Synchronized gastric electrical stimulation improves delayed gastric emptying in nonobese mice with diabetic gastroparesis.

The aim of this study was to investigate the effect and mechanism of synchronized gastric electrical stimulation (SGES) on gastric emptying in nonobese mice with diabetic gastroparesis (DB-GP). Eight control mice and 48 nonobese diabetic (NOD) mice with two pairs of gastric electrodes were used in this study. The study included seven groups in a randomized order [control, diabetes (DB), DB-GP, DB + SGES, DB-GP + SGES, DB-GP + Atropine, and DB-GP + SGES + Atropine groups]. In the control, DB, DB-GP, and DB-GP + Atropine groups, gastric emptying was measured in BLAB/cJ mice (control group) or NOD mice with a duration of diabetes of 0-7 days (DB group) or 28-35 days (DB-GP or DB-GP + Atropine group). In the DB + SGES, DB-GP + SGES, and DB-GP + SGES + Atropine groups, the experiment was the same as the corresponding DB, DB-GP, and DB-GP + Atropine groups except that SGES was applied during the experiment. SGES was applied via the proximal pair of electrodes and synchronized with the intrinsic gastric slow waves. The following results were obtained: 1) gastric emptying was delayed in NOD mice with a duration of diabetes of 28-35 days; 2) SGES was able to significantly increase gastric emptying in both diabetic mice and diabetic gastroparetic mice; and 3) the excitatory effect of SGES was completely blocked by atropine. SGES accelerates gastric emptying in NOD mice with diabetic gastroparesis. The effect of SGES on gastric emptying is mediated via the cholinergic pathway. These findings suggest that SGES may have a therapeutic potential for treating patients with diabetic gastroparesis.     

Inhibitory effects and mechanisms of intestinal electrical stimulation on gastric tone, antral contractions, pyloric tone, and gastric emptying in dogs

The aim of this study was to investigate the effects and mechanisms of intestinal electrical stimulation (IES) on gastric tone, antral and pyloric contractions, and gastric emptying in dogs. Female hound dogs were equipped with a duodenal or gastric cannula, and one pair of serosal electrodes was implanted in the small intestine. The study consisted of five different experiments. Liquid gastric emptying was assessed by collection of chyme from the duodenal cannula in a number of sessions with and without IES and with and without N-nitro-l-arginine (l-NNA). Postprandial antral and pyloric contractions were measured with and without IES and in the absence and presence of l-NNA or phentolamine by placement of a manometric catheter into the antrum and pylorus via the duodenal cannula. Gastric tone was assessed by measurement of gastric volume at a constant pressure. Gastric emptying was substantially and significantly delayed by IES or l-NNA compared with the control session. IES-induced delay of gastric emptying became normal with addition of l-NNA. IES reduced gastric tone, which was blocked by l-NNA. IES also inhibited antral contractions (frequency and amplitude), and this inhibitory effect was not blocked by l-NNA but was blocked by phentolamine. IES alone did not affect pyloric tone or resistance, but IES + l-NNA decreased pyloric tone. In conclusion, IES reduces gastric tone via the nitrergic pathway, inhibits antral contractions via the adrenergic pathway, does not affect pyloric tone, and delays liquid gastric emptying. IES-induced delay of gastric emptying is attributed to its inhibitory effects on gastric motility.     

Restraint stress augments postprandial gastric contractions but impairs antropyloric coordination in conscious rats

