Plasma Gastrin Concentrations Research Articles

Effects of Differently Composed Feeds and Physical Stress on Plasma Gastrin Concentration in Horses

Plasma gastrin concentrations were determined in 6 Standardbreds (4 geldings and 2 mares) after 3 different meals consisting of unlimited amounts of hay (8-9 kg per horse), a restricted amount of hay (0.6 kg/100 kg body-weight) and grain (0.2 kg/100 kg body-weight) in combination or of grain alone (0.2 kg/100 kg body-weight). In another series of experiments the possible role of gastrin as a stress hormone was investigated. Plasma gastrin and cortisol concentrations were determined during fasting and compared with concentrations during hay feeding. In addition, gastrin and cortisol concentrations were determined before, during and after 2 kinds of physical exercise on a treadmill. Meal stimulation significantly increased the plasma gastrin concentration, irrespective of the meal composition. An immediate and large increase in plasma gastrin concentration was found when voluminous meals were given, whereas a small meal evoked a later onset of gastrin release, suggesting that gastric distention plays an important role in inducing gastrin release during a meal. Meals consisting of grain seem to evoke a slower onset and then a more prolonged gastrin response than a hay meal, possibly due to different emptying rates of the stomach. Nervous excitation may play a minor role in the activation of gastrin release in horses. No experimental support was obtained for the idea that gastrin acts as a stress hormone in the horse.

Comparison of the Kinetics of Pancreatic Secretion and Gut Regulatory Peptides in the Plasma of Preruminant Calves Fed Milk or Soybean Protein

Exocrine secretion from the pancreas and concentrations of cholecystokinin, gastrin, secretin, and somatostatin in plasma were measured in relation to feeding in 70- to 120-d-old preruminant calves fed either a milk diet or a soybean diet. Pancreatic fluid was continuously collected, measured, and reintroduced in catheterized calves. Blood samples were withdrawn for measurements of gut regulatory peptide concentrations in plasma. A slight increase in outflow of pancreatic fluid was observed 30min before the milk diet was introduced but not before the soybean diet was fed. In contrast, concentrations and outflows of protein and trypsin immediately after feeding were higher when calves were fed the soybean diet. Overall, during the first 5h postfeeding, the outflow of pancreatic fluid was 40% higher when the milk diet was fed than when the soybean diet was fed. No difference in outflow of protein was observed, but that of trypsin was 82% higher when the soybean diet was fed. This enhanced enzyme secretion could have been related to the increased plasma concentrations of gastrin and cholecystokinin after the soybean diet was fed. Secretin release was less in calves fed the milk diet that in calves fed the soybean diet during the first 2h postfeeding, suggesting that this gut peptide along with gastrin and cholecystokinin, contributed to the stimulation of enzyme secretion. Plasma gut regulatory peptides could be influenced by the soybean diet, which does not coagulate in the stomach, inducing faster gastric emptying of protein and fat, and by the chemical form of protein from the soybean diet and the lower susceptibility of these proteins to protease compared with casein. However, the resulting enhancement of pancreatic trypsin secretion and activity seemed to be insufficient to increase the digestibility of soybean protein up to a level similar to that of milk.

Selective Nutrient Feeding Induces Maturation of Gastrointestinal Hormone Release in Preterm Infants • 1498

