Effects of alpha-glucosidase inhibitors on mouth to caecum transit time in humans.

The alpha-glucosidase inhibitors acarbose and miglitol have been successfully used to control postprandial hyperglycaemia in diabetics. They probably work by slowing carbohydrate digestion and absorption, but their effect on mouth to caecum transit time has not been studied. The effect acarbose (100 mg), miglitol (100 mg), and placebo on mouth to caecum transit time (380 kcal breakfast with 20 g of lactulose) was investigated in 18 normal volunteers using breath hydrogen analysis. Both miglitol and acarbose significantly increased breath hydrogen excretion (F2,34 = 6.31, p = 0.005) and shortened the mouth to caecum transit time (F2,34 = 3.49, p = 0.04) after breakfast compared with placebo. There was a significant negative correlation between breath hydrogen excretion and mouth to caecum transit time suggesting that with shorter transit times significantly more carbohydrates were spilled into the colon. These results indicate that alpha-glucosidase inhibitors accelerate mouth to caecum transit time by inducing carbohydrate malabsorption.     

Measurement of gastric emptying, intestinal transit time and colonic filling by scintiscan in healthy subjects

A scintigraphic technique allowing combined measurements of gastric emptying, small intestinal transit time and colonic filling was developed and its reproducibility assessed in 8 healthy volunteers. Each subject underwent four tests: a) two were performed in the fasting state (99mTc labelled water, added to lactulose), b) two in the postprandial state (balanced meal, 1,750 kJ, included pellets labelled with 111In, the gut transit of which being nearly the same as dietary fibers). Intestinal transit was modeled using linear operators (expressed as a convolution product). In fasting state (lactulose), orocecal transit time of water was 109 +/- 60 min and 89 +/- 36 min (m +/- DS) for the first and second tests, respectively. In the postprandial state, values were 297 +/- 37 min and 293 +/- 43 min respectively for the pellets. Small bowel transit times were 135 +/- 70 and 103 +/- 40 min respectively in fasting state for water, and 209 +/- 47 and 209 +/- 29 min respectively in postprandial state for the pellets. Determination of residual variance showed that reproducibility of the test was better in the postprandial state than in the fasting state. Water orocecal transit times measured using this technique and lactulose orocecal transit time measured using hydrogen breath test were strongly correlated (r = 0.98, n = 12, P less than 0.01). This isotopic method provides a reproducible assessment of gastric emptying, small bowel transit, and colonic filling and could represent a reliable and non invasive tool for further physiological and pharmacological studies.     

Plasma peptide YY (PYY) in dumping syndrome

The newly isolated hormonal peptide PYY is mainly localized to endocrine cells of the lower intestinal mucosa. The release of PYY by oral glucose was studied in six patients with the dumping syndrome to ascertain the effect of this condition on PYY release. Plasma PYY concentrations were greatly increased following oral glucose in patients with the dumping syndrome compared with healthy controls. In a separate series of experiments, the effect of somatostatin infusion on the PYY release by glucose in these patients was investigated. The release of PYY was completely blocked by infusion of somatostatin, and its release from the bowel in normal subjects may therefore be modulated by local somatostatin in the gut. PYY has been shown to inhibit gastric acid secretion and emptying, at plasma concentrations similar to those seen after glucose, in patients with the dumping syndrome. PYY may therefore be a factor involved in the pathophysiological changes associated with this condition.Gastrointestinal Laboratory, St. Thomas Hospital, London SE1 7EH, U.K.     

Effects of progesterone on gastric emptying and intestinal transit in male rats

AIM: To study the dose-dependent of progesterone (P) effect and the interaction between the oxytocin (OT) and P on gastrointestinal motility. METHODS: In order to monitor the gastric emptying and intestinal transit, the SD male rats were intubated via a catheter with normal saline (3 ml/kg) containing Na(2)(51)CrO(4) (0.5 microCi/ml) and 10% charcoal. OT was dissolved into normal saline and P was dissolved into 75% alcohol. RESULTS: Low does of P (1 mg/kg, i.p.) enhanced the gastric emptying (75+/-3%, P<0.05) and high dose of P (5 mg/kg, i.p.) inhibit it (42+/-11.2%, P<0.01). P (1 mg/kg) increased the intestinal transit (4.2+/-0.3, P<0.05) while the higher dose (10-20 mg/kg) had no effect. OT (0.8 mg/kg, i.p.) inhibited the gastric emptying (23.5+/-9.8%, P<0.01). The inhibitory effects of P(20 mg/kg) (32+/-9.7%, P<0.05) and OT (0.8 mg/kg) on gastric emptying enhanced each other when the two chemicals were administrated simultaneously (17+/-9.4%, P<0.01). CONCLUSION: Low dose of P increased GI motility while high dose of P decreased it. During the later period of pregnancy, elevated plasma level of OT may also participate in the gastrointestinal inhibition.     