Central corticotropin-releasing factor (CRF) plays an important role in mediating restraint stress-induced delayed gastric emptying. However, it is unclear how restraint stress modulates gastric motility to delay gastric emptying. Inasmuch as solid gastric emptying is regulated via antropyloric coordination, we hypothesized that restraint stress impairs antropyloric coordination, resulting in delayed solid gastric emptying in conscious rats. Two strain gauge transducers were sutured onto the serosal surface of the antrum and pylorus, and postprandial gastric motility was monitored before, during, and after restraint stress. Antropyloric coordination, defined as a propagated single contraction from the antrum to the pylorus within 10 s, was followed by > or = 20 s of quiescence. Restraint stress enhanced postprandial gastric motility in the antrum and pylorus to 140 +/- 9% and 134 +/- 9% of basal, respectively (n = 6). The number of episodes of antropyloric coordination before restraint stress, 2.4 +/- 0.4/10 min, was significantly reduced to 0.6 +/- 0.3/10 min by restraint stress. Intracisternal injection of the CRF type 2 receptor antagonist astressin 2B (60 microg) or guanethidine partially restored restraint stress-induced impairment of antropyloric coordination (1.6 +/- 0.3/10 min, n = 6). The restraint stress-induced augmentation of antral and pyloric contractions was increased by astressin 2B and guanethidine but abolished by atropine, hexamethonium, and vagotomy. Restraint stress enhanced postprandial gastric motility via a vagal cholinergic pathway. Restraint stress-induced delay of solid gastric emptying is due to impairment of antropyloric coordination. Restraint stress-induced impairment of antropyloric coordination might be mediated via a central CRF pathway.     

Disturbed gastric motility and pancreatic hormone release in diabetes mellitus.

BACKGROUND AND AIMS: The influence of glucose metabolism and postprandial release of glucagon on gastric emptying in diabetes mellitus is still unclear. The aim of this study was to assess the relationship between glucose, insulin and glucagon and alterations of gastric motility in symptomatic diabetic subjects with delayed gastric emptying. METHODS: Scintigraphy for solids and liquids, 13C-acetate breath test, electrogastrography and antral manometry were assessed in 20 symptomatic subjects with diabetes mellitus type II and in 20 healthy controls. Simultaneously, serum glucose, glucagon and insulin levels were determined during the functional studies. RESULTS: Postprandial increase in antral motility and myoelectrical activity were seen in controls, but were missing in the group with diabetes mellitus. Moreover, in the fasting state the dominant frequency instability coefficient observed in healthy individuals and in subjects with diabetes of short (<5 years) duration was significantly reduced in subjects with longer duration of diabetes while the postprandial increase in dominant frequency instability coefficient was missing in all diabetics. Following the standard test meal, serum glucose and plasma glucagon in the diabetics increased to a significantly higher degree when compared to controls. CONCLUSIONS: Symptomatic subjects with delayed gastric emptying present abnormal patterns of gastric motor and electrical activity. Higher than normal postprandial plasma levels of glucagon may, at least in part, be responsible for disturbed gastric motility in non-insulin-dependent diabetic subjects.     

Peripheral mechanisms of sibutramine involving proximal gastric motility in dogs

Objective: Sibutramine, a serotonin‐norepinephrine uptake inhibitor, has been used for treating obesity. However, its possible mechanisms involving gastric motility have not been reported. The aim of this study was to evaluate the effects of sibutramine on gastric accommodation and antral motility. Research Methods and Procedures: The study was performed in seven dogs with a stomach cannula and composed of two separate experiments: antral contractions and gastric tone. Each experiment included two sessions on 2 separate days in a randomized order: a control session and a treatment session with sibutramine (5 mg/kg per os) administrated 2 hours before the study. Results: Sibutramine significantly increased fasting gastric tone; the gastric volume in the fasting state at baseline was 103.8 ± 12.3 mL and significantly decreased to 35.3 ± 16.0 mL with sibutramine (p = 0.0075). Sibutramine also impaired gastric accommodation. The average postprandial gastric volume was 472.1 ± 16.7 mL in the control session and reduced to 302.2 ± 53.6 mL with sibutramine (p = 0.013). The average postprandial increase in gastric volume during the 60‐minute postprandial period with sibutramine was significantly lower than the corresponding values in the control session: 266.8 ± 46.1 vs. 393.9 ± 15.3 mL (p = 0.03). Sibutramine had no effects on postprandial antral contractions. Discussion: Sibutramine increases gastric tone and impairs gastric accommodation to an orally ingested meal. The inhibitory effect of sibutramine on gastric accommodation may partially explain the reduced food intake with sibutramine in patients with obesity.     