We have previously shown that preterm infants given small enteral feedings have higher plasma concentrations of gastrin and gastric inhibitory peptide(GIP), while plasma concentrations of peptide YY (PYY) are unchanged. In adults, the ingestion of protein stimulates the release of gastrin which, in turn, stimulates the release of acid and stimulates an increase in gastroduodenal motor activity. Carbohydrate stimulates the release of GIP which regulates plasma glucose and inhibits small intestinal motor activity. Fats stimulate the release of PYY which inhibits small intestinal motor activity. We speculated that feeding babies with selective nutrients would induce hormone release in preterm infants as they do in adults, and, thus, enhance gastrointestinal function. Eighty preterm infants 25 to 30 wks gestation admitted to the Newborn Intensive Care Unit at Ben Taub General Hospital were fed 24 ml/kg/d for the first 10 days they received enteral feedings in addition to parenteral nutrition. Infants were given one of 4 formulas: full 24 cal/oz formula (n=20), its carbohydrate (n=20), protein(n=20), or fat component (n=20), all fed in 4 hr cycles consisting of 2 hr infusions interrupted by 2 hrs of fasting. On the tenth study day, blood was drawn to determine fasting plasma concentrations of gastrin, GIP, and PYY. In addition, motor responses to a full strength formula feeding were assessed via a low compliance continuous perfusion manometry. Compared to values seen at birth, fasting plasma concentrations of gastrin increased by feeding day 10 among infants fed protein, fat, or full formula (all p<0.05, paired t test) but not carbohydrate. GIP plasma concentrations increased in babies fed carbohydrate or full formula (both p<0.05) but not fat or protein. Plasma concentrations of peptide YY did not change in any feeding group. No group of study infants displayed the presence of a motor response to feeding before enteral feedings were begun. Babies fed protein or full formula displayed motor responses to feeding after 10 days of feeding while babies fed carbohydrate and fat did not. We conclude that the release of gastrointestinal hormones in response to selective nutrients is present in preterm infants, as well as motor responses to feeding that are mediated by those nutrients. We speculate that designing formulas that trigger intestinal hormonal release may be useful in enhancing the infant's endogenous mechanisms to improve gastrointestinal function.

Effect of bombesin at low doses on the secretion of the exocrine pancreas and on plasma gastrin concentration in the conscious pig

We investigated the role of low-doses of bombesin in the regulation of exocrine secretion in the pancreas of the conscious pig. In ten growing castrated male Large White pigs, bombesin was infused intravenously for 1 h at doses of 0 to 500 pmol/kg/h under a stimulation of secretin (36 pmol/kg/h). In six pigs, bombesin (50 pmol/kg/h) was administered alone for 2 h and its effect on pancreatic secretion was compared to that of an infusion of secretin. The pancreatic juice and the blood were collected at 15-min intervals for use in assays of protein in the juice and gastrin in the plasma. When bombesin was infused alone or in combination with secretin, the volume secreted was not altered. The protein output was not altered by secretin, but was increased by the infusion of bombesin, in a dose-dependent manner, reaching a plateau at 250 pmol/kg/h. The plasma gastrin levels were increased by bombesin, starting with the 50 pmol/kg/h dose. This effect was maximal at a dose of 100 pmol/kg/h. The levels remained below those measured after a standard meal, demonstrating that the effect of bombesin on the studied parameters is of physiological significance.

Minimal Enteral Feedings Suppress Intestinal Mucosal Growth That Is Not Reversed by Glutamine Supplementation in Neonatal Dogs • 1545

The combination of parenteral nutrition and minimal enteral feedings (MEF), i.e. 10-20% of daily fluid intake, is commonly used in neonates to reduce the risk of necrotizing enterocolitis. We have previously shown that MEF enhances maturation of intestinal motor function but not gut growth in parenterally fed neonatal dogs (Pediatr Res 39:125A). Although glutamine has been shown in some studies to prevent mucosal atrophy, it has not been established whether its addition to MEF can enhance gut growth in healthy gut. Our hypothesis was that MEF+Glutamine would enhance gut growth as well as maturation of motor function. Methods: We placed central venous catheters in 31 newborn puppies from 6 litters who were given 200 ml/kg/d parenterally. Puppies were then randomly assigned to 4 groups: No enteral feeds(NPO), MEF(20 ml/kg/d), MEF+Glutamine and MEF+Glutamate (to control for protein intake). Enteral feeds were comprised of a pooled mixture (1:1) of canine and human milk enriched with either glutamine or glutamate at 0.4g/10 ml (800 mg/kg/d). Pups were gavage fed 5 times daily for 4 days and the volume of parenteral nutrition was reduced in the 3 MEF groups by the volume of enteral feedings given. Fluid intake was adjusted daily for weight gain. After 4 days, motor activity was then recorded for 2 hr and blood samples drawn for motilin and gastrin concentrations. Abdominal organs were then harvested for physical/biochemical assessment of growth. Results: There were no differences among the 4 groups with respect to overall weight gain or weight of stomach, intestine, liver or intestinal length. The DNA content (mg/kg body wt.) in duodenum and the protein contents of the duodenum, jejunum and ileum of the fed groups were all significantly lower compared to those seen in the NPO group(ANOVA/Fishers; all p<0.05). There were no significant differences in plasma gastrin or motilin concentrations. The duration of migrating motor activity was significantly higher in the Glutamine supplemented group compared to the Glutamate or NPO groups but not from MEFgroup. Conclusion: Although enteral glutamine does not augment maturation of motor function beyond that induced by MEF, enteral glutamate appears to suppress it. Minimal enteral feedings with or without glutamine or glutamate supplementation does not cause body or organ weight changes; indeed, MEF decreased mucosal growth. We speculate that enteral feeds may challenge the intestinal mucosa by causing local inflammatory responses which prevents growth.

