helospectin-i and Diabetes-Mellitus--Type-1

A reliable method for in vivo quantification of pancreatic beta cell mass (BCM) could lead to further insight into the pathophysiology of diabetes. The glucagon-like peptide 1 receptor, abundantly expressed on beta cells, may be a suitable target for imaging. We investigated the potential of radiotracer imaging with the GLP-1 analogue exendin labelled with indium-111 for determination of BCM in vivo in a rodent model of beta cell loss and in patients with type 1 diabetes and healthy individuals.. The targeting of (111)In-labelled exendin was examined in a rat model of alloxan-induced beta cell loss. Rats were injected with 15 MBq (111)In-labelled exendin and single photon emission computed tomography (SPECT) acquisition was performed 1 h post injection, followed by dissection, biodistribution and ex vivo autoradiography studies of pancreatic sections. BCM was determined by morphometric analysis after staining with an anti-insulin antibody. For clinical evaluation SPECT was acquired 4, 24 and 48 h after injection of 150 MBq (111)In-labelled exendin in five patients with type 1 diabetes and five healthy individuals. The tracer uptake was determined by quantitative analysis of the SPECT images.. In rats, (111)In-labelled exendin specifically targets the beta cells and pancreatic uptake is highly correlated with BCM. In humans, the pancreas was visible in SPECT images and the pancreatic uptake showed high interindividual variation with a substantially lower uptake in patients with type 1 diabetes.. These studies indicate that (111)In-labelled exendin may be suitable for non-invasive quantification of BCM.. ClinicalTrials.gov NCT01825148, EudraCT: 2012-000619-10.

Topics: Adolescent; Adult; Animals; Diabetes Mellitus, Type 1; Female; Glucagon-Like Peptide-1 Receptor; Humans; Indium Radioisotopes; Insulin-Secreting Cells; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Peptides; Radiopharmaceuticals; Rats; Receptors, Glucagon; Time Factors; Tomography, Emission-Computed, Single-Photon; Young Adult

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.

Topics: Animals; Diabetes Mellitus, Type 1; Female; Humans; Indium Radioisotopes; Insulin-Secreting Cells; Intercellular Signaling Peptides and Proteins; Male; Peptides; Tomography, Emission-Computed, Single-Photon