Effect of rectal distension on gallbladder emptying and circulating gut hormones

BACKGROUND: Abnormalities of upper gut motility, including a delay of gastric emptying and small bowel transit, found in patients with constipation may be secondary to factors originating in the colon or rectum as a result of faecal stasis. The aim was to determine if stimulation of mechanosensory function by rectal distension affects postprandial gallbladder emptying and release of gastrointestinal peptides participating in control of upper gut motility. MATERIALS AND METHODS: Eight healthy volunteers were studied with an electronic barostat and a plastic bag positioned in the rectum. Intrabag pressure was maintained at minimal distension pressure + 2 mmHg on one occasion and on a pressure that induced a sensation of urge on the other. Gallbladder volume and plasma concentrations of cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY (PYY) were measured before and after ingestion of a 450-kcal mixed liquid meal. RESULTS: Rectal distension enhanced maximum gallbladder emptying from 66 +/- 7% to 78 +/- 5% (P < 0.05). Distension tended to increase integrated plasma PYY from 77 +/- 30 pM min to 128 +/- 40 pM min in the first hour after the meal (P = 0.08) and it suppressed integrated plasma PP from 1133 +/- 248 pM min to 269 +/- 284 pM min in the second hour (P < 0.05). Integrated plasma CCK concentrations were not significantly affected. CONCLUSION: Mechanosensory stimulation of the rectum enhances postprandial gallbladder emptying and influences postprandial release of gut hormones involved in the regulation of gastrointestinal motility in healthy subjects. These mechanisms may play a role in the pathogenesis of the upper gastrointestinal motor abnormalities observed in constipated patients.     

Effect of meal and cimetidine on endogenous plasma gastrin, secretin and pancreatic polypeptide in experimental acid hypersecretion in dogs

In order to observe the plasma gastrin, secretin and pancreatic polypeptide (PP) levels in an acid hypersecretion state, the pyloric antrum was transposed onto the transverse colon in 4 mongrel dogs with a Heidenhain pouch. The effects of meal and cimetidine on these gut hormones and acid secretion levels were observed for 6 hr after meals. After antrocolic transposition (ACT), hypersecretion of acid and high plasma gastrin levels were observed both in the fasting and stimulated states. Plasma secretin levels were elevated for 6 postprandial hr, but were reduced by cimetidine as a result of marked suppression of acid secretion. Plasma PP levels also increased for 6 postprandial hr, but its responses were not altered with or without simultaneous administration of cimetidine. These findings indicate that acid hypersecretion in basal and postprandial states after ACT may be attributed to hypergastrinemia and that endogenous acid is capable of releasing secretion but not effective on the release of PP.     

Antroduodenal motility and small bowel transit during continuous intraduodenal or intragastric administration of enteral nutrition

BACKGROUND: Gastrointestinal intolerance is observed more frequently during intraduodenal (ID) tube feeding than during intragastric (IG) feeding, possibly because it evokes a stronger gastrointestinal response and accelerates small bowel transit. We have investigated whether the accelerated small bowel transit during ID feeding results from alterations in antroduodenal motility pattern. DESIGN: The effect of IG and ID infusion of a polymeric diet (Nutrison, 125 kcal h-1) on antroduodenal motility, small bowel transit time (SBTT) and gastrointestinal hormone release was studied in nine healthy subjects. These subjects were studied on three occasions for 6 h during fasting, continuous IG or ID feeding. RESULTS: Phase III recurrence time was significantly prolonged during IG feeding compared with fasting (240 +/- 51 vs. 136 +/- 24 min; P < 0.05). None of the subjects had recurrence of phase III during ID feeding; the fed motor pattern remained present. Parameters of fed motility (mean amplitude and motility index) were not significantly different between IG and ID feeding, although the frequency of antral and duodenal contractions was lower during ID than during IG feeding. SBTT was significantly accelerated during ID compared with IG feeding and with fasting (58 +/- 8 vs. 73 +/- 9 and 83 +/- 10 min respectively; P < 0.05). Plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) levels were significantly higher during ID than during IG feeding. Peptide YY (PYY) levels were significantly higher during ID than during fasting, but not during IG feeding CONCLUSIONS: During intraduodenal feeding, a fed motility pattern is preserved, whereas during intragastric feeding transition from a fed to a fasting motor pattern is observed in over 50% of the subjects. These differences may be related to augmented hormone release during intraduodenal feeding.     