Effects of progesterone on gastric emptying and intestinal transit in male rats

AIM: To study the dose-dependent of progesterone (P) effect and the interaction between the oxytocin (OT) and Pon gastrointestinal motility.METHODS: In order to monitor the gastric emptying andintestinal transit, the SD male rats were intubated via acatheter with normal saline (3 mi/kg) containing Na251 CrO4(0.5 μCi/ml) and 10 % charcoal.OT was dissolved intonormal saline and P was dissolved into 75 % alcohol.RESULTS: Low does of P (1 mg/kg, i. p. ) enhanced thegastric emptying (75 ± 3 %, P＜ 0.05) and high dose of P (5mg/kg, i.p. ) inhibit it (42± 11.2 %, P＜ 0.01). P (1 rog/kg)increased the intestinal transit (4.2 ± 0. 3, P ＜ 0.05) whilethe higher dose ( 10-20 mg/kg) had no effect. OT (0.8 mg/kg, i.p. ) inhibited the gastric emptying (23.5 ± 9.8 %, P ＜0.01). The inhibitory effects of P (20 mg/kg) (32± 9.7 %, P＜ 0.05) and OT (0.8 mg/kg) on gastric emptying enhancedeach other when the two chemicals were administratedsimultaneously ( 17 ± 9.4 %, P ＜ 0.01).CONCLUSION: Low dose of P increased Gl motility whilehigh dose of P decreased it. During the later period ofpregnancy, elevated plasma level of OT may also participatein the gastrointestinal inhibition.     

Localization of peptide YY (PYY) in gastrointestinal endocrine cells and effects on intestinal blood flow and motility.

In immunohistochemical studies using antisera to peptide YY (PYY), a 36 amino acid polypeptide isolated from porcine duodenum, it was found that PYY-like immunoreactivity occurred mainly in endocrine cells of the gastrointestinal mucosa. PYY-immunoreactive cells were particularly abundant in the distal intestine and have been observed in five species, including man. By radioimmunoassay it was found that, in the rat, the amount of PYY immunoreactivity was about 100-fold higher in the colon than in the duodenum. The chromatographic profiles of PYY immunoreactivity from the rat colon and porcine PYY on a SP-Sephadex ion exchanger were similar. Furthermore, serial dilutions of extracts from the rat colon and porcine PYY had parallel displacement curves in radioimmunoassay. Close intraarterial administration of PYY in cats caused an intestinal vasoconstriction and an inhibition of jejunal and colonic motility. Simultaneously there was a rise in systemic arterial blood pressure. These effects of PYY were also observed after pretreatment with adrenergic blocking agents. It is concluded that PYY is a gastrointestinal peptide that is present mainly in endocrine cells of distal intestine and that has effect on both intestinal motility and the cardiovascular system.     

Effect of tricyclamol on gastric emptying and intestinal transit

Summary The effects of a placebo, 50 mg. dose, and the O.E.D. of Tricyclamol on gastric emptying and intestinal transit of a standard barium mixture and Ewald meal were compared in nine patients with duodenal ulcer. Each patient served as his own control. The medicament was given half an hour prior to the ingestion of the barium mixture and Ewald meal. Serial x-rays of the abdomen were then taken.No significant differences were found in the rate of gastric emptying following the placebo or a 50 mg. dose of Tricyclamol. However, the O.E.D. of Tricyclamol produced a delay in gastric emptying of the barium and Ewald mixture at 1- and 2-hour intervals, but none at the 4-hour period. Thus, the O.E.D. of Tricyclamol, though a multiple of the 50 mg. dose, did not produce excessive delay in gastric emptying of the barium mixture and Ewald meal. However, some but no important delay in the progress of the barium along the intestine was noted after Tricyclamol as compared to that produced by the placebo.The authors wish to thank Dr. James B. Hammond of the Eli Lilly and Co., for the Generous supply of Tricyclamol methylsulfate.     