Helicobacter pylori and somatostatin cells.

Tham et al. show that Helicobacter pylori infection lowers the density of immunoreactive somatostatin cells (D-cells) in the antral mucosa and elevates plasma gastrin concentrations. According to current hypothesis, the lack of inhibition by somatostatin allows excessive release of gastrin, which stimulates acid secretion and thus causes duodenal ulcers. The cytokine tumour necrosis factor-alpha which is released in H. pylori gastritis inhibits D-cells in culture and may be responsible. Why do not all infected persons get duodenal ulcers? Recent work shows that more aggressive strains of H. pylori have greater effects on somatostatin/gastrin physiology. Another variable is whether the infection causes corpusitis or not. Inflammation of the gastric corpus diminishes acid secretion, which greatly decreases the likelihood of duodenal ulcers but increases the risk of gastric cancer. Factors which promote corpusitis include diets with high salt content or lacking in antioxidant vitamins. Work in this area is elucidating how H. pylori causes different diseases. Hopefully this will allow us to predict and prevent its serious sequelae.

Effect of sham feeding and acute suppression of acid secretion on human gastric lipase secretion.

Gastric lipase and gastric acid are secreted simultaneously. The aim of this study was to investigate whether the acid interferes with the lipase secretion. The secretion of human gastric lipase was studied during blockade of gastric acid secretion and modified sham feeding to estimate the impact of these conditions on both gastric lipase enzyme activity and immunoreactivity. Eight healthy volunteers were intubated with a nasogastric tube. We examined gastric aspirates for the amount and activity of lipase secretion during basal conditions, after blockade of acid secretion with a proton pump inhibitor (omeprazole iv. infusion), and in response to sham feeding (chewing gum) during the blockade. The amount of secreted gastric lipase was unaffected by blockade of acid secretion and increased significantly after sham feeding (169.9+/-35.7 microg/15 min to 348.1+/-79.2 microg/15 min; p < 0.01). Likewise, the output of enzyme activity increased after sham feeding (0.63+/-0.09 kU/15 min to 1.52+/-0.36 kU/15 min; p < 0.03). The concentration of enzyme activity remained unchanged by blockade of acid secretion, whereas the output of enzyme activity was decreased, probably because of reduced volume secretion or denaturation and conformational changes of the enzyme. Plasma concentrations of gastrin increased in response to blockade of acid secretion (basal 9.6+/-1.4 pmol/L to 13.3+/-2.9 pmol/L; p < 0.02). Gastric acid secretion is not a prerequisite for gastric lipase secretion. Lipase enzyme activity, though, is sensitive to anacidic conditions.

Effect of sham feeding and acute suppression of acid secretion on human gastric lipase secretion

