Vesicular monoamine transporter, type 2 (vmat2) expression as it compares to insulin and pancreatic polypeptide in the head, body and tail of the human pancreas

Abstract

The vesicular monoamine transporter, type 2 (VMAT2) is responsible for sequestering monoamine neurotransmitters into exocytic vesicles in neurons, enterochromaffin-like cells of the stomach and cells arising from the common myeloid progenitor. VMAT2 is also present in the pancreas and is expressed by insulin producing β cells, but not by glucagon or somatostatin expressing islet cells. Positron emission tomography (PET) targeting of VMAT2 is currently being evaluated as a non-invasive tool to measure β cell mass (BCM) in living humans. In recent trials, PET measurements of VMAT2 in the pancreas overestimated BCM in type 1 diabetes (T1D) patients predicted to have little to no BCM by metabolic measures. Recently, tissue immunohistochemistry studies suggested that VMAT2 staining may also co-localize with pancreatic polypeptide (PP) staining cells in pancreas tissue, but these studies were not quantitative. In this report, we evaluated VMAT2 specificity for β cells in sub-regions of the human pancreas using antibodies targeting VMAT2, insulin and PP by double-label immunofluorescence. Immunostaining for VMAT2 and insulin demonstrated 89 ± 8% overlap in the body and tail of the pancreas. However, 44 ± 12% and 53 ± 15% of VMAT2 cells co-stained with PP- and insulin-staining cells, respectively in the pancreatic head. Significant co-staining for VMAT2 and PP cells in the head of the pancreas may partly explain the apparent overestimation of BCM in T1D by PET. Specific targeting of the pancreatic body and tail using VMAT2 PET scanning may reflect BCM more accurately.