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Aims/hypothesis: 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., Methods: 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., Results: 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., Conclusions/interpretation: These studies indicate that (111)In-labelled exendin may be suitable for non-invasive quantification of BCM., Trial Registration: ClinicalTrials.gov NCT01825148, EudraCT: 2012-000619-10.

High-resolution large-scale two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) combined with computer-assisted image analysis was used to construct a database of secretagogue/second messenger-induced phosphoprotein modifications in intact rat pancreatic acinar cells. Isolated acini were labeled with 32Pi, exposed to hormones and other test agents, and subjected to large-scale 2D-PAGE and autoradiography. This procedure resolved 500 phosphoproteins in pancreatic acinar whole cell lysates, approximately 90% of which were localized in the soluble fraction of centrifuged samples. Soluble proteins were further characterized as to heat and acid stability. Cholecystokinin (CCK), carbachol, and bombesin altered the phosphorylation state of about 27 proteins with both increases and decreases observed. Subsets of proteins were phosphorylated in response to phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), calcium ionophore A-23187, and adenosine 3',5'-cyclic monophosphate (cAMP) analogue 8-bromo-cAMP. One of these proteins was identified as the myristoylated, alanine-rich, C-kinase substrate (MARCKS) protein by immunoprecipitation. The time course and dose response of phosphorylation changes due to CCK showed considerable variation between proteins, although a temporal hierarchy of phosphorylation events was clearly exhibited. Particularly striking was the rapid dephosphorylation within 30 s of a 19-kDa soluble protein to a minimum of 20 +/- 1% of control. Increased phosphorylation of the MARCKS and other TPA-regulated proteins suggests that CCK, carbachol, bombesin, and the CCK partial agonist, JMV-180, all activate protein kinase C in intact acini.