Skip to main content

Advertisement

SpringerLink
Log in

VMAT2 gene expression and function as it applies to imaging β-cell mass

  • Review
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia. The two main forms of the disease are distinguished by different pathogenesis, natural histories, and population distributions and indicated as either type 1 (T1DM) or type 2 diabetes mellitus (T2DM). It is well established that T1DM is an autoimmune disease whereby β-cells of pancreatic islets are destroyed leading to loss of endogenous insulin production. Albeit less dramatic, β-cell mass (BCM) also drops in T2DM. Therefore, it is realistic to expect that noninvasive measures of BCM might provide useful information in the diabetes-care field. Preclinical studies have demonstrated that BCM measurements by positron emission tomography scanning, using the vesicular monoamine transporter type 2 (VMAT2) as a tissue-specific surrogate marker of insulin production and [11C] Dihydrotetrabenazine (DTBZ) as the radioligand specific for this molecule, is feasible in animal models. Unfortunately, the mechanisms underlying β-cell-specific expression of VMAT2 are still largely unexplored, and a much better understanding of the regulation of VMAT2 gene expression and of its function in β-cells will be required before the full utility of this technique in the prediction and treatment of individuals with diabetes can be understood. In this review, we summarize much of what is understood about the regulation of VMAT2 and identify questions whose answers may help in understanding what measurements of VMAT2 density mean in the context of diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Lohr M, Kloppel G (1987) Residual insulin positivity and pancreatic atrophy in relation to duration of chronic type 1 (insulin-dependent) diabetes mellitus and microangiopathy. Diabetologia 30:757–62

    PubMed  CAS  Google Scholar 

  2. Sosenko JM, Palmer JP, Greenbaum CJ, Mahon J, Cowie C, Krischer JP, Chase HP, White NH, Buckingham B, Herold KC, Cuthbertson D, Skyler JS (2006) Patterns of metabolic progression to type 1 diabetes in the diabetes prevention trial-type 1. Diabetes Care 29:643–649

    PubMed  Google Scholar 

  3. McCulloch DK, Koerker DJ, Kahn SE, Bonner-Weir S, Palmer JP (1991) Correlations of in vivo beta-cell function tests with beta-cell mass and pancreatic insulin content in streptozocin-administered baboons. Diabetes 40:673–679

    PubMed  CAS  Google Scholar 

  4. Kjems LL, Kirby BM, Welsh EM, Veldhuis JD, Straume M, McIntyre SS, Yang D, Lefebvre P, Butler PC (2001) Decrease in beta-cell mass leads to impaired pulsatile insulin secretion, reduced postprandial hepatic insulin clearance, and relative hyperglucagonemia in the minipig. Diabetes 50:2001–2012

    PubMed  CAS  Google Scholar 

  5. Larsen MO, Gotfredsen CF, Wilken M, Carr RD, Porksen N, Rolin B (2003) Loss of beta-cell mass leads to a reduction of pulse mass with normal periodicity, regularity and entrainment of pulsatile insulin secretion in Gottingen minipigs. Diabetologia 46:195–202

    PubMed  CAS  Google Scholar 

  6. Larsen MO, Rolin B(2004) Use of the Gottingen minipig as a model of diabetes, with special focus on type 1 diabetes research. ILAR J 45:303–313

    PubMed  CAS  Google Scholar 

  7. Greenbaum CJ (2002) Type 1 diabetes intervention trials: what have we learned? A critical review of selected intervention trials. Clin Immunol 104:97–104

    PubMed  CAS  Google Scholar 

  8. Orland MJ, Chyn R, Permutt MA (1985) Modulation of proinsulin messenger RNA after partial pancreatectomy in rats. Relationships to glucose homeostasis. J Clin Invest 75:2047–2055

    PubMed  CAS  Google Scholar 

  9. Evgenov NV, Medarova Z, Dai G, Bonner-Weir S, Moore A (2006) In vivo imaging of islet transplantation. Nat Med 12:144–148

    PubMed  CAS  Google Scholar 

  10. Kim SJ, Doudet DJ, Studenov AR, Nian C, Ruth TJ, Gambhir SS, McIntosh CH (2006) Quantitative micro positron emission tomography (PET) imaging for the in vivo determination of pancreatic islet graft survival. Nat Med 12:1423–1428

    PubMed  CAS  Google Scholar 

  11. Souza F, Freeby M, Hultman K, Simpson N, Herron A, Witkowsky P, Liu E, Maffei A, Harris PE (2006) Current progress in non-invasive imaging of beta cell mass of the endocrine pancreas. Curr Med Chem 13:2761–2773

    PubMed  CAS  Google Scholar 

  12. Simpson NR, Souza F, Witkowski P, Maffei A, Raffo A, Herron A, Kilbourn M, Jurewicz A, Herold K, Liu E, Hardy MA, Van Heertum R, Harris PE (2006) Visualizing pancreatic beta-cell mass with [11C]DTBZ. Nucl Med Biol 33:855–864

