Cellular redox, maintained by the glutathione (GSH)- and thioredoxin (Trx)-dependent systems, has been implicated in the regulation of a variety of biological processes. The redox state of the GSH system becomes oxidized when cells are induced to differentiate by chemical agents. The aim of this study was to determine the redox state of cellular GSH/glutathione disulfide (GSH/GSSG) and Trx as a consequence of progression from proliferation to contact inhibition and spontaneous differentiation in colon carcinoma (Caco-2) cells. Results showed a significant decrease in GSH concentration, accompanied by a 40-mV oxidation of the cellular GSH/GSSG redox state and a 28-mV oxidation of the extracellular cysteine/cystine redox state in association with confluency and increase in differentiation markers. The redox state of Trx did not change. Thus the two central cellular antioxidant and redox-regulating systems (GSH and Trx) were independently controlled. According to the Nernst equation, a 30-mV oxidation is associated with a 10-fold change in the reduced/oxidized ratio of a redox-sensitive dithiol motif. Therefore, the measured 40-mV oxidation of the cellular GSH/GSSG couple or the 28-mV oxidation of the extracellular cysteine/cystine couple should be sufficient to function in signaling or regulation of differentiation in Caco-2 cells.

Leptin, a peptide encoded by the obese (ob) gene, is primarily secreted by adipocytes and is a critical hormone that controls body weight due to its central effects. Recently, additional roles for leptin in the gastrointestinal tract have been suggested because gastric lining cells also produce and release leptin in response to meal-related stimuli. While gastric epithelia might thus directly contribute to circulating leptin following a meal, here we show that inflamed colonic epithelial cells express and release leptin apically into the intestinal lumen. In addition, we demonstrate leptin expression and secretion in vitro in epithelial cells. In response to luminal leptin, model intestinal epithelia critically activate the NF-kappaB, a key signaling system to pro-inflammatory stimuli. The inflammatory effect of luminal leptin was characterized in vivo in mice administered intrarectal leptin. Leptin induced epithelial wall damage and neutrophil infiltration that represent characteristic histological findings in acute intestinal inflammation. These observations provide evidence for an intraluminal biological signaling of leptin and a new pathophysiological role for intraluminal leptin during states of intestinal inflammation such as inflammatory bowel disease.

Gut adaptation in SBS patients does not appear to involve an increase in gut-mucosal crypt depth or villus size. PepT1 is abundant along the small-bowel brush border in humans; expression in the colon indicates that the large intestine has a mechanism for luminal di- and tripeptide transport. Up-regulation of colonic PepT1 in SBS may adaptively improve accrual of malabsorbed di- and tripeptides, independent of changes in the mucosal surface area.

Hypothesis: Circulating ghrelin, produced primarily in the stomach, is a powerful orexigen. Ghrelin levels are elevated in states of hunger, but rapidly decline postprandially. Early alterations in ghrelin levels in morbidly obese patients undergoing weight reduction surgery may be attributed to gastric partitioning. Design and Patients: Thirty-four patients underwent Roux-en-Y gastric bypass with a completely divided gastroplasty to create a 15-mL vertically oriented gastric pouch. Eight other patients underwent other gastric procedures that did not involve complete division of the stomach, including 4 vertical banded gastroplasties and 4 antireflux surgical procedures. Six additional patients undergoing antireflux surgery served as lean control subjects. Plasma samples were obtained before surgery and immediately after surgery. In a substudy, plasma was collected after Rouxen-Y limb formation and after dividing the stomach to identify any changes in plasma ghrelin levels. Setting: Tertiary university medical center. Main Outcome Measures: Ghrelin levels at different stages of surgical intervention.