Role of gut hormones in irritable bowel syndrome]

In irritable bowel syndrome (IBS), motility disturbances occur from the upper gastrointestinal tract to the distal colon, where regulatory peptides have a wide-spread distribution. Studies on basal and postprandial plasma levels of different gut hormones show that VIP, CCK, and motilin may be closely related to the symptoms including abdominal pain, diarrhea and constipation. In addition, peptide YY and NPY have effects on absorption in the intestine, and some opioid peptides exert actions on colonic motility in IBS patients. Recent studies revealed that gall bladder in IBS has an abnormal sensitivity to CCK-8, indicating that IBS patients has an generalized abnormality of the smooth muscle of the digestive tract. Gut hormones, which act as hormones, neurotransmitters and neuromodulators depending on their releasing site, may therefore play an important role in IBS patients.     

Delayed postprandial plasma bile acid response in coeliac patients with slow mouth-caecum transit

Coeliac patients are known to have an expanded bile salt pool which recirculates slowly due, at least in part, to impaired gall bladder contractility. We have investigated the possibility that delayed small bowel transit of chyme and bile may also contribute to this sluggish recycling. Plasma cholylglycine, total bile acids and cholecystokinin concentrations were measured after a lactulose-labelled test meal whose mouth-caecum transit time (M-C TT) was assessed by the breath hydrogen technique. Overall there were no significant differences in plasma bile acid profiles between seven healthy controls and a group of 25 coeliac patients. However, when subjects were divided according to their M-C TT, the 10 with the slowest transit were found to have significant elevation of fasting levels when compared with the 10 with the fastest transit, fasting total bile acids being 3.4 +/- 1.3 versus 0.7 +/- 0.6 mumol/l (P less than 0.02) and fasting cholylglycine being 0.43 +/- 0.17 versus 0.06 +/- 0.04 mumol/l (P less than 0.05) respectively. Peak bile acid levels did not differ significantly between subjects with fast or slow transit. However, subjects with slow transit were found to have a delay in the return of plasma bile acid levels to fasting levels so that the 4 h postprandial levels were significantly elevated when compared with those observed in the subjects with fast transit (total bile acids 3.6 +/- 1.2 versus 0.19 +/- 0.1 mumol/l and cholylglycine 0.70 +/- 0.13 versus 0.24 +/- 0.07 mumol/l respectively, both P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

慢传输型便秘大鼠结肠内Cajal间质细胞的变化

目的:研究慢传输型便秘(STC)大鼠结肠内Cajal间质细胞(ICC)的变化,探讨ICC在STC发病机制中的作用。方法:用复方苯乙哌啶灌胃法建立STC大鼠模型,免疫组化法检测大鼠结肠ICC,分析大鼠结肠不同部位ICC的变化。结果:STC组大鼠结肠ICC比对照组明显减少。结论:STC大鼠结肠内ICC明显减少,提示ICC在STC的发病机制中可能起重要作用。     

Gut hormones: Implications for the treatment of obesity

Bariatric surgery is the only effective treatment for patients with morbid obesity. This is no solution to the present obesity pandemic however. Currently licensed non-surgical pharmaceuticals are of limited efficacy and alternatives are needed.Harnessing the body's own appetite-regulating signals is a desirable pharmacological strategy. The gastrointestinal tract has a prime role in sensing and signalling food intake to the brain. Gut hormones are key mediators of this information, including: peptide YY (PYY), pancreatic polypeptide (PP), glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), ghrelin, amylin and cholecystokinin (CCK).This review summarises the latest knowledge regarding the physiological and pathophysiological role of gut hormones in regulating our food intake and how this knowledge could guide, or has guided, the development of weight-loss drugs. Up-to-date outcomes of clinical trials are evaluated and directions for the future suggested.     