    PubMed  CAS  Google Scholar 

  13. Souza F, Simpson N, Raffo A, Saxena C, Maffei A, Hardy M, Kilbourn M, Goland R, Leibel R, Mann JJ, Van Heertum R, Harris PE (2006) Longitudinal noninvasive PET-based beta cell mass estimates in a spontaneous diabetes rat model. J Clin Invest 116:1506–1513

    PubMed  CAS  Google Scholar 

  14. Frey KA, Koeppe RA, Kilbourn MR (2001) Imaging the vesicular monoamine transporter. Adv Neurol 86:237–247

    PubMed  CAS  Google Scholar 

  15. Anlauf M, Eissele R, Schafer MK, Eiden LE, Arnold R, Pauser U, Kloppel G, Weihe E (2003) Expression of the two isoforms of the vesicular monoamine transporter (VMAT1 and VMAT2) in the endocrine pancreas and pancreatic endocrine tumors. J Histochem Cytochem 51:1027–1040

    PubMed  CAS  Google Scholar 

  16. Weihe E, Schafer MK, Erickson JD, Eiden LE (1994) Localization of vesicular monoamine transporter isoforms (VMAT1 and VMAT2) to endocrine cells and neurons in rat. J Mol Neurosci 5:149–164

    PubMed  CAS  Google Scholar 

  17. Maffei A, Liu Z, Witkowski P, Moschella F, Del Pozzo G, Liu E, Herold K, Winchester RJ, Hardy MA, Harris PE (2004) Identification of tissue-restricted transcripts in human islets. Endocrinology 145:4513–4521

    PubMed  CAS  Google Scholar 

  18. Weihe E, Eiden LE (2000) Chemical neuroanatomy of the vesicular amine transporters. FASEB J 14:2435–2449

    PubMed  CAS  Google Scholar 

  19. Anlauf M, Schafer MKH, Schwark T, von Wurmb-Schwark N, Brand V, Sipos B, Horny H-P, Parwaresch R, Hartschuh W, Eiden LE, Kloppel G, Weihe E (2006) Vesicular Monoamine Transporter 2 (VMAT2) Expression in Hematopoietic Cells and in Patients with Systemic Mastocytosis. J Histochem Cytochem 54:201–213

    PubMed  CAS  Google Scholar 

  20. Eiden LE (2000) The vesicular neurotransmitter transporters: current perspectives and future prospects. FASEB J 14:2396–2400

    PubMed  CAS  Google Scholar 

  21. Erickson JD, Schafer MKH, Bonner TI, Eiden LE, Weihe E (1996) Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter. Proc Natl Acad Sci USA 93:5166–5171

    PubMed  CAS  Google Scholar 

  22. Fon EA, Pothos EN, Sun BC, Killeen N, Sulzer D, Edwards RH (1997) Vesicular transport regulates monoamine storage and release but is not essential for amphetamine action. Neuron 19:1271–1283

    PubMed  CAS  Google Scholar 

  23. Peter D, Liu Y, Sternini C, de Giorgio R, Brecha N, Edwards RH (1995) Differential expression of two vesicular monoamine transporters. J Neurosci 15:6179–6188

    PubMed  CAS  Google Scholar 

  24. Mezey E, Eisenhofer G, Harta G, Hansson S, Gould L, Hunyady B, Hoffman BJ (1996) A novel nonneuronal catecholaminergic system: exocrine pancreas synthesizes and releases dopamine. Proc Natl Acad Sci USA 93:10377–10382

    PubMed  CAS  Google Scholar 

  25. Anlauf M, Schafer MKH, Depboylu C, Hartschuh W, Eiden LE, Kloppel G, Weihe E (2004) The Vesicular Monoamine Transporter 2 (VMAT2) is expressed by normal and tumor cutaneous mast cells and langerhans cells of the skin but is absent from langerhans cell histiocytosis. J Histochem Cytochem 52:779–788

    PubMed  CAS  Google Scholar 

  26. Uccella S, Cerutti R, Vigetti D, Furlan D, Oldrini R, Carnevali I, Pelosi G, La Rosa S, Passi A, Capella C (2006) Histidine decarboxylase, DOPA decarboxylase, and vesicular monoamine transporter 2 expression in neuroendocrine tumors: immunohistochemical study and gene expression analysis. J Histochem Cytochem 54:863–875

    PubMed  CAS  Google Scholar 

  27. Rindi G, Paolotti D, Fiocca R, Wiedenmann B, Henry JP, Solcia E (2000) Vesicular monoamine transporter 2 as a marker of gastric enterochromaffin-like cell tumors. Virchows Arch 436:217–223

    PubMed  CAS  Google Scholar 

  28. Tanimoto A, Matsuki Y, Tomita T, Sasaguri T, Shimajiri S, Sasaguri Y (2004) Histidine decarboxylase expression in pancreatic endocrine cells and related tumors. Pathol Int 54:408–412

