Current Status of Autophagy Enhancers in Metabolic Disorders and Other Diseases

Park, Kihyoun; Lee, Myung-Shik

doi:10.3389/fcell.2022.811701

Cited by 9 publications

(11 citation statements)

References 244 publications

(276 reference statements)

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“…[93][94][95][96][97][98] Thus, the suppression of hyperactive mTORC1 by TZDs may account for their apparent insulin-sensitising activity, resulting in glycaemic control while suppressing insulin secretion. Also, the suppression of hyperactive mTORC1 by TZDs may drive cardio-renal and beta-cell autophagy and mitophagy, 99 thereby counteracting diabetic cardiomyopathy, nephropathy and beta-cell failure. Also, the suppression of hyperactive mTORC1 by TZDs may account for their pleiotropic activities beyond the diabetic context, resulting in alleviating hepatic steatosis, blood pressure, dyslipidemia, inflammatory biomarkers, endothelial damage, a variety of cancer types, neurodegeneration and ageing.…”

Section: Pparg Activation By Tzds Results In Transcriptional Activati...mentioning

confidence: 99%

TorS ‐ Reframing a rational for type 2 diabetes treatment

Bar‐Tana

2023

Diabetes Metabolism Res

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The mammalian target of rapamycin complex 1 syndrome (Tors), paradigm implies an exhaustive cohesive disease entity driven by a hyperactive mTORC1, and which includes obesity, type 2 diabetic hyperglycemia, diabetic dyslipidemia, diabetic cardiomyopathy, diabetic nephropathy, diabetic peripheral neuropathy, hypertension, atherosclerotic cardiovascular disease, non‐alcoholic fatty liver disease, some cancers, neurodegeneration, polycystic ovary syndrome, psoriasis and other. The TorS paradigm may account for the efficacy of standard‐of‐care treatments of type 2 diabetes (T2D) in alleviating the glycaemic and non‐glycaemic diseases of TorS in T2D and non‐T2D patients. The TorS paradigm may generate novel treatments for TorS diseases.

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Section: Pparg Activation By Tzds Results In Transcriptional Activati...mentioning

confidence: 99%

TorS ‐ Reframing a rational for type 2 diabetes treatment

Bar‐Tana

2023

Diabetes Metabolism Res

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“…Several groups have developed such autophagy modulators, and studied the effects of novel agents or known drugs, such as berberine, imatinib, MSL‐7, rapamycin, resveratrol, spermidine, trehalose, rosiglitazone or fenofibrate, on β‐cell autophagy and diabetes. Readers are encouraged to consult recent reviews 69 . In the present review, the role of autophagy in the effects of known drugs that are already used for treating metabolic disorders and diabetes is discussed.…”

Section: Antidiabetic Drugs and β‐Cell Autophagymentioning

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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“…Since autophagy controls intracellular nutrient homeostasis and the integrity of organelles that are critical for energy balances, dysregulation of autophagy is likely to contribute to the pathogenesis of metabolic disorders. Hence, changes of autophagy in metabolic tissues have been extensively studied in metabolic diseases 37 , 38 . Previous studies have reported that autophagy can protect pancreatic β-cells against metabolic stress, such as palmitic acid (PA)-induced lipotoxicity, in vitro 39 , 40 .…”

Section: Autophagy Of Pancreatic β-Cellsmentioning

confidence: 99%

Pancreatic β-cell mitophagy as an adaptive response to metabolic stress and the underlying mechanism that involves lysosomal Ca2+ release

Oh,

Park,

Sonn

et al. 2023

Exp Mol Med

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Mitophagy is an excellent example of selective autophagy that eliminates damaged or dysfunctional mitochondria, and it is crucial for the maintenance of mitochondrial integrity and function. The critical roles of autophagy in pancreatic β-cell structure and function have been clearly shown. Furthermore, morphological abnormalities and decreased function of mitochondria have been observed in autophagy-deficient β-cells, suggesting the importance of β-cell mitophagy. However, the role of authentic mitophagy in β-cell function has not been clearly demonstrated, as mice with pancreatic β-cell-specific disruption of Parkin, one of the most important players in mitophagy, did not exhibit apparent abnormalities in β-cell function or glucose homeostasis. Instead, the role of mitophagy in pancreatic β-cells has been investigated using β-cell-specific Tfeb-knockout mice (TfebΔβ-cell mice); Tfeb is a master regulator of lysosomal biogenesis or autophagy gene expression and participates in mitophagy. TfebΔβ-cell mice were unable to adaptively increase mitophagy or mitochondrial complex activity in response to high-fat diet (HFD)-induced metabolic stress. Consequently, TfebΔβ-cell mice exhibited impaired β-cell responses and further exacerbated metabolic deterioration after HFD feeding. TFEB was activated by mitochondrial or metabolic stress-induced lysosomal Ca2+ release, which led to calcineurin activation and mitophagy. After lysosomal Ca2+ release, depleted lysosomal Ca2+ stores were replenished by ER Ca2+ through ER→lysosomal Ca2+ refilling, which supplemented the low lysosomal Ca2+ capacity. The importance of mitophagy in β-cell function was also demonstrated in mice that developed β-cell dysfunction and glucose intolerance after treatment with a calcineurin inhibitor that hampered TFEB activation and mitophagy.

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Current Status of Autophagy Enhancers in Metabolic Disorders and Other Diseases

Cited by 9 publications

References 244 publications

TorS ‐ Reframing a rational for type 2 diabetes treatment

TorS ‐ Reframing a rational for type 2 diabetes treatment

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

Pancreatic β-cell mitophagy as an adaptive response to metabolic stress and the underlying mechanism that involves lysosomal Ca2+ release

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