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Background: Gastrointestinal (GI) dysmotility and autonomic neuropathy are common problems among diabetics with largely unknown aetiology. Many peptides are involved in the autonomic nervous system regulating the GI tract. The aim of this study was to examine if concentrations of oxytocin, cholecystokinin (CCK), gastrin and vasopressin in plasma differ between diabetics with normal function and dysfunction in GI motility., Methods: Nineteen patients with symptoms from the GI tract who had been examined with gastric emptying scintigraphy, oesophageal manometry, and deep-breathing test were included. They further received a fat-rich meal, after which blood samples were collected and plasma frozen until analysed for hormonal concentrations., Results: There was an increase in postprandial oxytocin plasma concentration in the group with normal gastric emptying (p = 0.015) whereas subjects with delayed gastric emptying had no increased oxytocin secretion (p = 0.114). Both CCK and gastrin levels increased after the meal, with no differences between subjects with normal respective delayed gastric emptying. The concentration of vasopressin did not increase after the meal. In patients with oesophageal dysmotility the basal level of CCK tended to be higher (p = 0.051) and those with autonomic neuropathy had a higher area under the curve (AUC) of gastrin compared to normal subjects (p = 0.007)., Conclusion: Reduced postprandial secretion of oxytocin was found in patients with delayed gastric emptying, CCK secretion was increased in patients with oesophageal dysmotility, and gastrin secretion was increased in patients with autonomic neuropathy. The findings suggest that disturbed peptide secretion may be part of the pathophysiology of digestive complications in diabetics.

The present study was designed to investigate how repeated injections of oxytocin influence plasma levels of vagally controlled hormones such as gastrin, cholecystokinin (CCK), insulin and somatostatin, as well as of endogenous oxytocin and glucose. Since oxytocin may enhance the activity of centrally located alpha2-adrenoreceptors, a second aim of this study was to explore whether these receptors are involved in the effects. For this purpose, oxytocin (1.0 mg/kg) or NaCl was given subcutaneously (s.c.) once a day during 5 days to male rats. Rats were decapitated 1, 3 and 10 days after the last injection, blood was collected and hormone levels were radioimmunoassayed. The oxytocin treatment caused an elevation of plasma levels of oxytocin 1 day (p < 0.05) but not 3 and 10 days after treatment. Gastrin levels were decreased on day 1, 3 and 10 (ANOVA; p < 0.01). In addition, both insulin and CCK levels were decreased in response to the oxytocin treatment when measured 3 and 10 days after the last injection (ANOVA; insulin p < 0.01, CCK p < 0.05). When the alpha2-adrenoreceptor agonist clonidine (2.5 microgram/kg intracerebroventricularly) was administered 3 days after the 5-day treatment period with oxytocin or saline, plasma levels of insulin and CCK increased significantly (p < 0.05) in the oxytocin-treated rats, when compared to saline-treated controls receiving clonidine only. No change in glucose or somatostatin levels was found in response to the oxytocin treatment. In conclusion, these results show that oxytocin induces long-lasting changes in plasma levels of gastrin, CCK and insulin, without affecting somatostatin or glucose levels. These effects may be mediated by changes in vagal nerve activity.

Objective: To explore the pattern of gastrointestinal hormonal variations in plasma and to relate this to possible pathophysiological mechanisms in functional dyspepsia., Method: There were 25 patients, 12 men and 13 women, aged 24 to 50 years, with recurrent functional dyspepsia, compared with community control subjects pair-wise, matched for age and sex. The subjects participated in a laboratory stress experiment with timed provocations. At fixed intervals, 22 samples of blood were drawn from each subject and frozen for later peptide analyses. Levels of gastrin, cholecystokinin (CCK), and somatostatin were measured by radioimmunoassay. Peptide levels were studied during a friendly greeting, a stress interview, and a food stimulation., Results: Mean hormone values did not differ between the groups. Smokers had lower mean CCK than nonsmokers. Patients with a high degree of dyspeptic symptoms during the week preceding the experiment had a higher mean somatostatin level than patients with a low degree of dyspeptic symptoms. Heartburn correlated positively with the mean somatostatin level. Mean gastrin correlated with body mass index. During the 15-minute stress interview, significant changes in peptide variations were noted: Gastrin increased in both patient and control group subjects. CCK levels increased in patients from 7.2 pmol/l (6.0-8.5) to 9.8 pmol/l (8.2-11.4), but not in control subjects (p < 0.04, two-way interaction). Somatostatin increased significantly earlier in patients than in the control subjects during the stress interview., Conclusions: A positive relationship was found between the mean level of somatostatin and the degree of dyspeptic symptoms. Gastrin, CCK, and somatostatin were all sensitive to an anxiety-provoking interview. CCK and somatostatin may possibly link psychological reactions to the pathophysiology of functional dyspepsia.

