American journal of physiology. Gastrointestinal and liver physiology
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Am. J. Physiol. Gastrointest. Liver Physiol. · May 2013
BMP2 inhibits TGF-β-induced pancreatic stellate cell activation and extracellular matrix formation.
Activation of pancreatic stellate cells (PSCs) by transforming growth factor (TGF)-β is the key step in the development of pancreatic fibrosis, a common pathological feature of chronic pancreatitis (CP). Bone morphogenetic proteins (BMPs), members of the TGF-β superfamily, have anti-fibrogenic functions, in contrast to TGF-β, in the kidney, lung, and liver. However, it is not known whether BMPs have an anti-fibrogenic role in the pancreas. ⋯ BMP2 pretreatment inhibited TGF-β-induced α-SMA, fibronectin, and collagen type Ia expression. Knocking down Smad1 with small-interfering RNA reversed the inhibitory effect of BMP2 on TGF-β-induced α-SMA and fibronectin expression. Thus, BMP2 opposes the fibrogenic function of TGF-β in PSCs through the Smad1 signaling pathway.
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Am. J. Physiol. Gastrointest. Liver Physiol. · May 2013
Neonatal colonic inflammation sensitizes voltage-gated Na(+) channels via upregulation of cystathionine β-synthetase expression in rat primary sensory neurons.
The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood, and treatment remains difficult. We have previously reported that colon-specific dorsal root ganglion (DRG) neurons were hyperactive in a rat model of IBS induced by neonatal colonic inflammation (NCI). This study was designed to examine plasticity of voltage-gated Na(+) channel activities and roles for the endogenous hydrogen sulfide-producing enzyme cystathionine β-synthetase (CBS) in chronic visceral hyperalgesia. ⋯ Administration of O-(carboxymethyl)hydroxylamine hemihydrochloride (AOAA), an inhibitor for CBS, remarkably suppressed Na(+) current density and reduced expression of Na(V)1.7 and Na(V)1.8. More importantly, intraperitoneal or intrathecal application of AOAA attenuated AWR scores in NCI rats in a dose-dependent manner. These data suggest that NCI enhances Na(+) channel activity of colon DRG neurons, which is most likely mediated by upregulation of CBS expression, thus identifying a potential target for treatment for chronic visceral pain in patients with IBS.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Apr 2013
Comparative StudySex differences in brain response to anticipated and experienced visceral pain in healthy subjects.
Women demonstrate higher pain sensitivity and prevalence of chronic visceral pain conditions such as functional gastrointestinal disorders than men. The role of sex differences in the brain processing of visceral pain is still unclear. In 16 male and 16 female healthy subjects we compared personality, anxiety levels, skin conductance response (SCR), and brain processing using functional MRI during anticipation and pain induced by esophageal distension at pain toleration level. ⋯ The pattern of brain activity suggests that, during anticipation, women may demonstrate stronger limbic inhibition, which is considered to be a cognitive modulation strategy for impending painful stimulation. During pain, women significantly activate brain areas associated with the affective and motivation components of pain. These responses may underlie the sex differences that exist in pain conditions, whereby women may attribute more emotional importance to painful stimuli compared with men.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Mar 2013
Antral recirculation in the stomach during gastric mixing.
We investigate flow in the stomach during gastric mixing using a numerical simulation with an anatomically realistic geometry and free-surface flow modeling. Because of momentum differences between greater and lesser curvatures during peristaltic contractions, time-averaged recirculation is generated in the antrum, with retropulsive flow away from the pylorus and compensation flow along the greater curvature toward the pylorus. Gastric content in the distal stomach is continuously transported to the distal antrum by the forward flow of antral recirculation, and it is then mixed by the backward retropulsive flow. ⋯ In the upright, prone, and right lateral positions, most of the antrum is filled with content, and the content is well mixed by antral recirculation. In contrast, in the supine and left lateral positions, most of the content is located outside antral recirculation, which results in poor mixing. The curved, twisted shape of the stomach substantially supports gastric mixing in fluid mechanical terms.
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Am. J. Physiol. Gastrointest. Liver Physiol. · Feb 2013
Clinical TrialPostprandial gut hormone responses and glucose metabolism in cholecystectomized patients.
Preclinical studies suggest that gallbladder emptying, via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells, may play a significant role in the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) and, hence, postprandial glucose homeostasis. We examined the secretion of gut hormones in cholecystectomized subjects to test the hypothesis that gallbladder emptying potentiates postprandial release of GLP-1. Ten cholecystectomized subjects and 10 healthy, age-, gender-, and body mass index-matched control subjects received a standardized fat-rich liquid meal (2,200 kJ). ⋯ The concentrations of GIP, GLP-2, and gastrin were similar in the two groups. In conclusion, cholecystectomized subjects had preserved postprandial GLP-1 responses in spite of decreased duodenal bile delivery, suggesting that gallbladder emptying is not a prerequisite for GLP-1 release. Cholecystectomized patients demonstrated a slight deterioration of postprandial glycemic control, probably because of metabolic changes unrelated to incretin secretion.