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Journal of Histochemistry and Cytochemistry, Vol. 51, 1027-1040, August 2003, Copyright © 2003, The Histochemical Society, Inc.

ARTICLE

Expression of the Two Isoforms of the Vesicular Monoamine Transporter (VMAT1 and VMAT2) in the Endocrine Pancreas and Pancreatic Endocrine Tumors

Martin Anlaufa,d, Rolf Eisseleb, Martin K.-H. Schäfera, Lee E. Eidenc, Rudolf Arnoldb, Ursula Pauserd, Günter Klöppeld, and Eberhard Weihea
a Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University of Marburg
b Department of Gastroenterology and Endocrinology, Philipps University of Marburg, Marburg, Germany
c Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, NIMH, Bethesda, Maryland
d Department of Pathology, University of Kiel, Kiel, Germany

Correspondence to: Eberhard Weihe, Dept. of Molecular Neuroscience, Inst. of Anatomy and Cell Biology, Philipps University, Robert-Koch Str. 6, 35037 Marburg, Germany. E-mail: weihe@staff.uni-marburg.de

The uptake of monoamines into the secretory granules of monoamine-storing neuroendocrine cells is mediated by vesicular monoamine transporter protein 1 or 2 (VMAT1 or VMAT2). This study analyzed the expression of VMAT1 and VMAT2 in endocrine cells of normal human and monkey pancreas. The expression of VMAT1 and VMAT2 was also examined in infants with hyperinsulinemic hypoglycemia and in adults with pancreatic endocrine tumors (PETs). Using immunohistochemistry (IHC) and in situ hybridization (ISH), we demonstrated the mutually exclusive expression of VMAT1 in endocrine cells of the duct system and of VMAT2 in many cells of the islets of Langerhans. By confocal laser scanning microscopy, VMAT1-positive cells were identified as enterochromaffin (EC) cells and VMAT2-positive cells as ß-cells. In PETs, VMAT1 was found exclusively in all serotonin-containing tumors. In contrast, VMAT2 expression was lost in many insulinomas, independent of their biological behavior. VMAT2 was expressed by some non-insulin-producing tumors. The mutually exclusive expression of VMAT1 in EC cells and of VMAT2 in ß-cells suggests that both cell types store monoamines. Monoamine storage mediated by VMAT1 in EC cells is apparently maintained in EC cell tumors. In contrast, many insulinomas appear to lose their ability to accumulate monoamines via VMAT2. (J Histochem Cytochem 51:1027–1040, 2003)

Key Words: vesicular monoamine, transporter, EC cell, pancreatic islet, insulin, glucagon, somatostatin, pancreatic polypeptide, neuroendocrine tumor


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