Newborn babies have higher concentrations of gastrointestinal hormones than adults. The aim of the present study was to investigate the relationship between age and plasma levels of the three peptides gastrin, cholecystokinin and somatostatin in healthy children aged 1-15 years. Gastrin, cholecystokinin and somatostatin concentrations were twice as high at 1-2 years of age compared with children older than 10 years. Significant negative correlations between age and hormone concentrations were established. It is suggested that these age-dependent differences are related to the growth rate and relative energy consumption during the early years of life.

Plasma gastrin and somatostatin concentrations were measured by radioimmunoassay in exclusively formula-fed infants and in breast-fed infants receiving supplementary formula during the first five postnatal days. Infants exclusively formula fed had a progressive increase in mean plasma gastrin concentration from 109 +/- 42 pmol/l (mean +/- SD) on the first day to 236 +/- 103 pmol/l on the fifth day after birth (p = 0.0001). Breast-fed infants receiving supplementary formula had similar hormone concentrations as formula-fed infants of corresponding postnatal age and they also had a significant increase in hormone levels from the first to the fifth day (p = 0.0001). A positive relationship was found between gastrin concentration and ingested milk volume: Rs = 0.51, n = 105, p = 0.0001. The high gastrin concentrations most probably reflect enhanced hormonal release from the gastrin-producing cells in response to increasing volumes of milk ingested by the infant. The mean plasma somatostatin concentration on the first day after birth was 18 +/- 6 pmol/l. No significant change occurred during the first five postnatal days, independent of feeding type.

The objective of the present study was to measure plasma concentrations of the gastrointestinal hormones gastrin, somatostatin and cholecystokinin in plasma of children with recurrent abdominal pain, since these hormones affect gastrointestinal function. Forty-four children (7-16 years old) with recurrent abdominal pain and 36 control children (matched for age and sex) participated in the study. In a blood sample collected after an overnight fast, gastrin, somatostatin and cholecystokinin concentrations were measured by radioimmunoassay. The children with recurrent abdominal pain had higher plasma cholecystokinin levels (p < 0.001) than the controls. Whether or not this aberration is related to the clinical symptoms of children with recurrent abdominal pain remains to be established.

The aim of the present study was to investigate whether gastrin, cholecystokinin (CCK) and somatostatin secretion can be influenced by sensory stimulation and if so, whether such effects are mediated via the vagal nerves. Male rats anaesthetized with chloral hydrate were exposed to three different stimuli, i.e. to low frequency (2 Hz) electrical stimulation of muscles via needles (electro-acupuncture), to thermal stimulation at 40 degrees C or to vibration at 100 Hz. The two former stimuli activate mainly small and medium sized myelinated fibres from muscles and skin respectively, whereas vibration activates large myelinated fibres from skin, subcutaneous tissue and muscles. Experiments were also performed on animals that were vagotomized or exposed to prior treatment with atropine (0.5 mg kg-1). Blood was collected at various time intervals and plasma levels of gastrin, CCK and somatostatin were measured with radioimmunoassay (RIA). All three stimuli, i.e. electro-acupuncture, vibration and thermal stimulation caused significant elevations of gastrin (103 +/- 11-151 +/- 16 pM, 105 +/- 8-140 +/- 12 pM and 105 +/- 14-162 +/- 4 pM) and cholecystokinin (9 +/- 0.8-15 +/- 2.8 pM, 8 +/- 0.5-10 +/- 1.5 pM and 8.0 +/- 0.5-10.5 +/- 1.5). Somatostatin was raised in response to electro-acupuncture (10 +/- 1-14 +/- 3 pM). Vagotomy and atropinization abolished the release of gastrin and CCK in response to all three stimuli. CCK levels were significantly reduced following electro-acupuncture in atropinized rats. In conclusion, gastrin and cholecystokinin release is stimulated by activation of sensory afferent, originating in skin, subcutaneous tissue as well as in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