Determination of gastric emptying in nonobese diabetic mice

Animal studies on diabetic gastroparesis are limited by inability to follow gastric emptying changes in the same mouse. The study aim was to validate a nonlethal gastric emptying method in nonobese diabetic (NOD) LtJ mice, a model of type 1 diabetes, and study sequential changes with age and early diabetic status. The reliability and responsiveness of a [(13)C]octanoic acid breath test in NOD LtJ mice was tested, and the test was used to measure solid gastric emptying in NOD LtJ mice and nonobese diabetes resistant (NOR) LtJ mice. The (13)C breath test produced results similar to postmortem recovery of a meal. Bethanechol accelerated gastric emptying [control: 92 +/- 9 min; bethanechol: 53 +/- 3 min, mean half emptying time (T(1/2)) +/- SE], and atropine slowed gastric emptying (control: 92 +/- 9 min; atropine: 184 +/- 31 min, mean T(1/2) +/- SE). Normal gastric emptying (T(1/2)) in nondiabetic NOD LtJ mice (8-12 wk) was 91 +/- 2 min. Aging had differing effects on gastric emptying in NOD LtJ and NOR LtJ mice. Onset of diabetes was accompanied by accelerated gastric emptying during weeks 1-2 of diabetes. Gastric emptying returned to normal by weeks 3-5 with no delay. The [(13)C]octanoic acid breath test accurately measures gastric emptying in NOD LtJ mice, is useful to study the time course of changes in gastric emptying in diabetic NOD LtJ mice, and is able to detect acceleration in gastric emptying early in diabetes. Opposing changes in gastric emptying between NOD LtJ and NOR LtJ mice suggest that NOR LtJ mice are not good controls for the study of gastric emptying in NOD LtJ mice.     

Effect of ghrelin on gastric myoelectric activity and gastric emptying in rats

Ghrelin is a recently discovered peptide in the endocrine cells of the stomach, which may stimulate gastric motility via the vagal nerve pathway. However, the mechanism of ghrelin-induced changes in gastrointestinal motility has not been clearly defined. The purpose of this study was to investigate the pharmacological effects of ghrelin on gastric myoelectrical activity and gastric emptying in rats, and to investigate whether cholinergic activity is involved in the effects of ghrelin. The study was performed on Sprague-Dawley rats implanted with serosal electrodes for electrogastrographic recording. Gastric slow waves were recorded from fasting rats at baseline and after injection of saline, ghrelin, atropine, or atropine+ghrelin. Gastric emptying of non-caloric liquid was measured by the spectrophotometric method in conscious rats. Intravenous administration of rat ghrelin (20 microg/kg) increased not only dominant frequency, dominant power and regularity of the gastric slow wave but also the gastric emptying rate when compared with the control rats (P<0.01, P<0.05, P<0.05, P<0.001 respectively). These stimulatory actions of ghrelin on both gastric myoelectrical activity and gastric emptying were not fully eliminated by pretreatment with atropine sulphate. These results taken together suggest that ghrelin may play a physiological role in the enteric neurotransmission controlling gastric contractions in rats.     

Pressure-geometry relationship in the antroduodenal region in humans

Understanding of the control mechanisms underlying gastric motor function is still limited. The aim of the present study was to evaluate antral pressure-geometry relationships during gastric emptying slowed by intraduodenal nutrient infusion and enhanced by erythromycin. In seven healthy subjects, antral contractile activity was assessed by combined dynamic magnetic resonance imaging and antroduodenal high-resolution manometry. After intragastric administration of a 20% glucose solution (750 ml), gastric motility and emptying were recorded during intraduodenal nutrient infusion alone and, subsequently, combined with intravenous erythromycin. Before erythromycin, contraction waves were antegrade (propagation speed: 2.7 +/- 1.7 mm/s; lumen occlusion: 47 +/- 14%). Eighty-two percent (51/62) of contraction waves were detected manometrically. Fifty-four percent of contractile events (254/473) were associated with a detectable pressure event. Pressure and the degree of lumen occlusion were only weakly correlated (r(2) = 0.02; P = 0.026). After erythromycin, episodes of strong antroduodenal contractions were observed. In conclusion, antral contractions alone do not reliably predict gastric emptying. Erythromycin induces strong antroduodenal contractions not necessarily associated with fast emptying. Finally, manometry reliably detects ~80% of contraction waves, but conclusions from manometry regarding actual contractile activity must be made with care.     

