Hypoxia differentially regulates nutrient transport in rat jejunum regardless of luminal nutrient present

Abstract

nutrition and poor intestinal perfusion are hypothesized to play an important pathogenic role in nonocclusive small bowel necrosis. This study tests the hypothesis that glucose and glutamine transport are differentially regulated during hypoxia regardless of the luminal nutrient present. Sprague-Dawley rats (247 Ϯ 3 g; n ϭ 16) were randomized to receive 1 h of intestinal hypoxia or serve as normoxic controls. During this hour, jejunal loops were randomized to receive in situ perfusions of mannitol, glucose, or glutamine. When compared with normoxic groups, glucose but not glutamine transport was impaired (P Ͻ 0.001) during hypoxia. Messenger RNA abundance of the sodium glucose cotransporter sodium-dependent glucose cotransporter-1 (SGLT-1) and neutral basic amino acid transporter B o did not differ with hypoxia or nutrient perfused. Jejunal brush-border SGLT-1 abundance was decreased (P ϭ 0.039) with hypoxia; however, total cellular SGLT-1 protein abundance did not differ among treatment groups. These data indicate that SGLT-1 activity is regulated during hypoxia at the posttranslational level. Additional information regarding the mechanisms regulating nutrient transport in the hypoperfused intestine is critical for optimizing the composition of enteral nutrient formulas.sodium-dependent glucose cotransporter-1; nutrient absorption; small intestine THE INCIDENCE OF NONOCCLUSIVE small bowel necrosis is significant in traumatically injured patients, despite adequate systemic resuscitation. Currently, the causative mechanism remains unknown; however, enteral nutrition has been provided in ϳ90% of cases (21), suggesting that the inappropriate administration of specific nutrients into a poorly perfused small bowel may play a pathogenic role (12,21,23,25). During states of low blood flow to the intestine, enteral nutrients may increase oxygen demand beyond that available, potentially increasing intestinal hypoxia and impairing intestinal function. Gastrointestinal function has been shown to be impaired during hypoperfusion or decreased oxygenation of the intestine (28). Previous in vivo rat studies from our lab indicate that, during hypoperfusion, impaired barrier function, increased lactate concentration, decreased ATP concentration, and altered nutrient transport are characteristic (15). The detrimental effects of hypoperfusion may be minimized with an enteral formula composed of nutrients easily processed by the hypoperfused intestine.The purpose of the current study was to determine how nutrient perfusion alters sodium-dependent glucose and glutamine transport activity and their regulation at the cellular level during hypoperfusion. Glutamine transport occurs via system B o , which is part of a family of transporters for neutral amino acids (14). Glucose transport occurs via the sodium-glucose cotransporter [sodium-dependent glucose cotransporter-1 (SGLT-1)]. We previously reported that, during hypoxia, brush-border glucose transport is impaired, but glutamine transport remains unaltered following luminal perfusio...

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“…In aquatic animals, feeding may cease at very low oxygen tensions (Bernatis et al 2007) and hypoxia may slow digestive processing (Jordan and Steffensen 2007;McGaw 2008). Hypoxia has been shown to reduce assimilation efficiency in fish (Zhou et al 2001), while in mammals hypoxia-induced inhibition of the absorption of nutrients such as amino acids (Nelson et al 2003) and glucose (Kles and Tappenden 2002;Schoots et al 2006) has been described.…”

Molecular Mechanisms of Pharmaconutrients

“…Under catabolic conditions, such as sepsis and shock, release of glutamine from muscle tissue serves as a `stress signal' to the organism that leads to gene activation to promote cellular protection and immune regulation [6]. Glutamine is the preferred fuel source for the enterocyte and has been shown to preferentially be absorbed over glucose in settings of gut ischemia [7]. The small intestine is the principal site for glutamine absorption and occurs across the brush border via the epithelial sodium-dependent, neutral amino acid transport system B (ATB ○ ) and to a lesser extent via the sodium-independent, neutral amino acid transport system L [8].…”