    PubMed  CAS  Google Scholar 

  29. Graff L, Frungieri M, Zanner R, Pohlinger A, Prinz C, Gratzl M (2002) Expression of histidine decarboxylase and synthesis of histamine by human small cell lung carcinoma. Am J Pathol 160:1561–1565

    PubMed  CAS  Google Scholar 

  30. Brunk I, Blex C, Rachakonda S, Holtje M, Winter S, Pahner I, Walther DJ, Ahnert-Hilger G (2006) The first luminal domain of vesicular monoamine transporters mediates G-protein-dependent regulation of transmitter uptake. J Biol Chem 281:33373–33385

    PubMed  CAS  Google Scholar 

  31. Brunk I, Holtje M, von Jagow B, Winter S, Sternberg J, Blex C, Pahner I, Ahnert-Hilger G (2006) Regulation of vesicular monoamine and glutamate transporters by vesicle-associated trimeric G proteins: new jobs for long-known signal transduction molecules. Handb Exp Pharmacol 175:305–325

    PubMed  CAS  Google Scholar 

  32. Ahnert-Hilger G, Höltje M, Pahner I, Winter S, Brunk I (2003) Regulation of vesicular neurotransmitter transporters. Rev Physiol Biochem Pharmacol 150:140–160

    PubMed  CAS  Google Scholar 

  33. Pothos EN, Larsen KE, Krantz DE, Liu Y-j, Haycock JW, Setlik W, Gershon MD, Edwards RH, Sulzer D (2000) Synaptic vesicle transporter expression regulates vesicle phenotype and quantal size. J Neurosci 20:7297–7306

    PubMed  CAS  Google Scholar 

  34. Song H, Ming G, Fon E, Bellocchio E, Edwards RH, Poo M (1997) Expression of a putative vesicular acetylcholine transporter facilitates quantal transmitter packaging. Neuron 18:815–826

    PubMed  CAS  Google Scholar 

  35. Travis ER,Wang Y-M, Michael DJ, Caron MG, Wightman RM (2000) Differential quantal release of histamine and 5-hydroxytryptamine from mast cells of vesicular monoamine transporter 2 knockout mice. Proc Natl Acad Sci USA 97:162–167

    PubMed  CAS  Google Scholar 

  36. Wang YM, Gainetdinov RR, Fumagalli F, Xu F, Jones SR, Bock CB, Miller GW, Wightman RM, Caron MG (1997) Knockout of the vesicular monoamine transporter 2 gene results in neonatal death and supersensitivity to cocaine and amphetamine. Neuron 19:1285–1296

    PubMed  CAS  Google Scholar 

  37. Wojcik SM, Rhee JS, Herzog E, Sigler A, Jahn R, Takamori S, Brose N, Rosenmund C (2004) An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size. Proc Natl Acad Sci USA 101:7158–7163

    PubMed  CAS  Google Scholar 

  38. Moechars D, Weston MC, Leo S, Callaerts-Vegh Z, Goris I, Daneels G, Buist A, Cik M, van der Spek P, Kass S, Meert T, D’Hooge R, Rosenmund C, Hampson RM (2006) Vesicular Glutamate Transporter VGLUT2 expression levels control quantal size and neuropathic pain. J Neurosci 26:12055–12066

    PubMed  CAS  Google Scholar 

  39. Takahashi N, Miner LL, Sora I, Ujike H, Revay RS, Kostic V, Jackson-Lewis V, Przedborski S, Uhl GR (1997) VMAT2 knockout mice: heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity. Proc Natl Acad Sci USA 94:9938–9943

    PubMed  CAS  Google Scholar 

  40. Fumagalli F, Gainetdinov RR, Wang Y-M, Valenzano KJ, Miller GW, Caron MG (1999) Increased methamphetamine neurotoxicity in heterozygous vesicular monoamine transporter 2 knock-out mice. J Neurosci 19:2424–2431

    PubMed  CAS  Google Scholar 

  41. Johnson-Davis KL, Truong JG, Fleckenstein AE, Wilkins DG (2004) Alterations in vesicular dopamine uptake contribute to tolerance to the neurotoxic effects of methamphetamine. J Pharmacol Exp Ther 309:578–586

    PubMed  CAS  Google Scholar 

  42. Glatt CE, DeYoung JA, Delgado S, Service SK, Giacomini KM, Edwards RH Risch N, Freimer NB (2001) Screening a large reference sample to identify very low frequency sequence variants: comparisons between two genes. Nat Genet 27:435–438

    PubMed  CAS  Google Scholar 

  43. Burman J, Tran CH, Glatt C, Freimer NB, Edwards RH (2004) The effect of rare human sequence variants on the function of vesicular monoamine transporter 2. Pharmacogenetics 14:587–594

    PubMed  CAS  Google Scholar 

  44. Glatt CE, Wahner AD, White DJ, Ruiz-Linares A, Ritz B (2006) Gain-of-function haplotypes in the vesicular monoamine transporter promoter are protective for Parkinson disease in women. Hum Mol Genet 15:299–305

