Dexamethasone enhances glucose uptake by SGLT1 and GLUT1 and boosts ATP generation through the PPP-TCA cycle in bovine neutrophils

Xinbo Wang; Mingyu Tang; Yuming Zhang; Yansong Li; Jingdong Mao; Qinghua Deng; Shusen Li; Zhenwei Jia; Liyin Du

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자료유형: 학술저널

저자정보: Xinbo Wang (Inner Mongolia Minzu University) Mingyu Tang (Inner Mongolia Minzu University) Yuming Zhang (Inner Mongolia Minzu University) Yansong Li (Inner Mongolia Minzu University) Jingdong Mao (Inner Mongolia Minzu University) Qinghua Deng (Inner Mongolia Minzu University) Shusen Li (Inner Mongolia Minzu University) Zhenwei Jia (Inner Mongolia Minzu University) Liyin Du (Inner Mongolia Minzu University)

저널정보: 대한수의학회 Journal of Veterinary Science Journal of Veterinary Science 제23권 제5호

발행연도: 2022.9

수록면: 109 - 122 (14page)

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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)-1β, IL-6 and tumor necrosis factor (TNF)-α 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 Ca<SUP>2+</SUP>/P<SUP>5+</SUP> ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1β, IL-6 and TNF-α levels. Particularly in neutrophils, DEX injection inhibited p65-NFκB 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.

#Neutrophils #Dexamethasone #Tricarboxylic Acid Cycle #Adenosine Triphosphate #Bovine

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