Excitatory effects of synchronized intestinal electrical stimulation on small intestinal motility in dogs

The aim of this study was to investigate effects of synchronized intestinal electrical stimulation (SIES) on small intestinal motility in dogs. Seventeen dogs were equipped with a duodenal cannula for the measurement of small bowel motility using manometry; an additional cannula was equipped in six of the dogs with 1.5 m distal to the first one for the measurement of small intestinal transit. Two pairs of bipolar electrodes were implanted on the small intestinal serosa with an interval of 5 cm; glucagon was used to induce postprandial intestinal hypomotility. Eleven dogs were used for the assessment of the small intestinal contractions in both fasting and fed states. The other six dogs were used for the measurement of small intestinal transit. We found that 1) SIES induced small intestinal contractions during phase I of the migrating motor complex (MMC) (contractile index or CI: 5.2 +/- 0.6 vs. 10.3 +/- 0.7, P = 0.003); 2) in the fed state, SIES significantly improved glucagon-induced small intestinal postprandial hypomotility (CI: 3.4 +/- 0.5 vs. 6.0 +/- 0.3, P = 0.03); 3) SIES significantly accelerated small intestinal transit delayed by glucagon (70.4 +/- 3.1 vs. 44.5 +/- 3.1 min, P < 0.01); 4) there was a negative correlation between the CI and transit time (r = -0.427, P = 0.048); and 5) the excitatory effect of SIES was blocked by atropine. SIES may have a therapeutic potential for treating patients with small intestinal disorders.     

Intracerebroventricular administration of MK-801 increases food intake through mechanisms independent of gastric emptying

Systemic or hindbrain administration of MK-801, a noncompetitive N-methyl-D-aspartate receptor antagonist, increases meal size. To examine whether MK-801 enhances intake by increasing gastric emptying, we administered MK-801 (2.0 microg/3.0 microl) into the fourth ventricle [intracerebroventricular (ICV)] and measured feeding and gastric emptying of 5-ml NaCl or 15% sucrose loads. In a parallel experiment, we examined food intake and gastric emptying following intraperitoneal (IP) injection of MK-801 (100 microg/kg). MK-801, either IP or ICV, increased 30-min sucrose intake compared with control (12.3 +/- 0.7 vs. 9.8 +/- 0.5 and 16.6 +/- 2.0 vs. 10.7 +/- 0.7 ml, for IP and ICV administration, respectively). Also, IP MK-801 increased 5-min gastric emptying of NaCl (4.13 +/- 0.1 ml emptied) and sucrose (3.11 +/- 0.1 ml emptied) compared with control (3.75 +/- 0.2 and 2.28 +/- 0.1 ml emptied for NaCl and sucrose loads, respectively). In contrast, ICV MK-801 did not alter NaCl emptying (3.82 +/- 0.1 ml emptied) compared with control (3.82 +/- 0.3 ml emptied) and actually reduced gastric emptying of sucrose (2.1 +/- 0.2 and 2.94 +/- 0.1 ml emptied, for MK and vehicle, respectively). These data confirm previous results that systemic as well as hindbrain injection of MK-801 increases food intake. However, because ICV MK-801 failed to increase gastric emptying, these results indicate that MK-801 increases food intake through mechanisms independent of altered gastric emptying.     