糖尿病病人胃排空及小肠运动时间变化的研究

目的　了解糖尿病病人液体和固体混合餐后胃排空及固体食物在小肠的运行情况。方法　采用双核素标记液体和固体后 ,用SPECT探头采集感兴趣区图像 ,计算胃排空和小肠运行时间指标。结果　糖尿病病人固体全胃半排空 近端胃半排空 远端胃最大计数时间均较正常人明显延迟 ,4 0 %～ 4 4 %病人超过正常范围 ,延迟相时间均数变化不明显 ,但 4 8%超出正常范围 ,液体排空各指标变化不明显。而小肠运行时间在糖尿病病人延迟明显。结论　糖尿病病人固体食物胃肠运行时间延迟 ,而液体胃排空无异常变化。     

Centrally administered neuropeptide Y (NPY) inhibits gastric emptying and intestinal transit in the rat

Neuropeptide Y is distributed abundantly not only in the brain, but also in the gastrointestinal tract and suppresses intestinal muscle contraction in isolated muscle preparations. The purpose of the present study was to determine whether centrally administered neuropeptide Y modulated gastric emptying and intestinal transit in conscious rats. Graded doses of neuropeptide Y were administered intracisternally 1 min before ingestion of test meals through an oral tube. Four hours after ingestion of 60 Amberlite pellets, the rats were sacrificed and residual pellets in the stomach and the small intestine segments were counted to calculate the solid meal transit rate. The liquid meal transit rate was calculated 1 hr after 0.07% phenol red ingestion by determining the residual phenol red in the stomach and the small intestine segments. Neuropeptide Y elicited potent suppression of gastric emptying and intestinal transit of both solid and liquid meals. Pretreatment with propranolol antagonized, whereas phentolamine did not affect, the suppressive effect of central neuropeptide Y. Although carbachol blocked the effects of neuropeptide Y, neither atropine nor hexamethonium altered the actions of neuropeptide Y. In conclusions, centrally administered neuropeptide Y strongly inhibited gastrointestinal transit by stimulating a beta-adrenergic pathway.     

Effect of enprostil on gastric emptying, intestinal transit time and post-prandial release of gastro-intestinal peptides

The effect of an oral dose of 70 micrograms enprostil (a prostaglandin E2 analogue) on the post-prandial hormone response to a test breakfast was examined in a double-blind, placebo-controlled, cross-over study in 10 healthy volunteers. Enprostil markedly reduced the post-prandial rises in insulin and glucose-dependent insulinotropic peptide (GIP) but plasma glucose remained unchanged. To study the effects on gut motility 8 healthy volunteers ingested a liquid meal containing 75 g glucose, 20 g lactulose and 99mTc colloid after taking placebo or 70 micrograms enprostil. Gastric emptying, measured using a gamma camera, was unchanged but mouth-to-caecum transit time was significantly longer on enprostil; time to half maximal breath hydrogen: placebo 119 min, enprostil 200 min (p less than 0.05). This delay was associated with a reduced and delayed post-prandial rise in GIP and insulin and with other changes in the gut hormone profile.     

Effect of cisapride on gastric emptying and ileal transit time of balanced liquid meal in healthy subjects

Cisapride is a new prokinetic gastrointestinal agent which has been shown to be able to increase gastric emptying and intestinal transit time in experimental animals and in patients with preexisting motility alterations. Up to now, however, clinical research evaluating the activity of the drug in healthy subjects is very limited. We have therefore undertaken a placebo-controlled study to simultaneously investigate the effect of cisapride (20 mg p.o.) on gastric emptying and intestinal transit time of a balanced liquid meal in 9 healthy volunteers. Median gastric half-time was 60 min after cisapride, as compared to 73 min after placebo (p less than 0.05). Intestinal transit time was similar after cisapride (75 min) or after placebo (105 min). These data confirm that cisapride significantly increases the speed of gastric emptying also in normal subjects. The lack of effect on intestinal transit could be explained by the interindividual variation observed in our experiments.     

NIA0003The role of peptide YY (PYY) in the control of appetite

Peptide YY (PYY) is a 36 amino acid gut hormone produced by the distal intestinal tract that binds the Y2 receptor in the hypothalamic arcuate nucleus. We showed that increasing calorie load in normal weight humans and rodents causes a graded rise in endogenous PYY ( P <  0.05). Graded doses of exogenous PYY showed a dose response curve for increased satiety ( P  < 0.05) and reduced calorie intake ( P <  0.05). This study demonstrated two threshold levels, the lower marking the start of appetite reduction ( P =  0.04) and the upper the onset of nausea ( P =  0.03). We subsequently showed that obese humans and rodents have lower postprandial PYY responses ( P <  0.05). Reduced plasma PYY was characterized by normal PYY mRNA levels and higher tissue PYY levels, indicating normal production, but attenuated release from the distal gut. However in obese humans and rodent exogenous PYY was still effective at increasing satiety and reducing food intake ( P <  0.05). Rodents following gastric bypass showed elevated PYY, reduced food intake and gut hypertrophy ( P =  0.01), while blockade of endogenous PYY increased food intake ( P =  0.04). In man, gastric bypass, but not gastric banding caused increased postprandial PYY favouring enhanced satiety ( P =  0.001). Our prospective human gastric bypass study showed progressively increasing PYY responses associated with enhanced satiety ( P <  0.05). The sustained nature of appetite reduction after gastric bypass may partly be explained by gut adaptation and chronic elevation of PYY. Thus obesity is associated with low PYY release that reduces satiety and reinforces obesity. The maladaptive reduction in PYY release can however be overcome by gastric bypass.     

