Dynamic glucose uptake, storage, and release by human microvascular endothelial cells

Yazdani, Samaneh; Bilan, Philip J.; Jaldín-Fincati, Javier R.; Pang, Janice; Ceban, Felicia; Saran, Ekambir; Brumell, John H.; Freeman, Spencer A.; Klip, Amira

doi:10.1091/mbc.e22-04-0146

Cited by 6 publications

(14 citation statements)

References 67 publications

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“…One potential pathway could involve the hydrolysis of glycogen by glycogen phosphorylase, which generates glucose 1-phosphate (G1P) that continues to fuel glycolysis by the enzyme phosphoglucomutase, which converts G1P to G6P [ 36 ]. HRECs are known to possess glycogen stores, which serve as an energy reserve during periods of high energy demand or limited nutrient availability, such as hypoxia or nutrient deprivation [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

“…Among the 12 members of the Glut family, microvascular endothelial cells primarily express Glut1 and Glut3, with lower expression levels of Gluts 6 and 10. HRECs do not express glucose transporters from the Na+-glucose–linked transporter (SGLT) family, suggesting that glucose enters HRECs mainly through Glut1 and Glut3 [ 37 ]. However, our findings indicate that inhibiting Glut1/3 in HRECs did not significantly affect their behavior, except at higher concentrations and with prolonged exposure, suggesting the presence of parallel routes for glucose entry into HRECs.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have highlighted Glut6 as a lysosomal glucose transporter involved in transporting glucose from lysosomes into the cytosol [ 41 ]. Notably, microvascular endothelial cells express Glut6, although at lower levels compared to Glut1 and Glut3 [ 37 ]. Another mechanism explaining the adaptation of HRECs to Glut1/3 inhibition is that around 20% of glucose taken up by the cells is incorporated into glycogen [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

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Upper glycolytic components contribute differently in controlling retinal vascular endothelial cellular behavior: Implications for endothelial-related retinal diseases

Oska,

Eltanani,

Shawky

et al. 2023

PLoS ONE

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Background Retinal degenerative diseases such as diabetic retinopathy and diabetic macular edema are characterized by impaired retinal endothelial cells (RECs) functionality. While the role of glycolysis in glucose homeostasis is well-established, its contributions to REC barrier assembly and cell spreading remain poorly understood. This study aimed to investigate the importance of upper glycolytic components in regulating the behavior of human RECs (HRECs). Methods Electric cell-substrate impedance sensing (ECIS) technology was employed to analyze the real-time impact of various upper glycolytic components on maintaining barrier functionality and cell spreading of HRECs by measuring cell resistance and capacitance, respectively. Specific inhibitors were used: WZB117 to inhibit Glut1/3, lonidamine to inhibit hexokinases, PFK158 to inhibit the PFKFB3-PFK axis, and TDZD-8 to inhibit aldolases. Additionally, the viability of HRECs was evaluated using the lactate dehydrogenase (LDH) cytotoxicity assay. Results The most significant reduction in electrical resistance and increase in capacitance of HRECs resulted from the dose-dependent inhibition of PFKFB3/PFK using PFK158, followed by aldolase inhibition using TDZD-8. LDH level analysis at 24- and 48-hours post-treatment with PFK158 (1 μM) or TDZD-8 (1 and 10 μM) showed no significant difference compared to the control, indicating that the disruption of HRECs functionality was not attributed to cell death. Conversely, inhibiting Glut1/3 with WZB117 had minimal impact on HREC behavior, except at higher concentrations (10 μM) and prolonged exposure. Lastly, inhibiting hexokinase with lonidamine did not noticeably alter HREC cell behavior. Conclusion This study illustrates the unique impacts of components within upper glycolysis on HREC functionality, emphasizing the crucial role of the PFKFB3/PFK axis in regulating HREC behavior. Understanding the specific contributions of each glycolytic component in preserving normal REC functionality will facilitate the development of targeted interventions for treating endothelial cell dysfunction in retinal disorders while minimizing effects on healthy cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Upper glycolytic components contribute differently in controlling retinal vascular endothelial cellular behavior: Implications for endothelial-related retinal diseases

Oska,

Eltanani,

Shawky

et al. 2023

PLoS ONE

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“…There are clearly transporters that support the exit of glucose from cells, but these remain to be identified in phagocytes. A recent study established that GLUT3 (SLC2A3) may provide a route for the transport of glucose out of endothelial cells 91 ; GLUT1 has also been implicated 92,93 . In epithelial cells, GLUT1 and GLUT2 are speculated to provide a route of efflux 94,95 .…”

Section: Solute Effluxmentioning

confidence: 99%

“…92,93 In epithelial cells, GLUT1 and GLUT2 are speculated to provide a route of efflux. 94,95 An additional route of release involves the dephosphorylation and transport of glucose into the ER 91,96 which is then released via an unknown mechanism. Whether or not GLUTs or the ER route of glucose exit could do the same in myeloid cells or in non-professional phagocyte populations remains to be tested but is an important line of future investigation.…”

Section: Polysaccharides and Monosaccharidesmentioning

confidence: 99%

The resolution of phagosomes

Mylvaganam

Freeman

2023

Immunological Reviews

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SummaryPhagocytosis is a fundamental immunobiological process responsible for the removal of harmful particulates. While the number of phagocytic events achieved by a single phagocyte can be remarkable, exceeding hundreds per day, the same phagocytic cells are relatively long‐lived. It should therefore be obvious that phagocytic meals must be resolved in order to maintain the responsiveness of the phagocyte and to avoid storage defects. In this article, we discuss the mechanisms involved in the resolution process, including solute transport pathways and membrane traffic. We describe how products liberated in phagolysosomes support phagocyte metabolism and the immune response. We also speculate on mechanisms involved in the redistribution of phagosomal metabolites back to circulation. Finally, we highlight the pathologies owed to impaired phagosome resolution, which range from storage disorders to neurodegenerative diseases.

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Endothelial metabolic control of insulin sensitivity through resident macrophages

Zhang,

Sjøberg,

Gong

et al. 2024

Cell Metabolism

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Dynamic glucose uptake, storage, and release by human microvascular endothelial cells

Cited by 6 publications

References 67 publications

Upper glycolytic components contribute differently in controlling retinal vascular endothelial cellular behavior: Implications for endothelial-related retinal diseases

Upper glycolytic components contribute differently in controlling retinal vascular endothelial cellular behavior: Implications for endothelial-related retinal diseases

The resolution of phagosomes

Endothelial metabolic control of insulin sensitivity through resident macrophages

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