Inside the pancreas: progress and challenges of human beta cell mass quantification

Abstract

The accurate quantification of beta cell mass in humans is one of the key challenges in understanding the role of beta cell loss and dysfunction in the pathogenesis of diabetes mellitus. Autopsy studies indicate that beta cell loss is not only a hallmark of autoimmune diabetes but also plays a pivotal role in type 2 diabetes, owing to the toxic effects of lipids, glucose and cytokines. Thus, there is an urgent need for non-invasive clinical techniques for beta cell mass quantification, which should be optimally integrated into standard diagnostic equipment in hospitals. In this issue of Diabetologia (Brom et al DOI 10.1007/s00125-014-3166-3) it is reported that single photon emission computed tomography (SPECT) data with (111)indium-labelled glucagon-like peptide-1 (GLP-1) receptor agonist exendin-3 correlate with the morphometric analysis of beta cell mass in a rat model of alloxan-induced diabetes. With this validation, the authors were able to demonstrate a significant loss of beta cell mass in C-peptide-negative type 1 diabetic patients. Thus, (111)indium-labelled exendin-3 could serve as a model tracer for future studies of larger cohorts of diabetic patients to monitor the dynamics of beta cell loss and regeneration. Despite the recent progress from SPECT imaging data there remain open questions that await clarification in the near future such as variations in GLP-1 receptor density and physiological variation of beta cell mass in relation to beta cell function. The use of GLP-1-based tracer analysis may open new clinical avenues for non-invasive quantification of beta cell mass in patients with newly diagnosed type 1 diabetes and prediabetic individuals with high titres of autoantibodies.