    PubMed  CAS  Google Scholar 

  45. Lin Z, Walther D, Yu X-Y, Li S, Drgon T, Uhl GR (2005) SLC18A2 promoter haplotypes and identification of a novel protective factor against alcoholism. Hum Mol Genet 14:1393–1404

    PubMed  CAS  Google Scholar 

  46. Albin RL, Koeppe RA, Bohnen NI, Nichols TE, Meyer P, Wernette K, Minoshima S, Kilbourn MR, Frey KA(2003) Increased ventral striatal monoaminergic innervation in Tourette syndrome. Neurology 61:310–315

    PubMed  CAS  Google Scholar 

  47. Frey KA, Koeppe RA, Kilbourn MR,Vander Borght TM, Albin RL, Gilman S, Kuhl DE (1996) Presynaptic monoaminergic vesicles in Parkinson’s disease and normal aging. Ann Neurol 40:873–884

    PubMed  CAS  Google Scholar 

  48. Zubieta JK, Huguelet P, Ohl LE, Koeppe RA, Kilbourn MR, Carr JM, Giordani BJ, Frey KA (2000) High vesicular monoamine transporter binding in asymptomatic bipolar I disorder: sex differences and cognitive correlates. Am J Psychiatry 157:1619–1628

    PubMed  CAS  Google Scholar 

  49. Guardiola J, Maffei A, Lauster R, Mitchison NA, Accolla RS, Sartoris S (1996) Functional significance of polymorphism among MHC class II gene promoters. Tissue Antigens 48:615–625

    Article  PubMed  CAS  Google Scholar 

  50. Maffei A, Harris PE, Reed EF, Del Pozzo G, Ciullo M, Suciu-Foca N, Guardiola J (1997) Differential expression of insulin-dependent diabetes mellitus-associated HLA-DQA1 alleles in vivo. Eur J Immunol 27:1549–1556

    PubMed  CAS  Google Scholar 

  51. Hall FS, Sora I, Uhl GR (2003) Sex-dependent modulation of ethanol consumption in vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) knockout mice. Neuropsychopharmacology 28:620–628

    PubMed  Google Scholar 

  52. Lee CS, Samii A, Sossi V, Ruth TJ, Schulzer M, Holden JE, Wudel J, Pal PK, de la Fuente-Fernandez R, Calne DB, Stoessl AJ (2000) In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson’s disease. Ann Neurol 47:493–503

    PubMed  CAS  Google Scholar 

  53. Miller GW, Erickson JD, Perez JT, Penland SN, Mash DC, Rye DB, Levey AI (1999) Immunochemical analysis of vesicular monoamine transporter (VMAT2) protein in Parkinson’s disease. Exp Neurol 156:138–148

    PubMed  CAS  Google Scholar 

  54. Miller GW, Erickson JD, Perez JT, Penland SN, Mash DC, Rye DB, Levey AI (1999) Immunochemical analysis of vesicular monoamine transporter (VMAT2) protein in Parkinson’s disease. Exp Neurol 156:138–148

    PubMed  CAS  Google Scholar 

  55. Lu W, Wolf ME (1997) Expression of dopamine transporter and vesicular monoamine transporter 2 mRNAs in rat midbrain after repeated amphetamine administration. Brain Res Mol Brain Res 49:137–148

    PubMed  CAS  Google Scholar 

  56. Richardson JR, Miller GW (2004) Acute exposure to aroclor 1016 or 1260 differentially affects dopamine transporter and vesicular monoamine transporter 2 levels. Toxicol Lett 148:29–40

    PubMed  CAS  Google Scholar 

  57. Rusnak M, Kvetnansky R, Jelokova J, Palkovits M (2001) Effect of novel stressors on gene expression of tyrosine hydroxylase and monoamine transporters in brainstem noradrenergic neurons of long-term repeatedly immobilized rats. Brain Res 899:20–35

    PubMed  CAS  Google Scholar 

  58. Jankovic J, Chen S, Le WD (2005) The role of Nurr1 in the development of dopaminergic neurons and Parkinson’s disease. Prog Neurobiol 77:128

    PubMed  CAS  Google Scholar 

  59. Smits SM, Ponnio T, Conneely OM, Burbach JPH, Smidt MP (2003) Involvement of Nurr1 in specifying the neurotransmitter identity of ventral midbrain dopaminergic neurons. Eur J Neurosci 18:1731–1738

    PubMed  Google Scholar 

  60. Watson F, Deavall DG, Macro JA, Kiernan R, Dimaline R (1999) Transcriptional activation of vesicular monoamine transporter 2 in the pre-B cell line Ea3.123. Biochem J 337(Pt 2):193–199

    PubMed  CAS  Google Scholar 

  61. Watson F, Kiernan RS, Deavall DG, Varro A, Dimaline R (2001) Transcriptional activation of the rat vesicular monoamine transporter 2 promoter in gastric epithelial cells. Regulation by gastrin. J Biol Chem 276:7661–7671

