Beta-Cell Dysfunction Induced by Tacrolimus: A Way to Explain Type 2 Diabetes?
Abstract
:1. Introduction
2. Physiology of Pancreatic Islets
3. Pancreatic β-Cell
3.1. Mechanisms of Insulin Secretion
3.2. Functional Regulation of β-Cell
3.2.1. Calcineurin-NFAT Pathway
3.2.2. Insulin Receptor-IRS1-PI3K-AKT Pathway
3.2.3. mTOR Pathway
3.2.4. Nuclear Factors Relevant in β-Cells Metabolism: PDX1, MafA, NeuroD and FoxO1
3.2.5. TGF-β Receptor Pathway
4. Dysfunction of β-Cell: Insulin Resistance, Glucolipotoxicity and Diabetes
4.1. Glucolipotoxicity and the Calcineurin-NFAT Pathway
4.2. Gluocolipotoxicity and the Insulin Receptor-IRS1-PI3K-AKT Pathway
4.3. Glucolipotoxicity and the mTOR Pathway
4.4. Glucolipotoxicity and the Nuclear Factors: PDX, MafA, NeuroD and FoxO1
4.5. Glucolipotoxicity and the TGF-β Receptor Pathway
5. Post-Transplant Diabetes Mellitus (PTDM) and Tacrolimus
5.1. Common Actions between Tacrolimus and Glucolipotoxicity
5.2. Calcienurin-NFAT Pathway Inhibition Contributes Diabetogenic Effect of TAC and CsA
5.3. TAC and PTDM: Beyond the Inhibition of Calcienurin-NFAT Pathway
5.4. TAC Accelerates an On-Going Process: Insulin Receptor-IRS1-PI3K-Akt Pathway
5.5. TAC Accelerates an On-Going Process: mTOR Pathway
5.6. TAC Accelerates an On-Going Process: PDX-1, MafA, NeuroD and FoxO1
5.7. TAC Accelerates and On-Going Process: TGF-β Receptor Pathway and Intracellular Calcium
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Rodriguez-Rodriguez, A.E.; Porrini, E.; Torres, A. Beta-Cell Dysfunction Induced by Tacrolimus: A Way to Explain Type 2 Diabetes? Int. J. Mol. Sci. 2021, 22, 10311. https://doi.org/10.3390/ijms221910311
Rodriguez-Rodriguez AE, Porrini E, Torres A. Beta-Cell Dysfunction Induced by Tacrolimus: A Way to Explain Type 2 Diabetes? International Journal of Molecular Sciences. 2021; 22(19):10311. https://doi.org/10.3390/ijms221910311
Chicago/Turabian StyleRodriguez-Rodriguez, Ana Elena, Esteban Porrini, and Armando Torres. 2021. "Beta-Cell Dysfunction Induced by Tacrolimus: A Way to Explain Type 2 Diabetes?" International Journal of Molecular Sciences 22, no. 19: 10311. https://doi.org/10.3390/ijms221910311