Effect of somatostatin on postprandial gallbladder relaxation

Although the inhibitory effect of somatostatin (SST) on gallbladder contraction is well known, the influence of SST on gallbladder motility during the late postprandial or relaxation phase has not been studied. We therefore investigated the effect of SST on gallbladder relaxation and gut hormone release during the late postprandial phase. Eight healthy volunteers participated in two experiments performed in random order during continuous infusion of either SST or saline (placebo) starting 2 h after meal ingestion. At regular intervals, gallbladder volumes were measured (ultrasonography) and blood samples were taken for determination of plasma cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY) and neurotensin levels (radioimmunoassay). Postprandial gallbladder contraction was similar in both experiments: 68 ± 4% vs. 66 ± 4%. During SST infusion, postprandial gallbladder contraction was significantly (P<0·01) reduced (2874 ± 813% *240 min) compared with saline (9391 ± 1595% *240 min). Plasma CCK, PP, PYY and neurotensin levels were in the same range in the early postprandial phase but were significantly reduced during SST infusion compared with placebo (late postprandial phase). Plasma levels of CCK correlated with gallbladder volumes during both the contraction and relaxation phase (r=0·68, P=0·01 and r=0·61, P=0·008, respectively). SST enhances gallbladder relaxation and reduces hormone secretion in the late postprandial phase. The results point to an association between CCK and gallbladder volume not only during the postprandial contraction phase but also during the relaxation phase.     

Meal-stimulated cholecystokinin release and exocrine pancreatic secretion in dogs

To confirm the role of cholecystokinin (CCK) and secretin in digestion, exocrine pancreatic secretion, plasma CCK, and secretin were measured simultaneously in six dogs prepared with gastric and pancreatic fistulas after feeding a solid meal. Plasma CCK concentration determined by radioimmunoassay increased significantly from the basal level, reached a peak 35 min after meal ingestion, and after a dip it further increased toward the end of the 3-h observation. Pancreatic protein output increased significantly, peaked at the fifth 10-min period, and then declined progressively. Plasma CCK concentration and pancreatic protein output correlated significantly during the first postprandial hour. Plasma secretion demonstrated significant elevation at 15 min and a peak at 25 min after a meal. Plasma secretin correlated significantly with both bicarbonate output and flow rate during the 3 h. Simultaneous measurements of plasma CCK and secretin and of pancreatic secretion suggested that postprandial pancreatic secretion is primarily mediated by releases of CCK and secretin, but these hormones do not seem to be the only factors responsible for the secretion.     

Hormone-based therapies in the regulation of fuel metabolism and body weight

Background: The integrated central actions of hormones secreted from pancreatic islets, the gut and adipocytes regulate both energy homeostasis and body weight. Dysregulation in these neurohormonal pathways probably contributes to pathogenesis of obesity and type 2 diabetes. Objective: To examine hormone-based therapies targeting these interrelated pathways as potential treatments for obesity and diabetes. Methods: Preclinical and clinical data on therapies based on hormones secreted from the pancreas (glucagon, insulin, amylin and pancreatic polypeptide), gut (glucagon-like peptide-1, glucose dependent insulinotropic polypeptide, cholecystokinin and peptide YY) and adipose tissue (leptin and adiponectin) as potential treatments for diabetes and obesity are reviewed. Results/conclusions: In diabetes, hormone-based treatments have translated into new clinical platforms including insulin analogs, the GLP-1-like peptide receptor agonist exenatide and amylinomimetic pramlintide, which due to their complex interplay and the progressive nature of diabetes, can be utilized in different settings. Various peptide hormones and agonists/antagonists are currently under investigation as new approaches to treatment of obesity and diabetes.     

Can plasma human pancreatic polypeptide be used to detect diseases of the exocrine pancreas?