Centrally administered neuropeptide Y delays gastric emptying via Y2 receptors in rats

It has been shown that centrally administered neuropeptide Y (NPY) delays gastric emptying. To determine the receptor subtypes of NPY mediating the inhibitory effects on gastric emptying, effects of intracerebroventricular injection of NPY, [Leu31,Pro34]NPY (a Y1 agonist) and NPY-(3-36) (a Y2 agonist) on solid gastric emptying and postprandial antropyloric motility were studied in conscious rats. Intracerebroventricular injection of NPY and NPY-(3-36), but not [Leu31,Pro34] NPY, delayed solid gastric emptying in a dose-dependent manner (0.03-3 nmol). After the feeding (40 min), contractions with low frequency and high amplitude of the antrum were frequently observed, and the peak contraction of the antrum occurred most often 3-6 s before the peak contraction of the pylorus. Intracerebroventricular injection of NPY and NPY-(3-36) (3 nmol), but not [Leu31,Pro34]NPY, significantly reduced antral contractions and the number of antropyloric coordination events. It is suggested that centrally administered NPY impairs postprandial antral contractions and antropyloric coordination via Y2 receptors, resulting in delayed gastric emptying.     

Inhibitory effects of desvenlafaxine on gastric slow waves, antral contractions, and gastric accommodation mediated via the sympathetic mechanism in dogs

Desvenlafaxine succinate (DVS; Pristiq) is a new antidepressant, serotonin-norepinephrine reuptake inhibitor. Antidepressants have been widely used for the treatment of functional gastrointestinal disorders. Possible roles of DVS on gastrointestinal motility have not been studied. The aim of this study was to investigate the effects of DVS on gastric slow waves (GSW), antral contractions, and gastric accommodation in dogs. Fifteen healthy dogs implanted with gastric serosal electrodes and a gastric cannula were studied in four separate sessions: control, DVS (50 mg), propranolol (1 mg·kg(-1)·h(-1)), and propranolol + DVS. GSW were measured via the gastric serosal electrodes. Antral contractions were assessed via an intraluminal manometric catheter inserted via the gastric cannula. The sympathovagal activity was assessed from the spectral analysis of the heart rate variability signal. Gastric tone was measured by barostat via an intragastric balloon inserted into the fundus via the gastric cannula. In the postprandial period, in comparison with the control, DVS reduced the percentage of normal GSW (P=0.001) and increased the percentage of tachygastria (P=0.005) and bradygastria (P=0.002). Simultaneously, DVS increased the sympathetic activity (P=0.006) and the sympathovagal ratio (low frequency/high frequency; P=0.044). These effects were blocked by propranolol. DVS attenuated postprandial antral contractions and gastric accommodation. The postprandial antral contractile index (area under the curve) was decreased by 26% with DVS (P=0.013), and gastric accommodation was decreased by about 50% with DVS (P < 0.001). The inhibitory effect of DVS on gastric accommodation was blocked by propranolol. DVS inhibits gastric contractions, slow waves, and accommodation in the fed state. These inhibitory effects are associated with an increased sympathetic modulation in the gastrointestinal system. Cautions should be made when DVS is used for treating patients with depression and gastric motility disorders.     

Exenatide can reduce glucose independent of islet hormones or gastric emptying

Exenatide is a long-acting glucagon-like peptide-1 (GLP-1) mimetic used in the treatment of type 2 diabetes. There is increasing evidence that GLP-1 can influence glycemia not only via pancreatic (insulinotropic and glucagon suppression) and gastric-emptying effects, but also via an independent mechanism mediated by portal vein receptors. The aim of our study was to investigate whether exenatide has an islet- and gastric-independent glycemia-reducing effect, similar to GLP-1. First, we administered mixed meals, with or without exenatide (20 microg sc) to dogs. Second, to determine whether exenatide-induced reduction in glycemia is independent of slower gastric emptying, in the same animals we infused glucose intraportally (to simulate meal test glucose appearance) with exenatide, exenatide + the intraportal GLP-1 receptor antagonist exendin-(9-39), or saline. Exenatide markedly decreased postprandial glucose: net 0- to 135-min area under the curve = +526 +/- 315 and -536 +/- 197 mg.dl(-1).min(-1) with saline and exenatide, respectively (P < 0.05). Importantly, the decrease in plasma glucose occurred without a corresponding increase in postprandial insulin but was accompanied by delayed gastric emptying and lower glucagon. Significantly lower glycemia was induced by intraportal glucose infusion with exenatide than with saline (92 +/- 1 vs. 97 +/- 1 mg/dl, P < 0.001) in the absence of hyperinsulinemia or glucagon suppression. The exenatide-induced lower glycemia was partly reversed by intraportal exendin-(9-39): 95 +/- 3 and 92 +/- 3 mg/dl with exenatide + antagonist and exenatide, respectively (P < 0.01). Our results suggest that, similar to GLP-1, exenatide lowers glycemia via a novel mechanism independent of islet hormones and slowing of gastric emptying. We hypothesize that receptors in the portal vein, via a neural mechanism, increase glucose clearance independent of islet hormones.     

