β Cell and Autophagy: What Do We Know?

Mohammadi-Motlagh, Hamid-Reza; Sadeghalvad, Mona; Yavari, Niloofar; Primavera, Rosita; Soltani, Setareh; Chetty, Shashank; Ganguly, Abantika; Regmi, Shobha; Fløyel, Tina; Kaur, Simranjeet; Mirza, Aashiq H.; Thakor, Avnesh S.; Pociot, Flemming; Yarani, Reza

doi:10.3390/biom13040649

Cited by 6 publications

(3 citation statements)

References 205 publications

(279 reference statements)

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“…The latter then progressively results in a loss of membrane potential, and the subsequent formation of secondary necrotic cells, leading to the leakage of cellular constituents (Kim & Lee, 2010 ; Sachet et al, 2017 ), explaining the observed increase in proteins and other cell membrane constituents (Sachet et al, 2017 ), such as phospholipid derivatives (choline, myo-inositol (Chaurio et al, 2009 ) and glycan structural components (mannose, N-acetylglucosamine (Rapoport & Pendu, 1999 ) in these poorly controlled type 2 diabetes patients. In contrast to this, several studies have also reported hyperactivation of autophagy in type 2 diabetes patients, as a compensatory mechanism to recycle various cellular contents for the production of adenosine triphosphate during hypoglycemic/fasting states (Denton & Kumar, 2019 ; Mohammadi-Motlagh et al, 2023 ; Yang et al, 2017 ). Interestingly, it has also been suggested that the increased autophagy that occurs in diabetes patients β-cells may also be caused by metformin treatment (Jiang et al, 2014 ), and a secondary inhibition of mTORc1 (Blandino-Rosano et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Characterizing poorly controlled type 2 diabetes using 1H-NMR metabolomics

Theron,

Mason,

van Reenen

et al. 2024

Metabolomics

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Introduction The prevalence of type 2 diabetes has surged to epidemic proportions and despite treatment administration/adherence, some individuals experience poorly controlled diabetes. While existing literature explores metabolic changes in type 2 diabetes, understanding metabolic derangement in poorly controlled cases remains limited. Objective This investigation aimed to characterize the urine metabolome of poorly controlled type 2 diabetes in a South African cohort. Method Using an untargeted proton nuclear magnetic resonance metabolomics approach, urine samples from 15 poorly controlled type 2 diabetes patients and 25 healthy controls were analyzed and statistically compared to identify differentiating metabolites. Results The poorly controlled type 2 diabetes patients were characterized by elevated concentrations of various metabolites associated with changes to the macro-fuel pathways (including carbohydrate metabolism, ketogenesis, proteolysis, and the tricarboxylic acid cycle), autophagy and/or apoptosis, an uncontrolled diet, and kidney and liver damage. Conclusion These results indicate that inhibited cellular glucose uptake in poorly controlled type 2 diabetes significantly affects energy-producing pathways, leading to apoptosis and/or autophagy, ultimately contributing to kidney and mild liver damage. The study also suggests poor dietary compliance as a cause of the patient’s uncontrolled glycemic state. Collectively these findings offer a first-time comprehensive overview of urine metabolic changes in poorly controlled type 2 diabetes and its association with secondary diseases, offering potential insights for more targeted treatment strategies to prevent disease progression, treatment efficacy, and diet/treatment compliance.

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Section: Discussionmentioning

confidence: 99%

Characterizing poorly controlled type 2 diabetes using 1H-NMR metabolomics

Theron,

Mason,

van Reenen

et al. 2024

Metabolomics

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“…Drp1 also plays a critical role in the regulation of mitophagy as shown in Figure 2 , thus helping to maintain mitochondrial integrity and function necessary for cell survival [ 118 , 119 , 120 , 121 ]. Previous studies also demonstrated mitochondrial fission followed by selective fusion and elimination of dysfunctional mitochondria through mitophagy [ 71 ].…”

Section: Targeting Mitochondrial Dynamic Proteinsmentioning

confidence: 99%

Mitochondrial Dynamics and Insulin Secretion

Kabra,

Jastroch

2023

IJMS

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Mitochondria are involved in the regulation of cellular energy metabolism, calcium homeostasis, and apoptosis. For mitochondrial quality control, dynamic processes, such as mitochondrial fission and fusion, are necessary to maintain shape and function. Disturbances of mitochondrial dynamics lead to dysfunctional mitochondria, which contribute to the development and progression of numerous diseases, including Type 2 Diabetes (T2D). Compelling evidence has been put forward that mitochondrial dynamics play a significant role in the metabolism-secretion coupling of pancreatic β cells. The disruption of mitochondrial dynamics is linked to defects in energy production and increased apoptosis, ultimately impairing insulin secretion and β cell death. This review provides an overview of molecular mechanisms controlling mitochondrial dynamics, their dysfunction in pancreatic β cells, and pharmaceutical agents targeting mitochondrial dynamic proteins, such as mitochondrial division inhibitor-1 (mdivi-1), dynasore, P110, and 15-oxospiramilactone (S3).

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“…However, the lower‐than‐expected levels of β‐cell apoptosis in humans with T2DM 9 suggest a role for alternative mechanisms that impair β‐cell function but spare these cells from apoptotic‐driven death. While impaired β‐cell autophagy can be considered one option, 10 the current text will focus predominantly on the dedifferentiation of β‐cells, with a focus on modulating the inherent plasticity of islet cells as an approach to preserve or enhance functional β‐cell mass in diabetes.…”

Section: Introduction: the Scope Of The Reviewmentioning

confidence: 99%

Pancreatic islet cell plasticity: Pathogenic or therapeutically exploitable?

Tanday,

Tarasov,

Moffett

et al. 2023

Diabetes Obesity Metabolism

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The development of pancreatic islet endocrine cells is a tightly regulated process leading to the generation of distinct cell types harbouring different hormones in response to small changes in environmental stimuli. Cell differentiation is driven by transcription factors that are also critical for the maintenance of the mature islet cell phenotype. Alteration of the insulin‐secreting β‐cell transcription factor set by prolonged metabolic stress, associated with the pathogenesis of diabetes, obesity or pregnancy, results in the loss of β‐cell identity through de‐ or transdifferentiation. Importantly, the glucose‐lowering effects of approved and experimental antidiabetic agents, including glucagon‐like peptide‐1 mimetics, novel peptides and small molecules, have been associated with preventing or reversing β‐cell dedifferentiation or promoting the transdifferentiation of non‐β‐cells towards an insulin‐positive β‐cell‐like phenotype. Therefore, we review the manifestations of islet cell plasticity in various experimental settings and discuss the physiological and therapeutic sides of this phenomenon, focusing on strategies for preventing β‐cell loss or generating new β‐cells in diabetes. A better understanding of the molecular mechanisms underpinning islet cell plasticity is a prerequisite for more targeted therapies to help prevent β‐cell decline in diabetes.

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β Cell and Autophagy: What Do We Know?

Cited by 6 publications

References 205 publications

Characterizing poorly controlled type 2 diabetes using 1H-NMR metabolomics

Characterizing poorly controlled type 2 diabetes using 1H-NMR metabolomics

Mitochondrial Dynamics and Insulin Secretion

Pancreatic islet cell plasticity: Pathogenic or therapeutically exploitable?

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