    PubMed  CAS  Google Scholar 

  62. Desnos C, Laran M-P, Langley K, Aunis D, Henry J-P (1995) Long term stimulation changes the vesicular monoamine transporter content of chromaffin granules. J Biol Chem 270:16030–16038

    PubMed  CAS  Google Scholar 

  63. Prinz C, Zanner R, Gerhard M, Mahr S, Neumayer N, Hohne-Zell B, Gratzl, M (1999) The mechanism of histamine secretion from gastric enterochromaffin-like cells. Am J Physiol Cell Physiol 277:C845–C855

    CAS  Google Scholar 

  64. Iacangelo AL, Eiden LE (1995) Chromogranin A: current status as a precursor for bioactive peptides and a granulogenic/sorting factor in the regulated secretory pathway. Regulatory Pept 58:65–88

    CAS  Google Scholar 

  65. O’Connor DT, Wu H, Gill BM, Rozansky DJ, Tang K, Mahata SK, Mahata M, Eskeland NL, Videen JS, Zhang X et al (1994) Hormone storage vesicle proteins. Transcriptional basis of the widespread neuroendocrine expression of chromogranin A, and evidence of its diverse biological actions, intracellular and extracellular. Ann NY Acad Sci 733:36–45

    PubMed  CAS  Google Scholar 

  66. Dimaline R, Evans D, Forster ER, Sandvik AK, Dockray GJ (1993) Control of gastric corpus chromogranin A messenger RNA abundance in the rat. Am J Physiol Gastrointest Liver Physiol 264:G583–G588

    CAS  Google Scholar 

  67. Dimaline R, Sandvik AK, Evans D, Forster ER, Dockray GJ (1993) Food stimulation of histidine decarboxylase messenger RNA abundance in rat gastric fundus. J Physiol (Lond) 465:449–458

    CAS  Google Scholar 

  68. Lambrecht NW, Yakubov I, Sachs G (2007) Fasting induced changes in ECL cell gene expression. Physiol Genomics 0:00252.2006v1

    Google Scholar 

  69. Kazumori H, Ishihara S, Rumi MAK, Ortega-Cava CF, Kadowaki Y, Kinoshita Y (2004) Transforming growth factor-{alpha} directly augments histidine decarboxylase and vesicular monoamine transporter 2 production in rat enterochromaffin-like cells. Am J Physiol Gastrointest Liver Physiol 286:G508–G514

    PubMed  CAS  Google Scholar 

  70. Rehavi M, Goldin M, Roz N, Weizman A (1998) Regulation of rat brain vesicular monoamine transporter by chronic treatment with ovarian hormones. Mol Brain Res 57:31–37

    PubMed  CAS  Google Scholar 

  71. Jakobsen AM, Andersson P, Saglik G, Andersson E, Kolby L, Erickson JD, Forssell-Aronsson E, Wangberg B, Ahlman H, Nilsson O (2001) Differential expression of vesicular monoamine transporter (VMAT) 1 and 2 in gastrointestinal endocrine tumours. J Pathol 195:463–472

    PubMed  CAS  Google Scholar 

  72. Atouf F, Czernichow P, Scharfmann R (1997) Expression of neuronal traits in pancreatic beta cells. Implication of neuron-restrictive silencing factor/repressor element silencing transcription factor, a neuron-restrictive silencer. J Biol Chem 272:1929–1934

    PubMed  CAS  Google Scholar 

  73. Bird JL, Wright EE, Feldman JM (1980) Pancreatic islets: a tissue rich in serotonin. Diabetes 29:304–308

    PubMed  CAS  Google Scholar 

  74. Cegrell L (1968) The occurrence of biogenic monoamines in the mammalian endocrine pancreas. Acta Physiol Scand Suppl 314:1–60

    PubMed  CAS  Google Scholar 

  75. Cetin Y (1992) Biogenic amines in the guinea pig endocrine pancreas. Life Sci 50:1343–1350

    PubMed  CAS  Google Scholar 

  76. Ekholm R, Ericson LE, Lundquist I (1971) Monoamines in the pancreatic islets of the mouse. Subcellular localization of 5-hydroxytryptamine by electron microscopic autoradiography. Diabetologia 7:339–348

    PubMed  CAS  Google Scholar 

  77. Hansen SE, Hedeskov CJ(1977) Simultaneous determination of the content of serotonin, dopamine, noradrenaline and adrenaline in pancreatic islets isolated from fed and starved mice. Acta Endocrinol (Copenh) 86:820–832

    CAS  Google Scholar 

  78. Jaim-Etcheverry G, Zieher LM (1968) Electron microscopic cytochemistry of 5-hydroxytryptamine (5-HT) in the beta cells of guinea pig endocrine pancreas. Endocrinology 83:917–923

    PubMed  CAS  Google Scholar 

  79. Lundquist I, Ahren B, Hansson C, Hakanson R (1989) Monoamines in pancreatic islets of guinea pig, hamster, rat, and mouse determined by high performance liquid chromatography. Pancreas 4:662–667

