Human-Islet-Checklist.pdf (81.79 kB)
Download fileNon-invasive monitoring of glycemia-induced regulation of GLP-1R expression in murine and human islets of langerhans
figure
posted on 2020-08-25, 18:44 authored by Ada AdminAda Admin, Mijke Buitinga, Christian M.Cohrs, Wael A.Eter, Lieke Claessens-Joosten, Cathelijne Frielink, Desirée Bos, Gerwin Sandker, Maarten Brom, Stephan Speier, Martin GotthardtGLP-1R
imaging with radiolabelled exendin has proven to be a powerful tool to quantify
beta-cell mass (BCM) in vivo. As
GLP-1R expression is thought to be influenced by glycemic control, we examined the effect of blood glucose levels on GLP-1R-mediated exendin
uptake in both murine and human islets and its implications for BCM
quantification. Periods of hyperglycemia
significantly reduced exendin uptake in murine and human islets, which was
paralleled by a reduction in GLP-1R expression. Detailed mapping of the tracer
uptake and insulin and GLP-1R expression conclusively demonstrated that the
observed reduction in tracer uptake directly correlates to GLP-1R expression
levels. Importantly, the linear correlation between tracer uptake and beta-cell
area was maintained in spite of the reduced GLP-1R expression levels.
Subsequent normalization of blood glucose levels restored absolute tracer
uptake and GLP-1R expression in beta-cells and the observed loss in islet
volume was halted.
This manuscript emphasizes the potency of nuclear imaging techniques to monitor receptor regulation non-invasively. Our findings have significant implications for clinical practice, indicating that blood glucose levels should be near-normalized for at least three weeks prior to GLP-1R agonist treatment or quantitative radiolabeled exendin imaging for BCM analysis.