidase as PC2, a member of the eukaryote subtilisin family. J Biol Chem 267(21):15229–15236

    CAS  PubMed  Google Scholar 

  73. Guest PC, Arden SD, Bennett DL, Clark A, Rutherford NG, Hutton JC (1992) The post-translational processing and intracellular sorting of PC2 in the islets of Langerhans. J Biol Chem 267(31):22401–22406

    CAS  PubMed  Google Scholar 

  74. Furuta M, Carroll R, Martin S, Swift HH, Ravazzola M, Orci L et al (1998) Incomplete processing of proinsulin to insulin accompanied by elevation of Des-31,32 proinsulin intermediates in islets of mice lacking active PC2. J Biol Chem 273(6):3431–3437

    Article  CAS  PubMed  Google Scholar 

  75. Docherty K, Hutton JC (1983) Carboxypeptidase activity in the insulin secretory granule. FEBS Lett 162(1):137–141

    Article  CAS  PubMed  Google Scholar 

  76. Davidson HW, Hutton JC (1987) The insulin-secretory-granule carboxypeptidase H. Purification and demonstration of involvement in proinsulin processing. Biochem J 245(2):575–582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Guest PC, Arden SD, Rutherford NG, Hutton JC (1995) The post-translational processing and intracellular sorting of carboxypeptidase H in the islets of Langerhans. Mol Cell Endocrinol 113(1):99–108

    Article  CAS  PubMed  Google Scholar 

  78. Naggert JK, Fricker LD, Varlamov O, Nishina PM, Rouille Y, Steiner DF et al (1995) Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity. Nat Genet 10(2):135–142

    Article  CAS  PubMed  Google Scholar 

  79. Rodriguiz RM, Wilkins JJ, Creson TK, Biswas R, Berezniuk I, Fricker AD et al (2013) Emergence of anxiety-like behaviours in depressive-like Cpe(fat/fat) mice. Int J Neuropsychopharmacol 16(7):1623–1634

    Article  CAS  PubMed  Google Scholar 

  80. Ji L, Wu HT, Qin XY, Lan R (2017) Dissecting carboxypeptidase E: properties, functions and pathophysiological roles in disease. Endocr Connect 6(4):R18–R38

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Li P, Tiwari HK, Lin WY, Allison DB, Chung WK, Leibel RL et al (2014) Genetic association analysis of 30 genes related to obesity in a European American population. Int J Obes 38(5):724–729

    Article  CAS  Google Scholar 

  82. Hickey AJ, Bradley JW, Skea GL, Middleditch MJ, Buchanan CM, Phillips AR et al (2009) Proteins associated with immunopurified granules from a model pancreatic islet beta-cell system: proteomic snapshot of an endocrine secretory granule. J Proteome Res 8(1):178–186

    Article  CAS  PubMed  Google Scholar 

  83. Smith LF (1966) Species variation in the amino acid sequence of insulin. Am J Med 40(5):662–666

    Article  CAS  PubMed  Google Scholar 

  84. Troger J, Theurl M, Kirchmair R, Pasqua T, Tota B, Angelone T et al (2017) Granin-derived peptides. Prog Neurobiol 154:37–61

    Article  CAS  PubMed  Google Scholar 

  85. Bradbury AF, Smyth DG (1991) Peptide amidation. Trends Biochem Sci 16(3):112–115

    Article  CAS  PubMed  Google Scholar 

  86. Strbák V, Dutour A, Nikodémová M, Oliver C (1994) Pancreastatin-like immunoreactivity in the pancreas of newborn rats. Horm Metab Res 26(4):173–174

    Article  PubMed  Google Scholar 

  87. Johnson KH, O’Brien TD, Hayden DW, Jordan K, Ghobrial HK, Mahoney WC et al (1988) Immunolocalization of islet amyloid polypeptide (IAPP) in pancreatic beta cells by means of peroxidase-antiperoxidase (PAP) and protein A-gold techniques. Am J Pathol 130(1):1–8

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Wasmeier C, Hutton JC (1996) Molecular cloning of phogrin, a protein-tyrosine phosphatase homologue localized to insulin secretory granule membranes. J Biol Chem 271(30):18161–18170

    Article  CAS  PubMed  Google Scholar 

  89. Höög A, Hu W, Abdel-Halim SM, Falkmer S, Qing L, Grimelius L (1997) Ultrastructural localization of insulin-like growth factor-2 (IGF-2) to the secretory granules of insulin cells: a study in normal and diabetic (GK) rats. Ultrastruct Pathol 21(5):457–466

    Article  PubMed  Google Scholar 

  90. Ohara-Imaizumi M, Nishiwaki C, Kikuta T, Nagai S, Nakamichi Y, Nagamatsu S (2004) TIRF imaging of docking and fusion of single insulin granule motion in primary rat pancreatic beta-cells: different behavior of granule motion between normal and Goto-Kakizaki diabetic rat beta-cells. Biochem J 381:13–18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Kwan EP, Gaisano HY (2009) Rescuing the subprime meltdown in insulin exocytosis in diabetes. Ann NYAcad Sci 1152:154–164

    Article  CAS  Google Scholar 

  92. Zhu D, Xie L, Karimian N, Liang T, Kang Y, Huang YC et al (2015) Munc18c mediates exocytosis of pre-docked and newcomer insulin granules underlying biphasic glucose stimulated insulin secretion in human pancreatic beta-cells. Mol Metab 4(5):418–426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Liang T, Qin T, Xie L, Dolai S, Zhu D, Prentice KJ et al (2017) New roles of syntaxin-1A in insulin granule exocytosis and replenishment. J Biol Chem 292(6):2203–2216

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil

    Paul C. Guest

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    Paul C. Guest

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Guest, P.C. (2019). Biogenesis of the Insulin Secretory Granule in Health and Disease. In: Guest, P. (eds) Reviews on Biomarker Studies of Metabolic and Metabolism-Related Disorders. Advances in Experimental Medicine and Biology(), vol 1134. Springer, Cham. https://doi.org/10.1007/978-3-030-12668-1_2

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