Dexamethasone enhances glucose uptake by SGLT1 and GLUT1 and boosts ATP generation through the PPP-TCA cycle in bovine neutrophils
- Author:
Xinbo WANG
1
;
Mingyu TANG
;
Yuming ZHANG
;
Yansong LI
;
Jingdong MAO
;
Qinghua DENG
;
Shusen LI
;
Zhenwei JIA
;
Liyin DU
Author Information
- Publication Type:Original Article
- From:Journal of Veterinary Science 2022;23(5):e76-
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 2+ /P 5+ 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.
