Autophagy in Diabetes Pathophysiology: Oxidative Damage Screening as Potential for Therapeutic Management by Clinical Laboratory Methods

Nwose, Ezekiel Uba; Bwititi, Phillip

doi:10.3389/fcell.2021.651776

Cited by 5 publications

(3 citation statements)

References 60 publications

(87 reference statements)

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“…Previous reports ( 62 – 64 ) have demonstrated glucose mediated autophagy in neurons and renal cells. Autophagy is a key quality control mechanism known to maintain cellular integrity ( 65 , 66 ). In condition of hyperglycemia, mitochondrial depolarization, endoplasmic reticulum stress and miss folding of proteins leads to induction of autophagy, targeted to removal of miss folded proteins ( 67 ).…”

Section: Discussionmentioning

confidence: 99%

Spontaneous NETosis in diabetes: A role of hyperglycemia mediated ROS and autophagy

et al. 2023

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Type 2-diabetes, particularly poorly controlled diabetes, is a risk factor for several infections such as lower respiratory tract and skin infections. Hyperglycemia, a characteristic downstream effect of poorly controlled diabetes, has been shown to impair the function of immune cells, in particular neutrophils. Several studies have demonstrated that hyperglycemia-mediated priming of NADPH oxidase results in subsequent elevated levels of reactive oxygen species (ROS). In healthy neutrophils, ROS plays an important role in pathogen killing by phagocytosis and by induction of Neutrophil Extracellular Traps (NETs). Given the key role of ROS in autophagy, phagocytosis and NETosis, the relationship between these pathways and the role of diabetes in the modulation of these pathways has not been explored previously. Therefore, our study aimed to understand the relationship between autophagy, phagocytosis and NETosis in diabetes. We hypothesized that hyperglycemia-associated oxidative stress alters the balance between phagocytosis and NETosis by modulating autophagy. Using whole blood samples from individuals with and without type 2-diabetes (in the presence and absence of hyperglycemia), we demonstrated that (i) hyperglycemia results in elevated levels of ROS in neutrophils from those with diabetes, (ii) elevated levels of ROS increase LCIII (a marker for autophagy) and downstream NETosis. (iii) Diabetes was also found to be associated with low levels of phagocytosis and phagocytic killing of S. pneumoniae. (iv) Blocking either NADPH oxidase or cellular pathways upstream of autophagy led to a significant reduction in NETosis. This study is the first to demonstrate the role of ROS in altering NETosis and phagocytosis by modulating autophagy in type 2-diabetes.

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Section: Discussionmentioning

confidence: 99%

Spontaneous NETosis in diabetes: A role of hyperglycemia mediated ROS and autophagy

et al. 2023

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“…After fulfilling lactation mission, epithelial cells undergo programed cell death (L20). Cell–cell interaction analysis indicated that epithelial cells promoted the proliferation and differentiation of immune cells by secreting IL34 ligand and binding to CSF1R surface receptor [ 60 , 61 ]. This suggests that epithelial cells can be actively cleared by immune cells to eliminate dead cells under high intensity lactation.…”

Section: Discussionmentioning

confidence: 99%

A cell transcriptomic profile provides insights into adipocytes of porcine mammary gland across development

Fan,

Jin,

et al. 2023

J Animal Sci Biotechnol

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Background Studying the composition and developmental mechanisms in mammary gland is crucial for healthy growth of newborns. The mammary gland is inherently heterogeneous, and its physiological function dependents on the gene expression of multiple cell types. Most studies focused on epithelial cells, disregarding the role of neighboring adipocytes. Results Here, we constructed the largest transcriptomic dataset of porcine mammary gland cells thus far. The dataset captured 126,829 high-quality nuclei from physiological mammary glands across five developmental stages (d 90 of gestation, G90; d 0 after lactation, L0; d 20 after lactation, L20; 2 d post natural involution, PI2; 7 d post natural involution, PI7). Seven cell types were identified, including epithelial cells, adipocytes, endothelial cells, fibroblasts cells, immune cells, myoepithelial cells and precursor cells. Our data indicate that mammary glands at different developmental stages have distinct phenotypic and transcriptional signatures. During late gestation (G90), the differentiation and proliferation of adipocytes were inhibited. Meanwhile, partly epithelial cells were completely differentiated. Pseudo-time analysis showed that epithelial cells undergo three stages to achieve lactation, including cellular differentiation, hormone sensing, and metabolic activation. During lactation (L0 and L20), adipocytes area accounts for less than 0.5% of mammary glands. To maintain their own survival, the adipocyte exhibited a poorly differentiated state and a proliferative capacity. Epithelial cells initiate lactation upon hormonal stimulation. After fulfilling lactation mission, their undergo physiological death under high intensity lactation. Interestingly, the physiological dead cells seem to be actively cleared by immune cells via CCL21-ACKR4 pathway. This biological process may be an important mechanism for maintaining homeostasis of the mammary gland. During natural involution (PI2 and PI7), epithelial cell populations dedifferentiate into mesenchymal stem cells to maintain the lactation potential of mammary glands for the next lactation cycle. Conclusion The molecular mechanisms of dedifferentiation, proliferation and redifferentiation of adipocytes and epithelial cells were revealed from late pregnancy to natural involution. This cell transcriptomic profile constitutes an essential reference for future studies in the development and remodeling of the mammary gland at different stages.

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“…Besides, the dysregulation of autophagy could be used as a possible therapeutic target in DM [69]. Therefore, autophagy should be monitored at every disease stage of all target organs [70]. Understanding the role of autophagy in cellular maintenance is currently the focus of interest, with the help of various molecular laboratory techniques [71].…”

Section: Autophagymentioning

confidence: 99%

Autophagy and diabetes

Obradovic,

Zafirovic,

Gluvic

et al. 2023

Exploration of Medicine

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The current literature findings on autophagy’s beneficial and detrimental roles in diabetes mellitus (DM) and diabetes-related comorbidities were reviewed. The effects of oral hypoglycaemic medicines and autophagy in DM. Autophagy plays an important function in cellular homeostasis by promoting cell survival or initiating cell death in physiological settings was also assessed. Although autophagy protects insulin-target tissues, organelle failure caused by autophagy malfunction influences DM and other metabolic diseases. Endoplasmic reticulum and oxidative stress enhance autophagy levels, making it easier to regulate stress-induced intracellular changes. Evidence suggests that autophagy-caused cell death can occur when autophagy is overstimulated and constitutively activated, which might prevent or develop DM. Even though the precise role of autophagy in DM complications is uncertain, deregulation of the autophagic machinery is strongly linked to beta cell destruction and the aetiology of DM. Thus, improving autophagy dysfunction is a possible therapeutic objective in treating DM and other metabolic disorders.

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Autophagy in Diabetes Pathophysiology: Oxidative Damage Screening as Potential for Therapeutic Management by Clinical Laboratory Methods

Cited by 5 publications

References 60 publications

Spontaneous NETosis in diabetes: A role of hyperglycemia mediated ROS and autophagy

Spontaneous NETosis in diabetes: A role of hyperglycemia mediated ROS and autophagy

A cell transcriptomic profile provides insights into adipocytes of porcine mammary gland across development

Autophagy and diabetes

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