    PubMed  CAS  Google Scholar 

  80. Mahony C, Feldman JM (1977) Species variation in pancreatic islet monoamine uptake and action. Diabetes 26:257–261

    PubMed  CAS  Google Scholar 

  81. Wilson JP, Downs RW Jr, Feldman JM, Lebovitz HE (1974) Beta cell monoamines: further evidence for their role in modulating insulin secretion. Am J Physiol 227:305–312

    PubMed  CAS  Google Scholar 

  82. Zern RT, Bird JL, Feldman JM (1980) Effect of increased pancreatic islet norepinephrine, dopamine and serotonin concentration on insulin secretion in the golden hamster. Diabetologia 18:341–346

    PubMed  CAS  Google Scholar 

  83. Henquin JC (2000) Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes 49:1751–1760

    PubMed  CAS  Google Scholar 

  84. Ahren B, Wierup N, Sundler F (2006) Neuropeptides and the regulation of islet function. Diabetes 55(Suppl 2):S98–S107

    CAS  Google Scholar 

  85. Brunicardi FC, Shavelle DM, Andersen DK (1995) Neural regulation of the endocrine pancreas. Int J Pancreatol 18:177–195

    PubMed  CAS  Google Scholar 

  86. Gilon P, Henquin JC (2001) Mechanisms and physiological significance of the cholinergic control of pancreatic beta-cell function. Endocr Rev 22:565–604

    PubMed  CAS  Google Scholar 

  87. Sharp GW (1996) Mechanisms of inhibition of insulin release. Am J Physiol 271:C1781–C1799

    PubMed  CAS  Google Scholar 

  88. Jones PM, Fyles JM, Persaud SJ, Howell SL (1987) Catecholamine inhibition of Ca2+-induced insulin secretion from electrically permeabilised islets of Langerhans. FEBS Lett 219:139–144

    PubMed  CAS  Google Scholar 

  89. Lindstrom P, Sehlin J (1983) Mechanisms underlying the effects of 5-hydroxytryptamine and 5-hydroxytryptophan in pancreatic islets. A proposed role for L-aromatic amino acid decarboxylase. Endocrinology 112:1524–1529

    PubMed  CAS  Google Scholar 

  90. Persaud SJ, Jones PM, Howell SL (1993) Activation of protein kinase C partially alleviates noradrenaline inhibition of insulin secretion. Biochem J 289(Pt 2):497–501

    PubMed  CAS  Google Scholar 

  91. Sener A, Blachier F, Rasschaert J, Malaisse WJ (1990) Stimulus-secretion coupling of arginine-induced insulin release: comparison with histidine-induced insulin release. Endocrinology 127:107–113

    Article  PubMed  CAS  Google Scholar 

  92. Yajima H, Komatsu M, Sato Y, Yamada S, Yamauchi K, Sharp GW, Aizawa T, Hashizume K (2001) Norepinephrine inhibits glucose-stimulated, Ca2+-independent insulin release independently from its action on adenylyl cyclase. Endocr J 48:647–654

    PubMed  CAS  Google Scholar 

  93. Borelli MI, Villar MJ, Orezzoli A, Gagliardino JJ (1997) Presence of DOPA decarboxylase and its localisation in adult rat pancreatic islet cells. Diabetes Metab 23:161–163

    PubMed  CAS  Google Scholar 

  94. Borelli MI, Gagliardino JJ (2001) Possible modulatory effect of endogenous islet catecholamines on insulin secretion. BMC Endocr Disord 1:1

    PubMed  Google Scholar 

  95. Borelli MI, Rubio M, Garcia ME, Flores LE, Gagliardino JJ (2003) Tyrosine hydroxylase activity in the endocrine pancreas: changes induced by short-term dietary manipulation. BMC Endocr Disord 3:2

    PubMed  Google Scholar 

  96. Iturriza FC, Thibault J (1993) Immunohistochemical investigation of tyrosine-hydroxylase in the islets of Langerhans of adult mice, rats and guinea pigs. Neuroendocrinology 57:476–480

    PubMed  CAS  Google Scholar 

  97. Kitamura N, Mori Y, Hondo E, Baltazar ET, Yamada J (1999) An immunohistochemical survey of catecholamine-synthesizing enzyme-immunoreactive nerves and endocrine cells in the bovine pancreas. Anat Histol Embryol 28:81–84

    PubMed  CAS  Google Scholar 

  98. Watanabe T, Nagatsu I (1991) Immunohistochemical colocalization of insulin, aromatic L-amino acid decarboxylase and dopamine beta-hydroxylase in islet B cells of chicken pancreas. Cell Tissue Res 263:131–136

    PubMed  CAS  Google Scholar 

  99. Feldman JM, Chapman B (1975) Characterization of pancreatic islet monoamine oxidase. Metabolism 24:581–588

    PubMed  CAS  Google Scholar 

  100. Lenzen S, Freisinger-Treichel M, Panten U (1987) Monoamine oxidase in rat and bovine endocrine tissues. J Neurochem 49:1183–1190

