Hellström-Lindahl E, Danielsson A, Ponten F, Czernichow P, Korsgren O, Johansson L, Eriksson O
Acta Diabetol 53 (3) 413-421 [2016-06-00; online 2015-10-14]
To address questions regarding onset and progression of types 1 and 2 diabetes (T1D/T2D), surrogate imaging biomarkers for beta cell function and mass are needed. Here, we assess the potential of GPR44 as a surrogate marker for beta cells, in a direct comparison with clinically used biomarker VMAT2. GPR44 surface availability was assessed by flow cytometry of human beta cells. RNA transcription levels in different pancreas compartments were evaluated. The density of GPR44 receptor in endocrine and exocrine tissues was assessed by the radiolabeled GPR44 ligand [(3)H]AZD 3825. A direct comparison with the established beta cell marker VMAT2 was performed by radiolabeled [(3)H]DTBZ. GPR44 was available on the cell surface, and pancreatic RNA levels were restricted to the islets of Langerhans. [(3)H]AZD 3825 had nanomolar affinity for GPR44 in human islets and EndoC-βH1 beta cells, and the specific binding to human beta cells was close to 50 times higher than in exocrine preparations. The endocrine-to-exocrine binding ratio was approximately 10 times higher for [(3)H]AZD 3825 than for [(3)H]DTBZ. GPR44 is a highly beta cell-specific target, which potentially offers improved imaging contrast between the human beta cell and the exocrine pancreas.
Bioinformatics Compute and Storage [Service]
NGI Stockholm (Genomics Applications) [Service]
NGI Stockholm (Genomics Production) [Service]
National Genomics Infrastructure [Service]
Tissue Profiling [Collaborative]