Objective: Gastric lipase and gastric acid are secreted simultaneously. The aim of this study was to investigate whether the acid interferes with the lipase secretion. The secretion of human gastric lipase was studied during blockade of gastric acid secretion and modified sham feeding to estimate the impact of these conditions on both gastric lipase enzyme activity and immunoreactivity. Methods: Eight healthy volunteers were intubated with a nasogastric tube. We examined gastric aspirates for the amount and activity of lipase secretion during basal conditions, after blockade of acid secretion with a proton pump inhibitor (omeprazole i.v. infusion), and in response to sham feeding (chewing gum) during the blockade. Results: The amount of secreted gastric lipase was unaffected by blockade of acid secretion and increased significantly after sham feeding (169.9 ± 35.7 μg/15 min to 348.1 ± 79.2 μg/15 min; p < 0.01). Likewise, the output of enzyme activity increased after sham feeding (0.63 ± 0.09 kU/15 min to 1.52 ± 0.36 kU/15 min; p < 0.03). The concentration of enzyme activity remained unchanged by blockade of acid secretion, whereas the output of enzyme activity was decreased, probably because of reduced volume secretion or denaturation and conformational changes of the enzyme. Plasma concentrations of gastrin increased in response to blockade of acid secretion (basal 9.6 ± 1.4 pmol/L to 13.3 ± 2.9 pmol/L; p < 0.02). Conclusions: Gastric acid secretion is not a prerequisite for gastric lipase secretion. Lipase enzyme activity, though, is sensitive to anacidic conditions.

Inhibition of human gastric lipase secretion by glucagon-like peptide-1.

Glucagon-like peptide-1 (GLP-1) may be one of the enterogastrone hormones of the ileal brake mechanism. We therefore studied its effects on gastric lipase secretion in healthy volunteers and vagotomized patients during infusion of pentagastrin. The intestinal incretin hormone GLP-1 (glucagon-like peptide-1, 7-36 amide) was investigated because of its inhibitory effects on gastric acid secretion and motility. GLP-1 infused intravenously in amounts corresponding to the postprandial release significantly inhibited pentagastrin-stimulated gastric lipase secretion and lipolytic activity. The inhibitory effect of GLP-1 persisted in vagotomized patients, suggesting that fundic chief cells, from which gastric lipase is released, or neighboring inhibitory cells could be equipped with GLP-1 receptors. Vagotomized patients had significantly higher plasma concentrations of gastrin and secretin. No significant changes of gastrin, secretin, and CCK secretion were seen during GLP-1 infusion in the vagotomized patients, whereas secretin decreased significantly in the healthy volunteers. GLP-1 seems to be a naturally occurring inhibitor of gastric lipase secretion acting via a nonvagal mechanism. Our results indicate that gastric lipase secretion is subject to hormonal stimulatory as well as inhibitory mechanisms.

The role of melatonin and L-tryptophan in prevention of acute gastric lesions induced by stress, ethanol, ischemia, and aspirin.

Melatonin, a pineal hormone, synthesized from L-tryptophan, is known to exist in the gut and to scavenge oxygen free radicals but its role in gastroprotection against acute lesions induced by various strong irritants has been little studied. In this study, we determined the effects of melatonin and L-tryptophan on gastric secretion and the formation of acute gastric lesions induced by absolute ethanol, acidified aspirin (ASA), stress, and ischemia-reperfusion (I/R). Area of gastric lesions was determined by planimetry, gastric blood flow (GBF) was measured using a H2-gas clearance technique, and blood was withdrawn for the measurement of free radicals, plasma gastrin, and melatonin concentration by specific radioimmunoassay. Intragastric (i.g.) administration of melatonin (2.5-10 mg/kg) or L-tryptophan (25-200 mg/kg) failed to affect gastric lesions by ethanol and ASA but dose-dependently reduced the lesions provoked by stress and I/R; this protective effect was accompanied by a significant rise in plasma melatonin level, GBF, and DNA synthesis and by a marked fall in blood free radicals. L-tryptophan, which significantly elevated the plasma melatonin by about 3-5-fold, also reduced the stress and I/R-induced lesions and blood levels of free radicals, while increasing the GBF, DNA synthesis, and plasma gastrin levels. Inhibition of mucosal generation of PGE2 by indomethacin abolished the protection and the rise of GBF afforded by melatonin and L-tryptophan, whereas pretreatment with N(G)-nitro-L-arginine (L-NNA), to suppress nitric oxide (NO) synthase, was without any effect. We conclude that melatonin applied exogenously in pharmacological doses and that released by the administration of its precursor, L-tryptophan, protect gastric mucosa from the damage induced by stress and I/R possibly by a mechanism involving the scavenging of free radicals and gastric hyperemia probably mediated by endogenous prostaglandin but not NO.