Plasma concentrations of human pancreatic polypeptide (HPP) parallel exocrine pancreatic secretion in response to stimulation with cholecystokinin. We determined prospectively the relationships among fasting HPP level, integrated HPP response to infusion of cholecystokinin, and output of trypsin and also the sensitivity, specificity, and predictive values of the fasting HPP level in the diagnosis of exocrine pancreatic disease. Our study group consisted of 19 patients with acute pancreatitis, 17 with chronic pancreatitis, and 25 with ductal adenocarcinoma of the pancreas and 27 control subjects. In the control patients and those with chronic pancreatitis, significant correlations were detected between HPP level and output of trypsin (P less than 0.001) in response to infusion of cholecystokinin and between fasting HPP and integrated HPP levels (P less than 0.004); no correlation was detected between HPP level and steatorrhea. The sensitivity, specificity, and negative and positive predictive values of the fasting HPP level for detection of either chronic pancreatitis or pancreatic cancer were similar and approximated 0.88, 0.67, 0.88, and 0.66, respectively. The HPP concentration had no value in detecting acute pancreatitis. Because the fasting HPP level has a high degree of negative predictability and is simpler to measure than the integrated HPP level or the output of trypsin, it may be a useful test in patients suspected of having either chronic pancreatitis or pancreatic cancer. A fasting HPP level of 125 pg/ml or greater could be used to exclude chronic pancreatitis or pancreatic cancer, but the finding of a value of less than 125 pg/ml necessitates use of other diagnostic tests for reliable determination of the presence of these diseases.     

Postprandial exocrine pancreatic function during long-term treatment with the somatostatin analogue SMS 201–995 in acromegalic patients

Long-term treatment with the somatostatin analogue SMS 201-995 (SMS) might impair exocrine pancreatic function, secretion of cholecystokinin (CCK) and pancreatic polypeptide (PP), and pancreatic size. In five acromegalics on chronic treatment with SMS, we investigated postprandial 6-h urinary excretion of p-aminobenzoic acid (PABA) and p-aminosalicylic acid (PAS) after s.c. injection of 100 micrograms SMS or placebo and after ingestion of 2 mmol nBT-PABA and 2 mmol PAS. In the acromegalics, urinary PABA/PAS ratio (reflecting exocrine pancreatic function) after SMS was similar to that after placebo (P greater than 0.10) and higher than in healthy volunteers (n = 8, P = 0.05). The initial inhibition of plasma CCK secretion by SMS was cancelled during the 3rd h after the meal, whereas PP release remained completely abolished. Pancreatic size as measured by ultrasonography, was not reduced in seven acromegalics compared with 14 healthy volunteers. It is concluded that despite a blunted release of the trophic hormone CCK, long-term treatment with SMS 201-995 neither induces an abnormally small pancreas nor deterioration of postprandial exocrine pancreatic function in patients with acromegaly.     

慢传输型便秘中医证型与心理因素的关系

目的:探讨慢传输型便秘(STC)的中医证型与心理因素的关系。方法:将95例STC患者进行中医辨证分型和神经症状评分,探讨中医证型与神经症状评分的关系。结果:肝郁气滞证神经症评分显著高于气虚肠燥证、气阴两虚证、脾肾阳虚证,差异显著(P<0.01)。结论:慢传输型便秘中医证型与心理因素之间存在明显关系,其中肝气郁滞与之关系最为密切。     

