Saccharin and Sucralose Protect the Glomerular Microvasculature In Vitro against VEGF-Induced Permeability
Diabetic kidney disease (DKD) has become a global health concern, with about 40% of people living with type 1 and type 2 diabetes mellitus developing DKD. Upregulation of vascular endothelial growth factor (VEGF) in the kidney is a significant pathology of DKD associated with increased glomerular va...
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doaj-a510323b031342c9b7b8d05357f9bb902021-08-26T14:10:47ZengMDPI AGNutrients2072-66432021-08-01132746274610.3390/nu13082746Saccharin and Sucralose Protect the Glomerular Microvasculature In Vitro against VEGF-Induced PermeabilityEmmanuella Enuwosa0Lata Gautam1Linda King2Havovi Chichger3Biomedical Research Group, Faculty of Science & Engineering, School of Life Sciences, Anglia Ruskin University, Cambridge CB1 1PT, UKForensic Science Research Group, Faculty of Science & Engineering, School of Life Sciences, Anglia Ruskin University, Cambridge CB1 1PT, UKBiomedical Research Group, Faculty of Science & Engineering, School of Life Sciences, Anglia Ruskin University, Cambridge CB1 1PT, UKBiomedical Research Group, Faculty of Science & Engineering, School of Life Sciences, Anglia Ruskin University, Cambridge CB1 1PT, UKDiabetic kidney disease (DKD) has become a global health concern, with about 40% of people living with type 1 and type 2 diabetes mellitus developing DKD. Upregulation of vascular endothelial growth factor (VEGF) in the kidney is a significant pathology of DKD associated with increased glomerular vascular permeability. To date, however, current anti-VEGF therapies have demonstrated limited success in treating DKD. Recent studies have shown that artificial sweeteners exhibit anti-VEGF potential. The aim of this study was therefore to assess the effects of aspartame, saccharin, and sucralose on VEGF-induced leak using an in vitro model of the glomerular endothelium. Saccharin and sucralose but not aspartame protected against VEGF-induced permeability. Whilst the sweeteners had no effect on traditional VEGF signalling, GC-MS analysis demonstrated that the sweetener sucralose was not able to enter the glomerular endothelial cell to exert the protective effect. Chemical and molecular inhibition studies demonstrated that sweetener-mediated protection of the glomerular endothelium against VEGF is dependent on the sweet taste receptor, T1R3. These studies demonstrate the potential for sweeteners to exert a protective effect against VEGF-induced increased permeability to maintain a healthy endothelium and protect against vascular leak in the glomerulus in settings of DKD.https://www.mdpi.com/2072-6643/13/8/2746artificial sweetenersdiabetic kidney diseasesweet taste receptorglomerularendotheliumvascular endothelial growth factor (VEGF) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Emmanuella Enuwosa Lata Gautam Linda King Havovi Chichger |
spellingShingle |
Emmanuella Enuwosa Lata Gautam Linda King Havovi Chichger Saccharin and Sucralose Protect the Glomerular Microvasculature In Vitro against VEGF-Induced Permeability Nutrients artificial sweeteners diabetic kidney disease sweet taste receptor glomerular endothelium vascular endothelial growth factor (VEGF) |
author_facet |
Emmanuella Enuwosa Lata Gautam Linda King Havovi Chichger |
author_sort |
Emmanuella Enuwosa |
title |
Saccharin and Sucralose Protect the Glomerular Microvasculature In Vitro against VEGF-Induced Permeability |
title_short |
Saccharin and Sucralose Protect the Glomerular Microvasculature In Vitro against VEGF-Induced Permeability |
title_full |
Saccharin and Sucralose Protect the Glomerular Microvasculature In Vitro against VEGF-Induced Permeability |
title_fullStr |
Saccharin and Sucralose Protect the Glomerular Microvasculature In Vitro against VEGF-Induced Permeability |
title_full_unstemmed |
Saccharin and Sucralose Protect the Glomerular Microvasculature In Vitro against VEGF-Induced Permeability |
title_sort |
saccharin and sucralose protect the glomerular microvasculature in vitro against vegf-induced permeability |
publisher |
MDPI AG |
series |
Nutrients |
issn |
2072-6643 |
publishDate |
2021-08-01 |
description |
Diabetic kidney disease (DKD) has become a global health concern, with about 40% of people living with type 1 and type 2 diabetes mellitus developing DKD. Upregulation of vascular endothelial growth factor (VEGF) in the kidney is a significant pathology of DKD associated with increased glomerular vascular permeability. To date, however, current anti-VEGF therapies have demonstrated limited success in treating DKD. Recent studies have shown that artificial sweeteners exhibit anti-VEGF potential. The aim of this study was therefore to assess the effects of aspartame, saccharin, and sucralose on VEGF-induced leak using an in vitro model of the glomerular endothelium. Saccharin and sucralose but not aspartame protected against VEGF-induced permeability. Whilst the sweeteners had no effect on traditional VEGF signalling, GC-MS analysis demonstrated that the sweetener sucralose was not able to enter the glomerular endothelial cell to exert the protective effect. Chemical and molecular inhibition studies demonstrated that sweetener-mediated protection of the glomerular endothelium against VEGF is dependent on the sweet taste receptor, T1R3. These studies demonstrate the potential for sweeteners to exert a protective effect against VEGF-induced increased permeability to maintain a healthy endothelium and protect against vascular leak in the glomerulus in settings of DKD. |
topic |
artificial sweeteners diabetic kidney disease sweet taste receptor glomerular endothelium vascular endothelial growth factor (VEGF) |
url |
https://www.mdpi.com/2072-6643/13/8/2746 |
work_keys_str_mv |
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