Glucose-mediated cytoprotection in the gut epithelium under ischemic and hypoxic stress
Chung-Yen Huang, Yu-Chen Pai and Linda Chia-Hui Yu
Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan ROC
Offprint requests to: Linda Chia-Hui Yu, Professor, Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan R.O.C. Suite 1020, #1 Jen-Ai Rd. Sec. I, Taipei 100, Taiwan R.O.C. e-mail: lchyu@ntu.edu.tw
Summary. Single-layered intestinal epithelia play key roles in the maintenance of gut homeostasis and barrier integrity. Various types of epithelial cell death, including apoptosis, necrosis, and necroptosis, have been detected in ischemic and hypoxic stress conditions, thus resulting in bacterial translocation and gut-derived septic complications. Cytoprotective strategies, such as enteral glucose uptake, rescue intestinal epithelium from cell death after ischemic and hypoxic injury. Although glucose metabolism and energy production are generally considered to be the key factors in cytoprotection, the precise modes and sites of action have not been clarified. Our recent studies have demonstrated that energy restoration promotes crypt hyperplasia but does not prevent epithelial cell death under ischemic stress. On the other hand, glycolytic pyruvate prevents epithelial cells from undergoing apoptosis and necroptosis by scavenging free radicals in an ATP-independent manner. Distinct gut protective mechanisms involving ATP, pyruvate, glucose metabolic enzymes, and sodium-dependent glucose transporter activation are discussed here. Overall, glucose-mediated cytoprotection may be a universal mechanism that has evolved in epithelial cells for the maintenance of intestinal homeostasis. Enteral glucose supplementation is beneficial as a perioperative supportive therapy for the protection of gut barrier integrity. Histol Histopathol 32, 543-550 (2017)
Key words: Ischemia/reperfusion, Hypoxia, Intestinal epithelium, Barrier function, Glucose metabolism, Cell death
DOI: 10.14670/HH-11-839