Dual effects of acupuncture on gastric motility in conscious rats

The effects of manual acupuncture on gastric motility were investigated in 35 conscious rats implanted with a strain gauge transducer. Twenty (57.1%) rats showed no cyclic groupings of strong contractions (type A), whereas 15 (42.9%) rats showed the phase III-like contractions of the migrating motor complex (type B) in the fasting gastric motility. Acupuncture at the stomach (ST)-36 (Zusanli), but not on the back [Weishu, bladder (BL)-21], increased the peak amplitude of contractions to 172.4 +/- 25.6% of basal in the type A rats (n = 20, P < 0.05). On the other hand, the motility index for 60 min after the acupuncture was not affected by the acupuncture in this group. On the contrary, acupuncture decreased the peak amplitude and motility index to 72.9 +/- 14.0% and 73.6 +/- 16.2% in the type B rats (n = 15, P < 0.05), respectively. The stimulatory and inhibitory effects of acupuncture observed in each type were reproducible on the separate days. In 70% of type A rats, acupuncture induced strong phase III-like contractions lasting for over 3 h that were abolished by atropine, hexamethonium, atropine methyl bromide, and vagotomy. Naloxone significantly shortened the duration of the stimulatory effects from 3.52 +/- 0.21 to 1.02 +/- 0.15 h (n = 3, P < 0.05). These results suggest that acupuncture at ST-36 induces dual effects, either stimulatory or inhibitory, on gastric motility. The stimulatory effects are mediated in part via vagal efferent and opioid pathways.     

Influence of sildenafil on gastric sensorimotor function in humans

After a meal, the proximal stomach relaxes probably through the activation of nitrergic neurons in the gastric wall. Nitric oxide-induced smooth muscle relaxation involves activation of soluble guanylate cyclase, with cGMP production, which is then degradated by phosphodiesterase-5 (PDE-5). The aim of this study was to investigate the effect of sildenafil, a selective PDE-5 inhibitor, on fasting and postprandial proximal gastric volume and on gastric emptying rates in humans. A gastric barostat was used to study gastric compliance and perception to isobaric distension in healthy subjects before and after placebo (n = 13) or sildenafil, 50 mg (n = 15). In 10 healthy subjects, two gastric barostat studies were performed in randomized order to study the effect of placebo or sildenafil on postprandial gastric relaxation. Similarly, solid and liquid gastric emptying rates were studied in 12 healthy subjects. Sildenafil significantly increased fasting intragastric volume (141 +/- 15 vs. 163 +/- 15 ml, P < 0.05) and volumes of first perception. Sildenafil induced a higher and prolonged gastric relaxation either at 30 min (357 +/- 38 vs. 253 +/- 42 ml, P < 0.05) or 60 min (348 +/- 49 vs. 247 +/- 38 ml, P < 0.05) after the meal. Sildenafil did not alter solid half-emptying time but significantly delayed liquid emptying (43 +/- 4 vs. 56 +/- 4 min, P < 0.01). In conclusion, sildenafil significantly increases postprandial gastric volume and slows liquid emptying rate, confirming that meal-induced accommodation in humans involves the activation of a nitrergic pathway. The effect of sildenafil on gastric fundus suggests a therapeutic potential for phosphodiesterase inhibitors in patients with impaired gastric accommodation.     