Effects of loxiglumide on gallbladder emptying in healthy volunteers

This study evaluates the effects of the specific cholecystokinin receptor antagonist loxiglumide on gall-bladder emptying after a meal or after intravenous infusion of caerulein in humans. Ten healthy male volunteers were studied five times on separate days. The following five studies were performed in randomized order: (a) caerulein was intravenously infused at doses increasing from 7.5 to 120 ng/kg.h without the antagonist; (b) in addition to increasing doses of caerulein, loxiglumide was given intravenously at doses of 0.2, 1.0, or 5.0 mg/kg.h; (c) a solid-liquid 800-kcal meal was given without loxiglumide; (d) the 800-kcal meal was given with simultaneous infusion of 1 or 5 mg/kg.h loxiglumide; and (e) loxiglumide (5 mg/kg.h) was given. without caerulein or the test meal. Gallbladder volume was measured by ultrasound. Loxiglumide dose-dependently inhibited gallbladder emptying induced by caerulein or the meal. High doses of the antagonist did not only abolish meal-induced gallbladder emptying but increased gallbladder volume after administration of caerulein or the meal when compared with prior fasting values. The antagonist given alone markedly increased gallbladder volumes compared with prior fasting values. In conclusion, given alone markedly increased gallbladder volumes compared with prior fasting values. In conclusion, cholecystokinin is the hormone primarily and mainly responsible for mediation of gallbladder emptying after a regular meal. Cholecystokinin might also play a physiologic role in the regulation of the fasting tone of the gallbladder.     

A study on PP family peptide receptor: I. The distribution of peptide YY (PYY) receptor in the brain

Peptide YY (PYY) was discovered in the porcine gut by Tatemoto in 1982. PYY has recently been found in the central nervous system. This has provoked studies of PYY effects when centrally administrated. We investigated the specific binding of radioactive PYY (125I-PYY) to brain membranes in pigs and dogs. PYY chiefly bound to the hippocampus, as well as to the pituitary gland, hypothalamus, and amygdala, suggesting that PYY acts on the limbic-hypothalamic-pituitary axis. PYY binding in the brain had a high-affinity and a low-affinity component (dissociation constant, 1.39 X 10(-10) M and 3.72 X 10(-8) M, respectively). The binding sites were highly specific for PYY and neuropeptide Y (NPY), but not for pancreatic polypeptide (PP) or other peptide hormones such as cholecystokinin octapeptide, methionine enkephalin, adrenocorticotropic hormone, and thyrotropic releasing hormone. The similar affinities for PYY and NPY imply that these peptides regulate brain functions through interaction with common receptor site(s).     

Influence of acid suppressants on gastric emptying: cross-over analysis in healthy volunteers

BACKGROUND: Gastric emptying plays an important role in gastroesophageal reflux disease. Acid suppressants such as H2 receptor antagonists and/or proton pump inhibitors are often used in patients with gastroesophageal reflux disease. However, it remains controversial whether H2 receptor antagonists and proton pump inhibitors delay or accelerate gastric emptying. Here, the influence of acid suppressants on gastric emptying was evaluated via a cross-over study using the [13C]-labeled acetate breath test. METHODS: Twenty normal male subjects without gastroesophageal reflux disease symptoms were enrolled. Gastric emptying was investigated five times in every subject by the [13C]-labeled acetate breath test with oral administration of the vehicle, domperidone, and three acid suppressants: ranitidine, famotidine and rabeprazole. Gastric emptying was estimated by the values of T(max-calc), T(1/2) and %dose/2 h calculated from the 13CO2 breath excretion curve. RESULTS: Using the T(max-calc) values, rabeprazole, ranitidine and famotidine did not influence gastric emptying time in comparison with vehicle administration. Using the T(1/2) and %dose/2 h values, rabeprazole tended to delay gastric emptying. Domperidone produced a statistically significant acceleration of gastric emptying for all three variables (P < 0.05). CONCLUSION: Oral dosage of the H2 receptor antagonists, ranitidine and famotidine, has no significant effect on gastric emptying. However, rabeprazole may delay gastric emptying more strongly than H2 receptor antagonists.