Insights For Optimizing Vmat2 -Based Human Beta Cell Imaging In Animal Models

Understanding the number of beta cells (or their volume) a person has is critical to understanding the T1D disease process because individuals lose beta cells over the course of the disease. However, imaging of beta cell mass (their total volume) is a major challenge in diabetes research because of their obscured and dispersed location in the pancreas.  One protein called VMAT2 is abundantly produced in human beta cells and has been the focus of research to develop a beta cell imaging agent. By attaching a radioactive label to VMAT2 and then measuring the amount of radioactivity emitted, the protein has  been employed for pancreatic islet imaging in humans. Unfortunately, there have been conflicting reports and controversy on VMAT2-based imaging in rodent pancreas raising questions about its overall utility.  In this report, the researchers compared VMAT2 gene expression patterns in the mouse, rat, pig and human pancreas, to identify appropriate animal models to further validate and optimize its imaging use in humans. They found that the VMAT2 protein was not expressed in beta cells in the adult pancreas of common mouse or rat laboratory strains, in contrast to its expression in beta cells in the pancreas of pigs and humans.  This work shows that primates and pigs are suitable models for VMAT2-based imaging of beta cells, but not rodents.  This should clarify the plans for addition study of this potential beta cell imaging technique.

Ramifications for Individuals with T1D:

This research clarifies the potential value of VMAT2-based beta cell mass or volume imaging in humans.  There is much interest now in an ongoing academic-industry proof of concept trial of this imaging technique in patients with T1D.

Investigators and Institutions:

Schäfer MK, Hartwig NR, Kalmbach N, Klietz M, Anlauf M, Eiden LE, Weihe E. with the Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University Marburg, Robert-Koch-Straße 8, 35037 Marburg, Germany.

JDRF Involvement:

JDRF funded many of the preclinical studies developing VMAT2 as a target for non-invasive imaging, as well as early proof of concept studies in T1D vs. healthy controls. 

Reference:

Schäfer MK, Hartwig NR, and others. Species-specific vesicular monoamine transporter 2 (VMAT2) expression in mammalian pancreatic beta cells: implications for optimising radioligand-based human beta cell mass (BCM) imaging in animal models. Diabetologia. 2013 May;56(5):1047-56. doi: 10.1007/s00125-013-2847-7. Epub 2013 Feb 13.