Increased sensitivity of gastrin cells to gastric distension following antral denervation in the rat.

1. Secretion of the antral hormone gastrin is increased by protein in the gastric lumen and by nervous reflexes. We have examined the relative importance of luminal and neuronal mechanisms, by lesioning the antral innervation using benzalkonium chloride. 2. Benzalkonium chloride was applied to the serosa of the antrum in anaesthetized rats. In some animals, a stainless-steel cannula was also implanted in the corpus. Animals were allowed 10 days to recover. Plasma gastrin was measured by radioimmunoassay and mRNAs encoding gastrin, somatostatin and histidine decarboxylase were measured by Northern blot. 3. Antral denervation was associated with gastric retention after fasting, and elevated plasma gastrin (28.4 +/- 7 pM compared with 7.6 +/- 1.0 pM in controls). When fasted control or denervated rats were refed, plasma gastrin increased 3-fold in both cases. A gastrin-releasing peptide antagonist inhibited the post-prandial rise in plasma gastrin in control rats, but had no effect in antrally denervated rats. 4. In fasted, antrally denervated rats with a gastric fistula, basal gastric acid secretion was depressed 3-fold, and plasma gastrin concentrations were similar to controls. 5. Distension of the stomach with peptone via a barostat attached to the gastric cannula (5 cm H2O, 30 min), produced 3-fold increases in plasma gastrin in both control and denervated rats. However, distension with a non-nutrient solution at pH 6.0 had no effect in controls, but increased gastrin to a similar extent to peptone in denervated rats; distension with 50 mM HCl had no effect in either control or denervated rats. 6. Somatostatin and gastrin mRNA abundances in the antrum were depressed by about 35% by antral denervation, but somatostatin mRNA in the corpus was unchanged; GAPDH mRNA abundance was unaffected by antral denervation. 7. The data suggest that luminal nutrient releases gastrin in the rat, in vivo, via activation of antral neurons secreting gastrin-releasing peptide, and that the antral innervation normally inhibits G-cell responses to non-nutrient distension of the stomach. After antral denervation, gastric distension with a non-nutrient solution is an adequate stimulus for gastrin release.

Regulation by gastric acid of the processing of progastrin-derived peptides in rat antral mucosa.

1. Inhibition of gastric acid secretion by proton pump inhibitors like omeprazole increases the synthesis and secretion of the pyloric antral hormone gastrin. We report here how omeprazole influences the conversion of the gastrin precursor to its final products, and the abundance of mRNAs encoding proteins associated with progastrin processing in rat antral mucosa. 2. Progastrin processing was studied using a pulse-chase protocol in antral mucosa, incubated in vitro, from rats treated with omeprazole for up to 5 days. Labelled peptides were detected by on-line scintillation counting after immunoprecipitation and HPLC. The mRNAs encoding prohormone-processing enzymes were identified by Northern blot, polymerase chain reaction or ribonuclease protection assay, and their cellular origins identified by immunocytochemistry. 3. Cleavage of [3H]- and [35S]-labelled progastrins at Arg-94-95 or Arg-57-58, and amidation at Phe-92 were not influenced by pretreatment with omeprazole. In contrast, cleavage of G34 (the thirty-four amino acid amidated gastrin) at Lys-74-75 to give G17 (the seventeen amino acid amidated gastrin), and of G34-Gly to G17-Gly (G34 and G17 with COOH-terminal glycine), was increased 3-fold after treatment with omeprazole for either 1 or 5 days. 4. Approximately 20% of newly synthesized amidated and Gly-extended gastrins were secreted within 240 min of the labelling period in omeprazole-treated samples, but secretion of labelled gastrins from control tissue was undetectable over a comparable period. 5. The amidating enzyme, peptidyglycine alpha-amidating mono-oxygenase (PAM), the prohormone convertases PC1/3, PC2, PC5 and the PC2 chaperone 7B2 were localized to rat antral gastrin cells by immunocytochemistry. The relative abundance of mRNA species encoding 7B2, PC5 and PAM were unchanged after treatment with omeprazole for 5 days, whereas gastrin, PC1/3 and PC2 mRNAs are known to increase at this time. 6. The main consequence of increased cleavage at Lys-74-75 is the production of G17 and G17-Gly at the expense of G34 and G34-Gly, respectively. The latter have longer plasma half-lives, and so their increased cleavage may serve to limit the rise in plasma gastrin concentration after inhibition of acid secretion. Changes in the abundance of mRNAs encoding prohormone-processing enzymes cannot account for the rapidity of the changes in cleavage of progastrin at Lys residues after omeprazole.

