Diabetes results from a reduction in the number of islet beta cells in the pancreas, which leads to insufficient insulin secretion and high blood glucose levels (hyperglycemia). Currently, insulin secretion is used as a surrogate measure of beta cell mass. However serum insulin concentrations provide an imprecise measure of beta cell mass, and no reliable non-invasive measure of beta cell mass has been available, until now. In a study appearing online on May 18 in advance of print publication in the June issue of the Journal of Clinical Investigation, Paul Harris and colleagues from Columbia University in New York report that positron emission tomography (PET)-based quantitation of pancreatic radiolabeled VMAT2 receptors in diabetic rats is a reliable and non-invasive way to measure beta cell mass.

The authors exploited the finding that type 2 vesicular monoamine transporters (VMAT2) are expressed in human islet beta cells within the pancreas, as well as in tissues of the central nervous system. As the radioligand [11C]Dihydrotetrabenazine (DTBZ) binds specifically to VMAT2 and is currently used in clinical imaging of the brain, the authors were able to use DTBZ to estimate beta cell mass in rats with type 1 diabetes. In longitudinal PET studies, the authors saw a significant decline in pancreatic uptake of DTBZ that preceded the loss of glycemic control in the diabetic rat. These studies suggest that PET-based quantitation of VMAT2 receptors could provide a non-invasive measurement of beta cell mass that could be used to study the pathogenesis of diabetes and to monitor therapeutic interventions.

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Contact: Brooke Grindlinger
press_releases@the-jci.org
212-342-9006
Journal of Clinical Investigation
18-May-2006

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