Impaired TFEB activation and mitophagy as a cause of PPP3/calcineurin inhibitor-induced pancreatic β-cell dysfunction

Park, Kihyoun; Sonn, Seong Keun; Seo, Seungwoon; Kim, Jinyoung; Hur, Kyu Yeon; Oh, Goo Taeg; Lee, Myung-Shik

doi:10.1080/15548627.2022.2132686

Cited by 10 publications

(2 citation statements)

References 59 publications

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“…The importance of mitophagy in β‐cell function was also shown in mice that developed β‐cell dysfunction and glucose intolerance after treatment with FK506, a calcineurin inhibitor, which impeded activation of calcineurin and TFEB (Figure 1 ). Post‐transplantation diabetes mellitus developing in up to 40% of patients after transplantation and treatment with calcineurin inhibitors, such as FK506 53 , could be partly due to diminished autophagy or mitophagy, as calcineurin inhibitors, such as FK506, inhibit calcineurin‐dependent activation of TFEB and autophagy or mitophagy 54 . In addition to mitophagy inhibition, FK506 might also impair proliferation of β‐cells 55 .…”

Section: Mitophagy and Er‐phagy In β‐Cellsmentioning

confidence: 99%

Role of β‐cell autophagy in β‐cell physiology and the development of diabetes

Yasasilka,

Lee

2024

J of Diabetes Invest

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Elucidating the molecular mechanism of autophagy was a landmark in understanding not only the physiology of cells and tissues, but also the pathogenesis of diverse diseases, including diabetes and metabolic disorders. Autophagy of pancreatic β‐cells plays a pivotal role in the maintenance of the mass, structure and function of β‐cells, whose dysregulation can lead to abnormal metabolic profiles or diabetes. Modulators of autophagy are being developed to improve metabolic profile and β‐cell function through the removal of harmful materials and rejuvenation of organelles, such as mitochondria and endoplasmic reticulum. Among the known antidiabetic drugs, glucagon‐like peptide‐1 receptor agonists enhance the autophagic activity of β‐cells, which might contribute to the profound effects of glucagon‐like peptide‐1 receptor agonists on systemic metabolism. In this review, the results from studies on the role of autophagy in β‐cells and their implication in the development of diabetes are discussed. In addition to non‐selective (macro)autophagy, the role and mechanisms of selective autophagy and other minor forms of autophagy that might occur in β‐cells are discussed. As β‐cell failure is the ultimate cause of diabetes and unresponsiveness to conventional therapy, modulation of β‐cell autophagy might represent a future antidiabetic treatment approach, particularly in patients who are not well managed with current antidiabetic therapy.

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Section: Mitophagy and Er‐phagy In β‐Cellsmentioning

confidence: 99%

Role of β‐cell autophagy in β‐cell physiology and the development of diabetes

Yasasilka,

Lee

2024

J of Diabetes Invest

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“…The poor elimination of damaged mitochondria led to mitochondrial dysfunction of pancreatic β cells, contributing to tacrolimus-induced β-cell dysfunction or glucose intolerance. 93 Another study in mice with tacrolimus-induced diabetes reported that tacrolimus-induced impaired mitochondrial oxygen consumption, decreased ATP production, and increased ROS production. A ginseng extract ameliorated this mitochondrial dysfunction and improved insulin secretion by reducing autophagosome formation and lysosomal degradation.…”

Section: Immunosuppressive Drugs and Autophagymentioning

confidence: 99%

Autophagy: A Silent Protagonist in Kidney Transplantation

Ponticelli,

Reggiani,

Moroni

2023

Transplantation

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Autophagy is a lysosome-dependent regulated mechanism that recycles unnecessary cytoplasmic components. It is now known that autophagy dysfunction may have a pathogenic role in several human diseases and conditions, including kidney transplantation. Both defective and excessive autophagy may induce or aggravate several complications of kidney transplantation, such as ischemia–reperfusion injury, alloimmune response, and immunosuppressive treatment and side effects. Although it is still complicated to measure autophagy levels in clinical practice, more attention should be paid to the factors that may influence autophagy. In kidney transplantation, the association of low doses of a mammalian target of rapamycin inhibitor with low doses of a calcineurin inhibitor may be of benefit for autophagy modulation. However, further studies are needed to explore the role of other autophagy regulators.

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