Bench-to-bedside review: The gut as an endocrine organ in the critically ill

In health, hormones secreted from the gastrointestinal tract have an important role in regulating gastrointestinal motility, glucose metabolism and immune function. Recent studies in the critically ill have established that the secretion of a number of these hormones is abnormal, which probably contributes to disordered gastrointestinal and metabolic function. Furthermore, manipulation of endogenous secretion, physiological replacement and supra-physiological treatment (pharmacological dosing) of these hormones are likely to be novel therapeutic targets in this group. Fasting ghrelin concentrations are reduced in the early phase of critical illness, and exogenous ghrelin is a potential therapy that could be used to accelerate gastric emptying and/or stimulate appetite. Motilin agonists, such as erythromycin, are effective gastrokinetic drugs in the critically ill. Cholecystokinin and peptide YY concentrations are elevated in both the fasting and postprandial states, and are likely to contribute to slow gastric emptying. Accordingly, there is a rationale for the therapeutic use of their antagonists. So-called incretin therapies (glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide) warrant evaluation in the management of hyperglycaemia in the critically ill. Exogenous glucagon-like peptide-2 (or its analogues) may be a potential therapy because of its intestinotropic properties.     

腹腔镜辅助结肠次全切除术治疗结肠慢传输性便秘48例临床效果研究

目的探讨腹腔镜辅助结肠次全切除术治疗结肠慢传输性便秘的临床效果。方法选择2009年1月～2012年3月在我院行结肠次全切除术的48例结肠慢传输性便秘患者,根据其手术方式将其分为腹腔镜组(25例)与开腹组(23例)。比较两组患者术中、术后情况及便秘症状改善率。结果腹腔镜组患者平均手术时间与开腹组相比,无统计学差异(P>0.05),但术中出血量明显少于开腹组,差异有统计学意义(P<0.05)。腹腔镜组患者肠道功能恢复时间及排便次数与开腹组相比,无统计学差异(P>0.05),而住院时间、术后引流管引流量、止痛剂使用次数、伤口并发症发生率显著低于开腹组,差异有统计学意义(P<0.05)。两组患者术后3、6个月便秘症状改善率无统计学差异(P>0.05)。结论腹腔镜辅助结肠次全切除术治疗结肠慢传输型便秘与传统开腹手术相比,治疗安全性高、并发症少、临床治疗效果良好,对缩短患者住院时间,促进其康复具有重要的临床意义。     

Effects of a Protein Preload on Gastric Emptying, Glycemia, and Gut Hormones After a Carbohydrate Meal in Diet-Controlled Type 2 Diabetes

OBJECTIVE

We evaluated whether a whey preload could slow gastric emptying, stimulate incretin hormones, and attenuate postprandial glycemia in type 2 diabetes.

RESEARCH DESIGN AND METHODS

Eight type 2 diabetic patients ingested 350 ml beef soup 30 min before a potato meal; 55 g whey was added to either the soup (whey preload) or potato (whey in meal) or no whey was given.

RESULTS

Gastric emptying was slowest after the whey preload (P < 0.0005). The incremental area under the blood glucose curve was less after the whey preload and whey in meal than after no whey (P < 0.005). Plasma glucose-dependent insulinotropic polypeptide, insulin, and cholecystokinin concentrations were higher on both whey days than after no whey, whereas glucagon-like peptide 1 was greatest after the whey preload (P < 0.05).

CONCLUSIONS

Whey protein consumed before a carbohydrate meal can stimulate insulin and incretin hormone secretion and slow gastric emptying, leading to marked reduction in postprandial glycemia in type 2 diabetes.The rate of gastric emptying and the incretin, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), response to a meal are known to be major determinants of postprandial blood glucose excursions (1,2). One strategy to minimize postprandial glycemia could be to administer a small load of protein or fat before a meal, so that the presence of nutrients in the small intestine induces the release of peptides such as GLP-1, GIP, and cholecystokinin (CCK) to slow gastric emptying and stimulate insulin secretion in advance of the main nutrient load (3,4). We hypothesized that a protein preload would reduce the postprandial glycemic excursion in type 2 diabetic patients by these mechanisms.     