Electroacupuncture improves impaired gastric motility and slow waves induced by rectal distension in dogs

Rectal distension (RD) is known to induce upper gastrointestinal (GI) symptoms. The aim of this study was to investigate the effects and underlying mechanisms of RD on gastric slow waves (GSW) and motor activity and furthermore to investigate the effects and mechanisms of electroacupuncture (EA) on GSW and motor activity. Eight female hound dogs chronically implanted with gastric serosal electrodes and a gastric fistula were studied in six separate sessions. Antral motility, GSW, heart rate variability, and rectal pressure were evaluated for the above purposes. 1) RD at a volume of 120 ml suppressed antral motility significantly. Guanethidine blocked the inhibitory effect of RD. EA at ST36 was able to restore the suppressed antral contractions induced by RD (16.6+/-1.7 vs. 8.0+/-1.4, P<0.001). Naloxone partially blocked the effect of EA on antral contractions. 2) RD reduced the percentage of normal GSW from 98.8+/-0.8% at baseline to 76.1+/-8.6% (P<0.05) that was increased to 91.8+/-3.0% with EA. The effects of EA on the GSW were nullified by the presence of naloxone. 3) EA did not show any significant effect on rectal pressure, suggesting that the ameliorating effects of EA on RD-induced impaired gastric motility were not due to a decrease in rectal pressure. 4) EA increased the vagal activity suppressed by RD. In conclusion, RD inhibits postprandial gastric motility and impairs GSW in dogs, and the inhibitory effects are mediated via the adrenergic pathways. EA at ST36 is able to restore the RD-induced impaired GSW and motor activities, possibly by enhancing vagal activity, and is partially mediated via the opioid pathway. EA may have therapeutic potential for functional gastrointestinal disorders.     

Vagally induced gastric antral contractions and gastric emptying of a liquid test meal.

The emptying of a liquid test meal from the stomach was studied during, and in the absence of, electrical stimulation of cut ends of a thoracic branch of the vagus in anaesthetized cats. The test meal (154 mmol.1-1 NaCl and 30 mg.1-1 phenol red) was measured by collecting effluent from a duodenal fistula over a 30 min period. The stomach emptied about 60% of the meal under control conditions compared with over 90% during efferent stimulation of the vagus. The increased volumes emptied during efferent stimulation were not accounted for by secretion of gastric acid. Coincident with the vagally evoked antral contractions there was a gush of liquid from the duodenal cannula. Afferent vagal stimulation resulted in an initial marked delay of emptying followed by an acceleration so that the volume emptied after 30 min was similar to that in control experiments. Antral contractions, evoked by efferent vagal stimulation, accelerated the emptying of a liquid test meal from the stomach.     

Gastric inhibitory polypeptide does not inhibit gastric emptying in humans

The insulinotropic gut hormone gastric inhibitory polypeptide (GIP) has been demonstrated to inhibit gastric acid secretion and was proposed to possess "enterogastrone" activity. GIP effects on gastric emptying have not yet been studied. Fifteen healthy male volunteers (23.9 +/- 3.3 yr, body mass index 23.7 +/- 2.3 kg/m(2)) were studied with the intravenous infusion of GIP (2 pmol.kg(-1).min(-1)) or placebo, each administered to the volunteers on separate occasions from -30 to 360 min in the fasting state. At 0 min, a solid test meal (250 kcal containing [(13)C]sodium octanoate) was served. Gastric emptying was calculated from the (13)CO(2) exhalation rates in breath samples collected over 360 min. Venous blood was drawn in 30-min intervals for the determination of glucose, insulin, C-peptide, and GIP (total and intact). Statistical calculations were made by use of repeated-measures ANOVA and one-way ANOVA. During the infusion, GIP rose to steady-state concentrations of 159 +/- 15 pmol/l for total and 34 +/- 4 pmol/l for intact GIP (P < 0.0001). Meal ingestion further increased GIP concentrations in both groups, reaching peak levels of 265 +/- 20 and 82 +/- 9 pmol/l for total and 67 +/- 7 and 31 +/- 9 pmol/l for intact GIP during the administration of GIP and placebo, respectively (P < 0.0001). There were no differences in glucose, insulin, and C-peptide between the experiments with the infusion of GIP or placebo. Gastric half-emptying times were 120 +/- 9 and 120 +/- 18 min (P = 1.0, with GIP and placebo, respectively). The time pattern of gastric emptying was similar in the two groups (P = 0.98). Endogenous GIP secretion, as derived from the incremental area under the curve of plasma GIP concentrations in the placebo experiments, did not correlate to gastric half-emptying times (r(2) = 0.15, P = 0.15 for intact GIP; r(2) = 0.21, P = 0.086 for total GIP). We conclude that gastric emptying does not appear to be influenced by GIP. The secretion of GIP after meal ingestion is not suppressed by its exogenous administration. The lack of effect of GIP on gastric emptying underlines the differences between GIP and the second incretin glucagon-like peptide 1.     

