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Non-invasive monitoring of glycemia-induced regulation of GLP-1R expression in murine and human islets of langerhans

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posted on 25.08.2020 by Ada Admin, Mijke Buitinga, Christian M.Cohrs, Wael A.Eter, Lieke Claessens-Joosten, Cathelijne Frielink, Desirée Bos, Gerwin Sandker, Maarten Brom, Stephan Speier, Martin Gotthardt
GLP-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.

Funding

Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115797 (INNODIA) and No 945268 (INNODIA HARVEST). European Commission Seventh Framework Programme FP7 Coordination of Non-Community Research Programmes BetaCure/602812

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