肠易激综合征与胃肠激素的关系

目的　探讨胃肠激素在肠易激综合征 (IBS)患者血浆及乙状结肠粘膜中含量的变化及临床意义。方法　采用放射免疫法测定正常对照组及IBS患者血浆和乙状结肠粘膜胃动素 (MTL)、血管活性肠肽(VIP)、生长抑素 (SS)、胆囊收缩素 (CCK)的含量。结果　IBS腹泻型患者血浆及乙状结肠粘膜中MTL含量显著高于正常组及IBS便秘型组 (P <0 .0 1) ;便秘型组IBS患者乙状结肠粘膜VIP的含量高于正常组及腹泻型组IBS(P <0 .0 5 ) ,而各组间血浆中VIP无明显差异 (P >0 .0 5 ) ;血浆及乙状结肠粘膜SS的含量在便秘型组IBS中显著高于正常组及腹泻型组 (P <0 .0 1～ 0 .0 5 ) ;血浆CCK在腹泻组也明显高于正常组及便秘型组 (P <0 .0 1) ,在乙状结肠粘膜中各组间无明显不同 (P >0 .0 5 )。结论　四种胃肠激素可能在IBS的发病过程中起一定作用。     

Cholecystokinin receptor antagonist loxiglumide modulates plasma levels of gastro-entero-pancreatic hormones in man Feedback control of cholecystokinin and gastrin secretion

The effect of the potent specific cholecystokinin (CCK) receptor antagonist loxiglumide on meal-stimulated plasma concentrations of CCK, gastrin, pancreatic polypeptide (PP), neurotensin, glucose-dependent insulinotropic polypeptide (GIP), insulin and C peptide was investigated in a placebo-controlled study in 10 healthy male volunteers. Intravenous infusion of loxiglumide (10 mg kg-1 h-1) significantly augmented integrated incremental IR-CCK levels 7.3-fold after stimulation by a standard breakfast (504 +/- 54 vs 3.665 +/- 365 pmol-1 135 min-1, P less than 0.001), as measured by a specific CCK radioimmunoassay. Basal IR-CCK concentrations were not affected by administration of loxiglumide. Oral treatment with bile acids (2 g ursodeoxycholic acid plus 2 g chenodeoxycholic acid) together with the meal abolished this augmentation, whereas high-dose substitution with pancreatic enzymes (4.2 g pancreatin) reduced elevated IR-CCK levels by only 38%. CCK-like bioactivity, determined by a bioassay using rat pancreatic acini, was not detectable in all samples that contained loxiglumide at plasma concentrations of 100-250 micrograms ml-1. Plasma gastrin concentrations in response to the breakfast were elevated 3.2-fold during loxiglumide infusion and not influenced by substitution with bile acids or pancreatic enzymes. Meal-stimulated integrated incremental plasma PP concentrations were significantly suppressed (55-65% inhibition, P less than 0.01) by loxiglumide. Infusion of the CCK receptor antagonist only slightly increased postprandial peak plasma glucose, insulin and C-peptide levels, whereas GIP and neurotensin levels were not significantly influenced. These findings suggest: (i) CCK secretion is under feedback control by intraduodenal bile acids and to a lesser extent by pancreatic enzymes; (ii) simultaneous extraction of CCK and loxiglumide results in circulating plasma CCK-like bioactivity of zero; (iii) gastrin secretion is feedback controlled via an indirect mechanism probably involving CCK-induced somatostatin secretion; (iv) release of PP is under inhibitory control of CCK; (v) CCK does not play a major role as insulinotropic hormone in the entero-insular axis in humans.     

Radioimmunoassay of gastric inhibitory polypeptide

A radioimmunoassay for the measurement of gastric inhibitory polypeptide (GIP) in unextracted plasma in man has been developed using a rabbit antiserum raised against porcine GIP. Porcine GIP was employed also as standard and to produce a 125I-labelled tracer. The assay was able to distinguish 110 pg/ml GIP from zero in plasma samples. Negligible cross-reactivity was demonstrated with cholecystokinin, insulin, pancreatic polypeptide, glucagon, secretin, and vasoactive intestinal polypeptide. The mean overnight fasting plasma GIP level in 28 normal subjects was 203 pg/ml (range: undetectable--420 pg/ml). Plasma GIP levels rose, within 45 minutes of eating a mixed meal, to a mean level of 1573 pg/ml.