Expression of the two isoforms of the vesicular monoamine transporter (VMAT1 and VMAT2) in the endocrine pancreas and pancreatic endocrine tumors.
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 beta-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 beta-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.
Anlauf
Martin
M
Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University of Marburg, Marburg, Germany.
Eissele
Rolf
R
Schäfer
Martin K-H
MK
Eiden
Lee E
LE
Arnold
Rudolf
R
Pauser
Ursula
U
Klöppel
Günter
G
Weihe
Eberhard
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D004759:Enterochromaffin Cells / Q000378:metabolism / Q000473:pathology; D015408:Gastrinoma / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D007340:Insulinoma / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D018613:Microscopy, Confocal; D008875:Middle Aged; D009479:Neuropeptides; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D020033:Protein Isoforms; C493449:SLC18A1 protein, human; C493452:SLC18A2 protein, human; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins