KMID : 0893420220230050076
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Journal of Veterinary Science 2022 Volume.23 No. 5 p.76 ~ p.76
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Dexamethasone enhances glucose uptake by SGLT1 and GLUT1 and boosts ATP generation through the PPP-TCA cycle in bovine neutrophils
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Xinbo Wang
Mingyu Tang Yuming Zhang Yansong Li Jingdong Mao Qinghua Deng Shusen Li Zhenwei Jia Liyin Du
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Abstract
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Background : Clinical dexamethasone (DEX) treatment or stress in bovines results in extensive physiological changes with prominent hyperglycemia and neutrophils dysfunction.
Objectives : To elucidate the effects of DEX treatment in vivo on cellular energy status and the underlying mechanism in circulating neutrophils.
Methods : We selected eight-month-old male bovines and injected DEX for 3 consecutive days (1 time/d). The levels of glucose, total protein (TP), total cholesterol (TC), and the proinflammatory cytokines interleukin (IL)-1¥â, IL-6 and tumor necrosis factor (TNF)-¥á in blood were examined, and we then detected glycogen and adenosine triphosphate (ATP) content, phosphofructosekinase-1 (PFK1) and glucose-6-phosphate dehydrogenase (G6PDH) activity, glucose transporter (GLUT)1, GLUT4, sodium/glucose cotransporter (SGLT)1 and citrate synthase (CS) protein expression and autophagy levels in circulating neutrophils.
Results : DEX injection markedly increased blood glucose, TP and TC levels, the Ca2+/P5+ ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1¥â, IL-6 and TNF-¥á levels. Particularly in neutrophils, DEX injection inhibited p65-NF¥êB activation and elevated glycogen and ATP contents and SGLT1, GLUT1 and GR expression while inhibiting PFK1 activity, enhancing G6PDH activity and CS expression and lowering cell autophagy levels.
Conclusions : DEX induced neutrophils glucose uptake by enhancing SGLT1 and GLUT1 expression and the transformation of energy metabolism from glycolysis to pentose phosphate pathway (PPP)-tricarboxylic acid (TCA) cycle. This finding gives us a new perspective on deeper understanding of clinical anti-inflammatory effects of DEX on bovine.
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KEYWORD
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Neutrophils, Dexamethasone, Tricarboxylic Acid Cycle, Adenosine Triphosphate, Bovine
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