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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
PANIC-ATTAC: a mouse model for inducible and reversible beta-cell ablation.
Zhao V Wang1, James Mu, Todd D Schraw
1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA.
Diabetes
|May 13, 2008
Summary
A new mouse model, PANIC-ATTAC, allows for inducible and reversible pancreatic beta-cell ablation. This model shows significant beta-cell recovery and may help identify beta-cell precursors for diabetes research.
Area of Science:
- Endocrinology
- Diabetes Research
- Stem Cell Biology
Background:
- Islet transplantation is limited in clinical application.
- Identifying pancreatic beta-cell stem cells for beta-cell mass reconstitution remains a challenge.
Purpose of the Study:
- To present a novel mouse model for inducible and reversible pancreatic beta-cell ablation.
- To investigate beta-cell regeneration and potential precursor identification.
Main Methods:
- Developed the PANIC-ATTAC (pancreatic islet beta-cell apoptosis through targeted activation of caspase 8) mouse model.
- Induced beta-cell death via apoptosis using a chemical dimerizer.
- Observed reversibility of diabetes phenotype and beta-cell loss.
Main Results:
- Demonstrated full reversibility of diabetes and beta-cell loss within 2 months.
- Showed enhanced beta-cell recovery with pharmacological interventions (GLP-1 axis, PPAR-gamma agonists).
- Identified a population of GLUT2(+)/insulin(-) cells as potential beta-cell precursors.
Conclusions:
- The PANIC-ATTAC mouse is a valuable model for inducible and reversible beta-cell ablation.
- Applications include beta-cell precursor identification, glucotoxicity studies, and evaluating diabetes pharmacotherapies.
