Calcineurin/NFAT signaling in the β‐cell: From diabetes to new therapeutics
@article{Heit2007CalcineurinNFATSI, title={Calcineurin/NFAT signaling in the $\beta$‐cell: From diabetes to new therapeutics}, author={Jeremy J. Heit}, journal={BioEssays}, year={2007}, volume={29} }
Pancreatic β‐cells in the islet of Langerhans produce the hormone insulin, which maintains blood glucose homeostasis. Perturbations in β‐cell function may lead to impairment of insulin production and secretion and the onset of diabetes mellitus. Several essential β‐cell factors have been identified that are required for normal β‐cell function, including six genes that when mutated give rise to inherited forms of diabetes known as Maturity Onset Diabetes of the Young (MODY). However, the…
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References
SHOWING 1-10 OF 96 REFERENCES
Calcineurin/NFAT signalling regulates pancreatic β-cell growth and function
- Biology, MedicineNature
- 2006
Calcineurin/NFAT signalling regulates multiple factors that control growth and hallmark β-cell functions, revealing unique models for the pathogenesis and therapy of diabetes.
Insulin - producing cells derived from stem cells: recent progress and future directions
- Biology, MedicineJournal of cellular and molecular medicine
- 2006
The different approaches that have been used to obtain insulin‐producing cells from embryonic and adult stem cells are summarized, and the main problems that hamper the clinical applications of this technology are summarized.
Molecular Control of Cell Cycle Progression in the Pancreatic β-Cell
- Biology
- 2006
In this review, the molecular details of cell cycle control as they relate to the pancreatic beta-cell are reviewed and can serve as a common basis and also a roadmap for those interested in developing novel strategies for enhancing beta- cell replication and improving insulin production in animal models as well as in human pancreatic Beta-cells.
INHIBITION OF GLUCOSE‐STIMULATED INSULIN RELEASE FROM βTC3 CELLS AND RODENT ISLETS BY AN ANALOG OF FK506
- Biology, MedicineTransplantation
- 1993
The effects of an analog of a newer agent termed L-683, 590 on insulin secretion by an islet tumor line, βTC3, and rat islets are studied, and the effects of this drug to those of cyclosporine are compared, since both cause similar immunosuppression.
Inhibition of human insulin gene transcription by the immunosuppressive drugs cyclosporin A and tacrolimus in primary, mature islets of transgenic mice.
- Biology, MedicineMolecular pharmacology
- 2003
The high potency of cyclosporin A and tacrolimus in normal islets suggests that inhibition of insulin gene transcription by cyclospora A and Tacrolima is clinically important and is one mechanism of the diabetogenic effect of these immunosuppressive drugs.
Diabetogenic effect of cyclosporin A is mediated by interference with mitochondrial function of pancreatic B-cells.
- Biology, MedicineMolecular pharmacology
- 2001
It is concluded that CsA alters B-cell function by inhibiting the mitochondrial PTP, which terminates the oscillatory activity that is indispensable for adequate insulin secretion.
TRANSCRIPTIONAL INHIBITION OF INSULIN BY FK506 AND POSSIBLE INVOLVEMENT OF FK506 BINDING PROTEIN‐12 IN PANCREATIC β-CELL
- Biology, MedicineTransplantation
- 1995
Findings point to the reduction of unidentified nuclear factors for insulin mRNA transcription caused by the binding of FK506 to FKBP-12 and a subsequent inhibition of calcineurin in the β-cells.
Identification of calcineurin as a key signalling enzyme in T-lymphocyte activation
- Biology, ChemistryNature
- 1992
It is reported here that overexpression of calcineurin in Jurkat cells renders them more resistant to the effects of CsA and FK506 and augments both NFAT- and NFIL2A-dependent transcription.
Secretory defects induced by immunosuppressive agents
on human pancreatic β-cells
- Biology, MedicineActa Diabetologica
- 2002
In vitro data are consistent with the reported in vivo diabetogenicity of CsA and FK506 and point to MMF as the ideal immunosuppressive agent from a pancreatic β-cell point of view.
Direct Effects of Cyclosporin A on Human Pancreatic β-cells
- Medicine, BiologyDiabetes
- 1986
It is concluded that CyA has a direct inhibitory effect on insulin release from human pancreatic islets with a concomitant increase in the residual insulin content.