The effect of gastrin-releasing peptide on gastrin and somatostatin messenger RNAs in humans infected with Helicobacter pylori

BACKGROUND & AIMS: Gastrin-releasing peptide stimulates gastrin secretion but also inhibits its release via somatostatin. Exogenous gastrin-releasing peptide stimulates a greater increase in plasma gastrin concentrations in patients infected with Helicobacter pylori than in uninfected controls. Because this infection suppressed gastric mucosal somatostatin, we studied whether the increased gastrin response was a result of an abnormal response of the somatostatin cell. METHODS: Patients without dyspeptic ulcers received an infusion of either gastrin-releasing peptide or saline on separate occasions. Acid secretion was measured, and gastric biopsy specimens were taken for gastrin and somatostatin messenger RNA (mRNA) analysis and H. pylori diagnosis. RESULTS: In response to gastrin-releasing peptide, the increase in plasma gastrin concentrations in the infected patients was significantly higher than in the uninfected. Antral gastrin mRNA also increased significantly in the infected group but decreased significantly in the uninfected group. Basal somatostatin was lower in the infected group; gastrin-releasing peptide produced a significant increase in antral somatostatin mRNA concentration in infected, but not uninfected, patients. CONCLUSIONS: The somatostatin cell responds to gastrin-releasing peptide in H. pylori infection. Gastrin-releasing peptide normally inhibits gastrin mRNA expression, but inhibition is deficient in H. pylori infection, possibly because of low stimulated somatostatin levels. (Gastroenterology 1997 Jun;112(6):1940-7)

Kinetics of pancreatic exocrine secretion and plasma gut regulatory peptide release in response to feeding in preruminant and ruminant calves.

Pancreatic exocrine secretion and plasma cholecystokinin, gastrin, secretin, and somatostatin concentrations were examined in relation to feeding in 70- to 120-day-old preruminant and ruminant calves. The apparatus used was designed to immediately re-infuse the animal's own pancreatic juice and to carry out accurate measurements of the juice flow in real time and to take samples. In the preruminants, pancreatic juice, protein, and trypsin flows increased from 45 min before and until 15 min after the meal and decreased sharply thereafter over a period of 30 min. while protein and trypsin concentrations peaked after feeding. A significant increase in plasma gastrin and cholecystokinin (CCK), a fall in secretin and no change in somatostatin were observed after milk ingestion. By contrast, in the ruminants, feeding had no effect on the pancreatic secretion and on the plasma concentrations of these peptides. Similar and simultaneous patterns of juice flow and secretin, as well as of protein and trypsin concentrations, CCK and gastrin, could support the hypothesis that these gut regulatory peptides play a significant role in the regulation of the pancreatic function. In preruminant calves, the existence of cephalic, gastric and intestinal phases is discussed. In the ruminants, that of the ruminal phase is questionable.

Role of gastrin/CCK-B receptors in meal-stimulated acid secretion in rats.

