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Diminished nutrient supply stimulates endothelial metabolic rate turnover: impact of cellular sex on glucose and glutamine metabolism

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Item Type:Article
Title:Diminished nutrient supply stimulates endothelial metabolic rate turnover: impact of cellular sex on glucose and glutamine metabolism
Creators: Lorenz, Mario ORCID logoORCID: https://orcid.org/0000-0001-5267-4101, Wiebach, Janine ORCID logoORCID: https://orcid.org/0000-0002-7416-9859, Vietzke, Angelika, Bartsch, Cornelia, Stangl, Verena, Stangl, Karl, Henrich, Wolfgang, Kirwan, Jennifer A. ORCID logoORCID: https://orcid.org/0000-0002-5423-1651 and Fritsche-Guenther, Raphaela ORCID logoORCID: https://orcid.org/0000-0002-6965-0226
Abstract:Endothelial cells must be able to maintain metabolic activity during angiogenesis. At impaired energy levels, they have to formnew blood vessels to supply the surrounding tissue with oxygen and nutrients. This requires modifications of intracellular metab-olism to provide the necessary energy for migration and proliferation. Studies on metabolic adaptations of endothelial cells todiminished energy supply are sparse, and investigation of potential sex differences is lacking. We therefore performed a meta-bolic flux analysis with (13)C-glucose or (13)C-glutamine labeling at different time points with female and male human umbilical veinendothelial cells from dizygotic twin pairs. Labeling was performed under basal conditions and after serum starvation at earlyand late time points for each labeling. Overall, a much faster label incorporation was found in serum-starved cells. Central car-bon metabolites showed a significantly higher label incorporation at both early and late time points for (13)C-glucose and (13)C-glutamineafter serum starvation, independent of the sex of the cells. However, a nonsignificant but consistent sex-specific pattern wasobserved. After labeling with (13)C-glucose, a higher label incorporation was seen in male cells after serum starvation. In contrast, label-ing with 13C-glutamine resulted in a faster label incorporation in female cells, both at basal conditions and after serum starvation. Theobserved sex differences were coherent throughout the analyzed metabolites. Although not significant and rather small, they couldpoint to subtle sex differences in glucose vs. glutamine metabolism in cellular metabolic adaptations to reduced energy supply.
Keywords:Endothelial Metabolism, Fux Analysis, Glucose and Glutamine, Serum Starvation, Sex Differences
Source:American Journal of Physiology Cell Physiology
ISSN:0363-6143
Publisher:American Physiological Society
Volume:331
Number:6
Page Range:C1680-C1687
Date:December 2026
Official Publication:https://doi.org/10.1152/ajpcell.00336.2026
PubMed:View item in PubMed

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