    PubMed  CAS  Google Scholar 

  101. Lenzen S, Nahrstedt H, Panten U (1983) Monoamine oxidase in pancreatic islets, exocrine pancreas, and liver from rats. Characterization with clorgyline, deprenyl, pargyline, tranylcypromine, and amezinium. Naunyn Schmiedebergs Arch Pharmacol 324:190–195

    PubMed  CAS  Google Scholar 

  102. Pizzinat N, Chan SL, Remaury A, Morgan NG, Parini A (1999) Characterization of monoamine oxidase isoforms in human islets of Langerhans. Life Sci 65:441–448

    PubMed  CAS  Google Scholar 

  103. Saura J, Kettler R, Da Prada M, Richards JG (1992) Quantitative enzyme radioautography with 3H-Ro 41-1049 and 3H-Ro 19-6327 in vitro: localization and abundance of MAO-A and MAO-B in rat CNS, peripheral organs, and human brain. J Neurosci 12:1977–1999

    PubMed  CAS  Google Scholar 

  104. Stenstrom A, Panagiotidis G, Lundquist I (1989) Monoamine oxidase (MAO) in pancreatic islets of the mouse: some characteristics and the effect of chemical sympathectomy. Diabetes Res 11:81–84

    PubMed  CAS  Google Scholar 

  105. Huang YH, Ito A, Arai R (2005) Immunohistochemical localization of monoamine oxidase type B in pancreatic islets of the rat. J Histochem Cytochem 53:1149–1158

    PubMed  CAS  Google Scholar 

  106. Aleyassine H, Gardiner RJ (1975) Dual action of antidepressant drugs (MAO inhibitors) on insulin release. Endocrinology 96:702–710

    Article  PubMed  CAS  Google Scholar 

  107. Ahren B (2000) Autonomic regulation of islet hormone secretion-implications for health and disease. Diabetologia 43:393–410

    PubMed  CAS  Google Scholar 

  108. Rubi B, Ljubicic S, Pournourmohammadi S, Carobbio S, Armanet M, Bartley C, Maechler P (2005) Dopamine D2-like receptors are expressed in pancreatic beta cells and mediate inhibition of insulin secretion. J Biol Chem 280:36824–36832

    PubMed  CAS  Google Scholar 

  109. Shankar E, Santhosh KT, Paulose CS (2006) Dopaminergic regulation of glucose-induced insulin secretion through dopamine D2 receptors in the pancreatic islets in vitro. IUBMB Life 58:157–163

    Article  PubMed  CAS  Google Scholar 

  110. Ahren B, Taborsky GJ Jr, Porte D Jr (1986) Neuropeptidergic versus cholinergic and adrenergic regulation of islet hormone secretion. Diabetologia 29:827–836

    PubMed  CAS  Google Scholar 

  111. El-Mansoury AM, Morgan NG (1998) Activation of protein kinase C modulates alpha2-adrenergic signalling in rat pancreatic islets. Cell Signal 10:637–643

    PubMed  CAS  Google Scholar 

  112. Lundquist I (1971) Insulin secretion. Its regulation by monoamines and acid amyloglucosidase. Acta Physiol Scand Suppl 372:1–47

    PubMed  CAS  Google Scholar 

  113. Ericson LE, Hakanson R, Lundquist I (1977) Accumulation of dopamine in mouse pancreatic B-cells following injection of l-DOPA. Localization to secretory granules and inhibition of insulin secretion. Diabetologia 13:117–1124

    PubMed  CAS  Google Scholar 

  114. Arneric SP, Chow SA, Long JP, Fischer LJ (1984) Inhibition of insulin release from rat pancreatic islets by drugs that are analogues of dopamine. Diabetes 33:888–893

    PubMed  CAS  Google Scholar 

  115. Barker CJ, Leibiger IB, Leibiger B, Berggren P-O (2002) Phosphorylated inositol compounds in beta -cell stimulus–response coupling. Am J Physiol Endocrinol Metab 283:E1113–E1122

    PubMed  CAS  Google Scholar 

  116. Duttaroy A, Zimliki CL, Gautam D, Cui Y, Mears D, Wess J (2004) Muscarinic stimulation of pancreatic insulin and glucagon release is abolished in M3 muscarinic acetylcholine receptor-deficient mice. Diabetes 53:1714–1720

    PubMed  CAS  Google Scholar 

  117. Johnson DE, Yamazaki H, Ward KM, Schmidt AW, Lebel WS, Treadway JL, Gibbs EM, Zawalich WS, Rollema H (2005) Inhibitory effects of antipsychotics on carbachol-enhanced insulin secretion from perifused rat islets: role of muscarinic antagonism in antipsychotic-induced diabetes and hyperglycemia. Diabetes 54:1552–1558

    PubMed  CAS  Google Scholar 

  118. Llorente MD, Urrutia V (2006) Diabetes, psychiatric disorders, and the metabolic effects of antipsychotic medications. Clin Diabetes 24:18–24

