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Leprdb Mouse Model of Type 2 Diabetes: Pancreatic Islet Isolation and Live-cell 2-Photon Imaging Of Intact Islets
Published on: May 11, 2015
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Beta cell specific probing with fluorescent exendin-4 is progressively reduced in type 2 diabetic mouse models
Janne Lehtonen1, Lauge Schäffer2, Morten Grønbech Rasch3
1a Department of Histology & Imaging , Novo Nordisk A/S , Måløv , Denmark.
Islets
|March 11, 2016
Summary
Fluorescent exendin-4 probes specifically label mouse pancreatic beta cells. In type 2 diabetes models, probe intensity decreases, suggesting GLP-1R probes may track beta cell function, not just mass.
Area of Science:
- Biomedical imaging
- Endocrinology
- Molecular imaging
Background:
- Glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 probes show potential for in vivo beta cell imaging.
- Uncertainty exists regarding exendin-4 probe specificity and GLP-1R expression in type 2 diabetes.
Purpose of the Study:
- To confirm the beta cell specificity of exendin-4 probes in mice.
- To investigate the impact of type 2 diabetes on GLP-1R expression and probe binding.
Main Methods:
- In vivo and ex vivo imaging of fluorescent exendin-4 probes in mice.
- Co-localization studies to assess cell-type specificity.
- Analysis of GLP-1R expression in type 2 diabetes models (db/db and Diet-Induced Obese).
Main Results:
- Fluorescent exendin-4 probes demonstrated distinct, GLP-1R-dependent labeling of pancreatic islets in mice.
- Probes exhibited nearly 100% beta cell specificity, with minimal binding to other cell types.
- Type 2 diabetes models showed reduced probe intensity and decreased GLP-1R protein levels, particularly in db/db mice.
Conclusions:
- Exendin-4 based probes are highly specific for beta cells in mice.
- GLP-1R targeting probes may serve as a tool to monitor beta cell function in type 2 diabetes, rather than solely beta cell mass.