Gastrin is the principal hormonal mediator of gastric acid secretion. Using an in vivo, intact, anesthetized rat model, we studied the role of gastrin/cholecystokinin (CCK)-B receptors in regulating the release of histamine and somatostatin during intragastric stimulation of acid secretion during a peptone meal. In pylorusligated, adult male rats (each implanted with a gastric cannula and portal venous and splenic artery catheters), after a 30-min basal period, gastric acid secretion was stimulated for 90 min either by an intravenous infusion of gastrin-17 (15 micrograms.kg-1.h-1) or by extragastric titration of 5 ml 8% peptone meal at pH 5.5. Basal and stimulated acid outputs and portal venous plasma gastrin, histamine, and somatostatin concentrations were measured before and after close-arterial injection of a new, relatively selective, gastrin/CCK-B receptor antagonist GR143330X. GR143330X reduced basal acid output by 50% but not basal plasma gastrin, histamine, or somatostatin concentrations. GR143330X reduced gastrin-stimulated acid output by 80%, plasma histamine by 70%, and plasma somatostatin by 34%. During intragastric peptone meal stimulation GR143330X reduced the acid response by 42% during the 30- to 60-min period but not during the 60- to 90-min period. GR143330X reduced the plasma histamine response by 72 and 68%, and the plasma somatostatin response by 32 and 54% during the 30- to 60- and 60- to 90-min periods, respectively. GR143330X did not block the gastrin response to peptone at any time. These results indicate that GR143330X is an effective agent for blocking gastrin-stimulated acid secretion and histamine and somatostatin release in rats. Furthermore, we show for the first time in an intact, in vivo, anesthetized rat model that meal-stimulated activation of gastrin/CCK-B receptors stimulates acid secretion in part by regulating the release of histamine and somatostatin.

Effect of cimetidine on basal and postprandial plasma concentrations of cholecystokinin and gastrin in humans.

Cimetidine reduces the appetite and weight in healthy overweight subjects. Gastrointestinal regulatory peptides such as cholecystokinin (CCK) have been proposed to mediate the satiety signal from gut to brain. Therefore, the effect of cimetidine on basal and postprandial plasma concentrations of cholecystokinin and gastrin was studied. After an overnight fast, 12 healthy volunteers were given cimetidine (400 mg) on day 1, breakfast on day 2, and cimetidine 20 min before breakfast on day 3. Plasma concentrations of cholecystokinin and gastrin were measured by radioimmunoassay. Plasma cholecystokinin concentration increased with one major peak observed 30 min and one smaller peak observed 120 min after intake of cimetidine. The meal induced an increase in the plasma concentration of cholecystokinin, while cimetidine prior to the meal elicited a sustained postprandial cholecystokinin response. Cimetidine had no effect on the basal plasma concentration of gastrin. The meal induced an increase in the plasma concentration of gastrin, while cimetidine prior to the meal elicited a sustained postprandial gastrin response. In conclusion, cimetidine increases the basal concentration of plasma cholecystokinin and elicits a sustained postprandial response of both cholecystokinin and gastrin. At least the cholecystokinin response may be one mechanism by which cimetidine reduces the appetite.

Meal-induced secretion of gastrointestinal regulatory peptides is not affected by sleep.

The mechanisms responsible for the disruption of the migrating motor complex (MMC) by feeding are not fully understood. Sleep reduces the duration of the postprandial or fed pattern of motility in the intestine. This study was set out to determine if this effect is associated with sleep-induced changes in the secretion of regulatory peptides in response to food. Duodenojejunal motility was studied in 15 healthy ambulant subjects for 2 consecutive days. On one day identical solid meals were consumed in the morning and late in the evening, the latter followed by sleep. On the other day, identical liquid meals were infused into the stomach and the duodenum in the morning and late in the evening, the latter after the onset of sleep. Plasma concentrations of gastrin, neurotensin, peptide YY (PYY), pancreatic polypeptide (PP), motilin and glucose were monitored before and after meals. Sleep significantly shortened the duration of the fed pattern after the solid meal and even more so after the liquid meal. The plasma concentrations of all peptides, except motilin, increased significantly following each meal. Blood glucose levels rose after each meal, the changes being similar with all meals. Food-induced gastrointestinal regulatory peptides secretion and intestinal absorption of glucose are not affected by sleep. The vagal response to a meal, as indicated by PP release, is intact during sleep. The results support the importance of neural mechanisms in the modulation of the postprandial pattern of intestinal motility.

Gastric lipase secretion after sham feeding and cholinergic blockade.

