Noninvasive Monitoring of Glycemia-Induced Regulation of GLP-1R Expression in Murine and Human Islets of Langerhans

Mijke Buitinga*, Christian M. Cohrs, Wael A. Eter, Lieke Claessens-Joosten, Cathelijne Frielink, Desiree Bos, Gerwin Sandker, Maarten Brom, Stephan Speier, Martin Gotthardt

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)

Abstract

Glucagon-like peptide 1 receptor (GLP-1R) imaging with radiolabeled 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 (BG) 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 BG 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 noninvasively. Our findings have significant implications for clinical practice, indicating that BG levels should be near-normalized for at least 3 weeks prior to GLP-1R agonist treatment or quantitative radiolabeled exendin imaging for BCM analysis.

Original languageEnglish
Pages (from-to)2246-2252
Number of pages7
JournalDiabetes
Volume69
Issue number11
DOIs
Publication statusPublished - Nov 2020

Keywords

  • BETA-CELL MASS
  • GLUCAGON-LIKE PEPTIDE-1
  • BLOOD-GLUCOSE IMPROVES
  • HYPERGLYCEMIA
  • RECEPTOR
  • ONSET
  • NORMALIZATION
  • PANCREAS

Cite this