    Google Scholar 

  119. Sernyak MJ, Leslie DL, Alarcon RD, Losonczy MF, Rosenheck R (2002) Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry 159:561–566

    PubMed  Google Scholar 

  120. Hayashi M, Otsuka M, Morimoto R, Muroyama A, Uehara S, Yamamoto A, Moriyama Y (2003) Vesicular inhibitory amino acid transporter is present in glucagon-containing secretory granules in alphaTC6 cells, mouse clonal alpha-cells, and alpha-cells of islets of Langerhans. Diabetes 52:2066–2074

    PubMed  CAS  Google Scholar 

  121. Hoy M, Maechler P, Efanov AM, Wollheim CB, Berggren PO, Gromada J (2002) Increase in cellular glutamate levels stimulates exocytosis in pancreatic beta-cells. FEBS Lett 531:199–203

    PubMed  CAS  Google Scholar 

  122. Yamada H, Otsuka M, Hayashi M, Nakatsuka S, Hamaguchi K, Yamamoto A, Moriyama Y (2001) Ca2+-dependent exocytosis of L-glutamate by alphaTC6, clonal mouse pancreatic alpha-cells. Diabetes 50:1012–1020

    PubMed  CAS  Google Scholar 

  123. Brice NL,Varadi A, Ashcroft SJ, Molnar E (2002) Metabotropic glutamate and GABA(B) receptors contribute to the modulation of glucose-stimulated insulin secretion in pancreatic beta cells. Diabetologia 45:242–252

    PubMed  CAS  Google Scholar 

  124. Storto M, Capobianco L, Battaglia G, Molinaro G, Gradini R, Riozzi B, Di Mambro A, Mitchell KJ, Bruno V, Vairetti MP, Rutter GA, Nicoletti F (2006) Insulin secretion is controlled by mGlu5 metabotropic glutamate receptors. Mol Pharmacol 69:1234–1241

    PubMed  CAS  Google Scholar 

  125. Uehara S, Muroyama A, Echigo N, Morimoto R, Otsuka M, Yatsushiro S, Moriyama Y (2004) Metabotropic glutamate receptor type 4 is involved in autoinhibitory cascade for glucagon secretion by alpha-cells of islet of Langerhans. Diabetes 53:998–1006

    PubMed  CAS  Google Scholar 

  126. Chapman AG, Nanan K, Williams M, Meldrum BS (2000) Anticonvulsant activity of two metabotropic glutamate group I antagonists selective for the mGlu5 receptor: 2-methyl-6-(phenylethynyl)-pyridine (MPEP), and (E)-6-methyl-2-styryl-pyridine (SIB 1893). Neuropharmacology 39:1567–1574

    PubMed  CAS  Google Scholar 

  127. Alexander GM, Godwin DW (2006) Metabotropic glutamate receptors as a strategic target for the treatment of epilepsy. Epilepsy Res 71:1–22

    PubMed  CAS  Google Scholar 

  128. Bai L, Zhang X, Ghishan FK (2003) Characterization of vesicular glutamate transporter in pancreatic alpha- and beta-cells and its regulation by glucose. Am J Physiol Gastrointest Liver Physiol 284:G808–G814

    PubMed  CAS  Google Scholar 

  129. Maffei A, Harris PE (2007) Targeting vesicular monoamine transporter Type 2 for noninvasive PET-based β-cell mass measurements. Expert Rev Endocrinol Metab 2:35–46

    CAS  Google Scholar 

  130. Szkudelski T (2001) The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res 50:537–546

    PubMed  CAS  Google Scholar 

  131. Polychronakos C (2004) Animal models of spontaneous autoimmune diabetes: notes on their relevance to the human disease. Curr Diab Rep 4:151–154

    PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the Public Health Service, National Institute of Health, National Institute of Diabetes and Digestive and Kidney Diseases 2 RO1 DK63567-03 and 1R01-DK077493-01, Telethon-Juvenile Diabetes Research Foundation International GJT04003.

Funding

The authors have no financial or other arrangements that represent a conflict of interest.

Author information

Authors and Affiliations

  1. Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, CNR, Naples, 80131, Italy

    Paul E. Harris, Caterina Ferrara, Pasquale Barba & Antonella Maffei

  2. Department of Medicine, Columbia University Medical Center, Black Building 20th floor, 650W 168th Street, New York, NY, 10032, USA

    Paul E. Harris, Teresa Polito, Matthew Freeby & Antonella Maffei

Authors
  1. Paul E. Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Caterina Ferrara
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pasquale Barba
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Teresa Polito
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matthew Freeby
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antonella Maffei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul E. Harris.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Harris, P.E., Ferrara, C., Barba, P. et al. VMAT2 gene expression and function as it applies to imaging β-cell mass. J Mol Med 86, 5–16 (2008). https://doi.org/10.1007/s00109-007-0242-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-007-0242-x

Keywords

Search

Navigation