Our purpose was to examine gastric lipase secretion after cephalic stimulation (sham feeding) and to examine the effect of cholinergic blockade. Eight healthy volunteers, four women and four men, age 21-58 years, were studied twice on separate days. They were sham fed with and without infusion of atropine. Gastric content was measured and the amount as well as the activity of gastric lipase output were determined. Plasma concentrations of gastrin, secretin, and cholecystokinin (CCK) were measured simultaneously by radioimmunoassays. Cephalic stimuli can evoke human gastric lipase secretion, and this effect was almost ablated by atropine blockade of cholinergic receptors. The concentrations of CCK and secretin in plasma were unaffected by sham feeding with or without atropine blockade, whereas gastrin was stimulated by sham feeding after atropine blockade. Gastric lipase secretion in man is apparently controlled by interacting vagal and hormonal mechanisms.

Deficient Gastric Lipase Secretion in Pancreatic Insufficiency

Background: Gastrin is an important stimulator of gastric lipase secretion in man. In advanced pancreatic insufficiency gastric lipases might compensate for the lack of pancreatic lipases, hut the role of gastrin in such compensation remains to be evaluated. The aim of this study was to examine the effect of gastrin on the gastric lipase secretion in patients with pancreatic insufficiency. Methods: Eight patients with pancreatic insufficiency secondary to alcohol abuse were studied, and six healthy subjects volunteered as controls for the study. All volunteers received identical doses of intravenous gastrin-17 (10, 30, and 60 pmol/kg/h). The gastric content was measured, using a nasogastric tube for aspiration, and the amount and activity of gastric lipase output were determined. Plasma concentrations of gastrin, secretin, and cholecystokinin were measured by radioimmunoassays. Results: The increased plasma levels of gastrin were accompanied by a dose-dependent increase in the amount and activity of gastric lipase in controls, but in the patients the response was almost abolished. Conclusions: Gastrin in postprandial concentrations does not influence the secretion of gastric lipase in patients with pancreatic insufficiency due to chronic pancreatitis.

A Double-Blind Placebo-Controlled Study on the Effects of Omeprazole on Gut Hormone Secretion and Gastric Emptying Rate

Background: The present study was designed to investigate whether an effect of omeprazole on gastric emptying is related to changes in the secretion of selected gut hormones. Methods: The studies were performed in healthy men after 10 days' treatment with 40 mg omeprazole daily/placebo. Food ingestion took place in a duodenal phase I, and the meal consisted of an omelette labelled with technetium Tc 99m, followed by 150 ml water labelled with indium In 111. Plasma concentrations of gastrin, cholecystokinin (CCK), and motilin were measured. Results: Pretreatment with omeprazole reduced gastric emptying rates. This applied to all variables and was most pronunced with regard to amounts of solid (median (95% confidence interval)) emptied at 180 min (71% (48-86) for omeprazole versus 96% (87-100) for placebo; P < 0.01). All median values of plasma gastrin concentrations from the omeprazole series were higher than the corresponding values from the placebo series, and omeprazole induced a tenfold increase in incremental integrated area (IIA, pmol/1 × 180 min) of the gastrin concentration curve (5250 (2570-9680) versus 575 (240-1485); P < 0.01). New findings include a lower postprandial secretion of CCK in the omeprazole series and, consequently, a difference in total integrated area (TIA, pmol/1 × 180 min) (88 (21-147) versus 217 (104-267); P < 0.05) and IIA (pmol/1 × 180 min) (52 (2-142) versus 165 (104-195); P < 0.05), respectively; a difference in IIA-30 (pmol/1 × 30 min) of plasma motilin concentrations (270 (140-595) (omeprazole) versus 460 (285-655); P < 0.05); and a direct relationship between the amounts of liquid emptied at 30 min and the corresponding TIA-30 of plasma motilin in the omeprazole (Rs = 0.667; P <0.05) and the placebo series (Rs = 0.767; P <0.05). Conclusion: Pretreatment with 40 mg omeprazole daily decreases the gastric emptying rates and has a substantial influence on the secretion of gastrin, motilin, and CCK. The finding of an omeprazole-induced decrease in CCK release may have clinical implications. Further investigation into the possible effect of proton-pump inhibitors on biliary tract motility and cholesterol solubilization in gallbladder bile is warranted.