Effect of proinflammatory interleukins on jejunal nutrient transport

Hardin, James A.; Kroeker, Karen I.; Chung, Bonghoon; Gall, David

doi:10.1136/gut.47.2.184

Cited by 67 publications

(50 citation statements)

References 53 publications

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“…22 This is at variance to D-glucose, which uses SGLT-1 for absorption from the gut. 23 This finding supports the hypothesis that also in the present setting, as we had observed previously for LPSinduced shock, a specific D-glucose-SGLT-1 interaction is required to achieve protection from hepatic injury. Similarly, no protection from LPS/ D-GalN-induced liver injury is observed on oral administration of the disaccharide sucrose.…”

Section: Discussionsupporting

confidence: 93%

Intestinal Glucose Uptake Protects Liver from Lipopolysaccharide and d-Galactosamine, Acetaminophen, and Alpha-Amanitin in Mice

Zanobbio

Palazzo

Gariboldi

et al. 2009

The American Journal of Pathology

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Superiore di Sanità, Rome; and the Istituto Nazionale per lo Studio e la Cura dei Tumori, ‡ Milan, ItalyWe have recently observed that oral administration of D-glucose saves animals from lipopolysaccharide (LPS)-induced death. This effect is the likely consequence of glucose-induced activation of the sodiumdependent glucose transporter-1. In this study, we investigated possible hepatoprotective effects of glucose-induced, sodium-dependent, glucose transporter-1 activation. We show that oral administration of D-glucose , but not of either D-fructose or sucrose, prevents LPS-induced liver injury, as well as liver injury and death induced by an overdose of acetaminophen. In both of these models, physiological liver morphology is maintained and organ protection is confirmed by unchanged levels of the circulating markers of hepatotoxicity, such as alanine transaminase or lactate dehydrogenase. In addition, D-glucose was found to protect the liver from ␣-amanitin-induced liver injury. In this case, in contrast to the previously described models, a second signal had to be present in addition to glucose to achieve protective efficacy. Toll-like receptor 4 stimulation that was induced by low doses of LPS was identified as such a second signal. Eventually, the protective effect of orally administered glucose on liver injury induced by LPS, overdose of acetaminophen, or ␣-amanitin was shown to be mediated by the anti-inflammatory cytokine interleukin-10. Liver failure is one of the most devastating syndromes observed in clinical practice. It is associated with high overall mortality, ranging from 30% to 80%, depending on the underlying etiology. 1,2 The most common etiologies are acute viral hepatitis, drug overdose, idiosyncratic drug reactions, and ingestion of other toxins.3 Insulting agents can cause hepatocyte death through different mechanisms of action, and when the amount of functioning cells decreases to a level at which the organ is no longer capable of fulfilling its metabolic and synthetic tasks, hepatic failure takes place. 4 Recently we demonstrated, in a murine model of septic shock, that oral administration of D-glucose saves mice from death, most likely as a result of glucose-induced activation of the intestinal sodium-dependent glucose transporter-1 (SGLT-1).5 Using this model, we made preliminary observations that the liver, one of the organs most severely affected by lipopolysaccharide and D-galactosamine (LPS/D-GalN) treatment, was protected by oral administration of D-glucose. The expression of SGLT-1 on the apical membrane of enterocytes and the observation that protection from LPS shock was observed only on oral administration of D-glucose, but not on i.p. administration, suggested an important role of intestinal epithelial cells in protection from LPS-induced injury to the liver and other organs.Here, we report on a more extensive investigation on the hepatoprotective effect of orally administered D-glucose. Glucose was evaluated in LPS-induced shock, as well as in two other models of acute liver f...

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Section: Discussionsupporting

confidence: 93%

Intestinal Glucose Uptake Protects Liver from Lipopolysaccharide and d-Galactosamine, Acetaminophen, and Alpha-Amanitin in Mice

Zanobbio

Palazzo

Gariboldi

et al. 2009

The American Journal of Pathology

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“…In addition, Stouthard et al (40) studied patients with metastatic renal cell cancer receiving rhIL-6 infusion and observed an increase in glucose appearance and whole body glucose disposal when the isotopic tracer dilution method was used. In addition, Stouthard et al (39) demonstrated that IL-6 enhanced both basal and insulin-stimulated glucose uptake in cultured 3T3-L1 adipocytes, and Hardin et al (11) observed increased glucose transport in jejunal tissue incubated with IL-6 compared with controls. Therefore, a phasic increase in IL-6 may have an important biological role, as previously suggested (6,27).…”

Section: Discussionmentioning

confidence: 99%

Hepatosplanchnic clearance of interleukin-6 in humans during exercise

Febbraio

Ott

Nielsen

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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The cytokine interleukin (IL)-6 can increase markedly in the circulation during exercise, but whether the liver is a source of this increase is unknown. The aim of this study was to measure IL-6 flux across the hepatosplanchnic tissues in humans. To elevate systemic concentrations of IL-6, six healthy male subjects performed 120 min of semirecumbent cycling, and blood samples were simultaneously obtained from a brachial artery and the hepatic vein before and during exercise for the analysis of IL-6. Hepatosplanchnic blood flow (HBF) was measured using the indocyanine green infusion technique. Net hepatosplanchnic IL-6 balance was calculated from these measures. HBF was 1.3 ± 0.1 l/min at rest and was not reduced throughout exercise, averaging 1.1 ± 0.2 l/min. Arterial plasma IL-6 markedly increased ( P < 0.05) from 1.8 ± 0.6 ng/l at rest to 14.3 ± 3.2 ng/l after 120 min of exercise. The hepatosplanchnic viscera did not contribute to this increase, since there was a net hepatosplanchnic IL-6 uptake (0.8 ± 0.3 vs. 5.5 ± 1.9 ng/min, rest vs. 120 min; P < 0.05). These data demonstrate that the hepatosplanchnic viscera remove IL-6 from the circulation in humans. This removal may constitute a mechanism limiting the negative chronic metabolic action of chronically elevated circulating IL-6.

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“…These authors demonstrated that treating 3T3-L1 adipocytes with recombinant murine IL-6 for 5 h increased basal glucose transport by ~20%. An increase in IL-6-stimulated basal glucose transport has also been observed in both smooth muscle [67] and chondrocytes [68], although this effect is not always seen, as two studies have found no effect of IL-6 on basal glucose transport in 3T3 L1 adipocytes [55,69].…”

Section: Interaction Between Il-6 and Glucose Transport In Vitromentioning

confidence: 99%