Fixed feeding potentiates interdigestive gastric motor activity in rats: importance of eating habits for maintaining interdigestive MMC

Endogenous ghrelin regulates the occurrence of interdigestive gastric phase III-like contractions in rats. However, the fasted motor pattern is not as regular and potent in humans and dogs. We hypothesize that eating habits play an important role in maintaining a regular interdigestive gastric contractions. We studied the effect of fixed-feeding regimen on interdigestive gastric contractions and plasma acyl ghrelin levels. The fixed-fed rats were trained to the assigned meal feeding regimen, once daily at 12:00 PM to 4:00 PM for 14 days. Free-fed rats were maintained with free access to food. As ghrelin regulates gastric emptying as well, solid gastric emptying was also studied in fixed-fed rats and free-fed rats. In free-fed rats, two of six rats did not show interdigestive gastric phase III-like contractions. In contrast, phase III-like contractions were observed in all rats 14 days after starting the fixed-feeding regimen. The maximal amplitude of phase III-like contractions significantly increased from 8.4 +/- 0.6 to 16.3 +/- 1.8 g (n = 6, P < 0.05) 14 days after the start of the fixed feeding. Fasted and postprandial plasma ghrelin levels were significantly increased after 14 days of fixed feeding. Solid gastric emptying was significantly accelerated in fixed-fed rats (72.1 +/- 4.2%) compared with that of free-fed rats (58.7 +/- 2.7%, n = 6, P < 0.05). Our present findings suggest that fixed feeding increases plasma ghrelin levels, potent interdigestive contractions, and acceleration of gastric emptying.     

Mechanical factors regulating gastric emptying examined by the effects of exogenous cholecystokinin and secretin on canine gastroduodenal motility

The aim of this study was to elucidate the variables of gastroduodenal motility determining gastric emptying. For this purpose the effects of exogenous cholecystokinin, secretin, and gastric inhibitory polypeptide on motility and gastric emptying were studied during a meal. Motility was measured with extraluminal strain gage force transducers and induction coils in unanaesthetized dogs. The pyloric diameter and the duodenal lumen were evaluated from radiographs. Gastric emptying of an acaloric cellulose meal was determined radiographically. When compared with control infusion of saline, cholecystokinin (1.7 Ivy units X kg-1 X h-1) and secretin (1.7 clinical units X kg-1 X h-1) delayed gastric emptying and diminished the force of the antral contractions, the force and frequency of the duodenal contractions, and opening of the pylorus. The contractile patterns of the duodenum were changed from propulsive to segmenting activity. Cholecystokinin additionally diminished the duodenal lumen. In contrast, gastric inhibitory polypeptide (1.5 microgram X kg-1 X h-1) did not influence gastroduodenal motility and gastric emptying. It is concluded that the motility parameters that were significantly altered by cholecystokinin and secretin are involved in the control of gastric emptying, while other parameters that remained unchanged play a minor role in the regulating process.