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Updated: Jan 8, 2026
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Assessing Replication and Beta Cell Function in Adenovirally-transduced Isolated Rodent Islets
Published on: June 25, 2012
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Ppid is necessary for overnutrition-induced β-cell loss.
Brittney A Covington1, Zihan Tang1, Lisette A Maddison1
1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States.
American Journal of Physiology. Endocrinology and Metabolism
|December 15, 2025
Summary
Cyclophilin D (Ppid) drives beta-cell death in type 2 diabetes models. Inhibiting Ppid protects beta-cell mass, revealing a key target for T2D treatment.
Area of Science:
- Endocrinology
- Mitochondrial Biology
- Diabetes Research
Background:
- Type 2 diabetes (T2D) is characterized by progressive loss of functional beta-cell mass.
- Overnutrition in zebrafish insulin-resistant models (zMIR) induces islet inflammation and nocturnal beta-cell death.
Purpose of the Study:
- To investigate the role of cyclophilin D (Ppid) in mediating beta-cell loss during overnutrition-induced insulin resistance.
- To identify therapeutic targets for preserving beta-cell mass in T2D.
Main Methods:
- Utilized a zebrafish insulin-resistant model (zMIR) with genetic manipulation of Ppid.
- Administered Ppid inhibitor cyclosporin A (CsA), mitochondrial ROS scavenger mito-TEMPO, and mitochondrial calcium chelator Ru360.
- Assessed beta-cell mass, islet inflammation, and macrophage recruitment.
Main Results:
- Cyclosporin A (CsA) prevented nocturnal beta-cell death in zMIR.
- Mitochondrial-targeted interventions (mito-TEMPO, Ru360) protected beta cells, implicating the mitochondrial permeability transition pore (mPTP).
- Global Ppid knockout preserved beta-cell mass, while beta-cell-specific Ppid re-expression restored and exacerbated beta-cell loss, which was CsA-sensitive.
Conclusions:
- Ppid acts as a beta-cell-intrinsic mediator of overnutrition-induced beta-cell loss.
- Targeting Ppid offers a potential therapeutic strategy for preserving beta-cell function in type 2 diabetes.
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