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-peptidenegative type 1 diabetic patients. Thus, The perfect tracer for non-invasive quantification of beta cell massTracers are chemical compounds with high affinity to specific cell types either through binding to cell surface structures or intracellular accumulation. Coupling with paramagnetic particles, radioisotopes or fluorophores allows in vivo detection by MRI, single photon emission computed tomography (SPECT) or photonsensors. Irrespective of the detection method, the tracer used for labelling beta cells must have certain key features for in vivo quantification of beta cell mass, as detailed in the text box below.• A high sensitivity and affinity for specific structures of the beta cell -through binding to surface structures (e.g. GLP-1 derivatives, DTBZ or single chain antibodies) or -tracer enrichment in beta cells by metabolism (e.g. fluorodeoxyglucose, sulfonylurea derivatives) • No toxic effects • Effective labelling of a high proportion of beta cell mass • Rapid tracer washout to repeat the diagnostic process

Non-invasive Beta-cell Imaging: Visualization, Quantification, and Beyond

“…Direct information regarding BCM itself provides a novel parameter for understanding the pathophysiology of diabetes and evaluating the efficacy of new and existing antidiabetic therapy. However, the conventional histological method for evaluating BCM using pancreas samples through autopsy or surgery is invasive and is limited to cross-sectional observations (20). This method also raises certain concerns in terms of the restricted sampling area and staining evenness in view of representing the BCM of the entire pancreas (20).…”

“…However, the conventional histological method for evaluating BCM using pancreas samples through autopsy or surgery is invasive and is limited to cross-sectional observations (20). This method also raises certain concerns in terms of the restricted sampling area and staining evenness in view of representing the BCM of the entire pancreas (20). A novel technique for noninvasive BCM monitoring is therefore an urgent need in basic research and clinical fields.…”

The CREBRF diabetes-protective rs373863828-A allele is associated with enhanced early insulin release in men of Māori and Pacific ancestry

“…This may suggest that the A allele is associated with improved maximal ability for β-cells to release insulin, rather than responding to a greater glucose stimulus for release. Increased β-cell insulin secretion could be the result of improved secretory capacity or elevated β-cell mass [40]. While the effect of rs373863828 genotype on either β-cell development, mass or secretory capacity has not been investigated, β-cell replication during infancy is a major indicator of β-cell mass in adults [41].…”

An Update on the Effect of Incretin-Based Therapies on β-Cell Function and Mass

“…More accurate and non-invasive methods to assess functional β-cell mass in vivo are needed to facilitate the evaluation of any treatment on β-cell mass in humans [ 99 ]. Furthermore, additional long-term RCTs evaluating relatively larger numbers of patients, especially patients with new-onset T1DM and at different stages of preclinical T1DM, are needed to confirm the effects of GLP-1 RAs and DPP4Is on β-cell mass.…”