We measured the pH of the gastric contents, as well as the gastrin- and somatostatin-like immunoreactivity in both plasma and gastric content samples, obtained from 23 infants delivered at term by elective cesarean section (ECS). In addition, we characterized the molecular forms of gastrin and somatostatin by high performance liquid chromatography. The median pH value of the gastric contents was found to be 6.78 (range 4.93-7.35). The median gastrin concentration in plasma was 54 pmol/L (range 29-190 pmol/L), which was significantly higher (p less than 0.0005) than the concentration recorded in the gastric contents, 6 pmol/L (range 0-680 pmol/L). The median somatostatin concentration in plasma was 12 pmol/L (range 4-40 pmol/L), which was significantly lower (p less than 0.0001) than the concentration found in the gastric contents, 128 pmol/L (range 15-488 pmol/L). Gastrin- and somatostatin-like immunoreactivity in both plasma and gastric contents were found to correspond to nonsulfated gastrin-34 and somatostatin-14, respectively. These data suggest that acid secretion is absent or low in infants immediately following ECS, although gastrin and somatostatin are being released into the circulation as well as into the gastric lumen. The different ratio between the concentration in plasma and gastric contents of gastrin (10:1) compared with that of somatostatin (1:10) might be related to the fact that gastrin exerts endocrine actions preferentially, whereas somatostatin is presumed to exert local paracrine effects on the gastric mucosa.

We examined whether plasma gastrin concentration increases during breast-feeding in infants. The peptide concentration was measured cross-sectionally before, during, and after breast-feeding in healthy, 3-day-old infants (n = 72). Somatostatin, a modulator of gastrin release, was also analyzed. Both peptides were measured by radioimmunoassay and were further characterized by high-performance liquid chromatography (HPLC). The (mean +/- SD) concentration of gastrin rose significantly from 63 +/- 24 pmol/L before feeding to 92 +/- 32 pmol/L (p less than 0.01) and 95 +/- 21 pmol/L (p less than 0.01), 5 and 10 min after the initiation of sucking, respectively. The gastrin concentration was 102 +/- 35 pmol/L (p less than 0.01) immediately after feeding. Plasma somatostatin concentration was unaffected by feeding. As assessed by HPLC, circulating gastrin before, during, and after feeding was found to correspond to gastrin-34, whereas circulating somatostatin was found to correspond to somatostatin-14. We conclude that in contrast to earlier studies, plasma gastrin concentration increases during and immediately after breast-feeding in infants.

The Karolinska Scales of Personality (KSP) and some dimensions of the Bergman scale reflecting social dependency and self-confidence were used in 24 individuals with functional disorders of the gastrointestinal tract. Patients showed higher scores of somatic anxiety, indirect aggression and irritability and lower scores in socialization when compared with a reference group. The levels of gastrointestinal symptoms as well as the levels of some hormones related to vagal nerve activity in this patient group have been reported in a previous publication. When the scores obtained in personality inventories were related to symptom levels, we found significant correlations with intestinal but not abdominal symptoms. Gastrin levels correlated inversely with socialization. Somatostatin levels on the other hand, correlated negatively with social dependency and positively with self-confidence in the Bergman scale. Interestingly, oxytocin levels correlated positively with social dependency and in addition with indirect aggression and verbal aggression. The correlation between hormone levels and scores of personality dimensions will be interpreted and discussed within a physiological context.

Twenty-four individuals with functional disorders of the gastrointestinal tract participated in the study. Symptoms from the upper and lower gastrointestinal tract were recorded by means of a self-administered questionnaire before, 3 months and 3 yr after participation in group therapy. Blood was sampled from the patients while they were subjected to three different provocations (a friendly greeting, a food stimulus and a stress stimulus). Ten subjects without gastrointestinal symptoms participated in an identical experiment. Gastrin, somatostatin and oxytocin levels were measured with radioimmunoassay. Both gastrin and somatostatin levels were influenced by the provocations and by the greeting and the stress stimulus in particular. In principle, the controls tended to react with a parasympathetic response pattern following the interactive stimuli, whereas the individuals with functional disorders of the gastrointestinal tract reacted with an activation of the sympathetic nervous system. Somatostatin levels were significantly higher and oxytocin levels lower in patients than in controls and gastrin levels tended to be higher in patients than in controls. Most individuals reported both gastric as well as intestinal symptoms. Gastrin levels correlated positively with total symptom level and somatostatin levels with intestinal symptoms scores reported by the patients.

This study was designed to measure plasma gastrin and somatostatin levels in infants and to simultaneously investigate the infants' metabolic status as reflected by the body weight as well as by the blood levels of FFA, D-beta-hydroxybutyrate and glucose. Healthy infants (n = 94) who were born at term were studied cross-sectionally during their first four days of life. We found that the gastrin concentration (mean +/- SD) on the first day of life was 118 +/- 37 pmol/l. Subsequently the concentration decreased and reached its lowest value on the third day; 94 +/- 27 pmol/l (P less than 0.05). On the fourth day the mean concentration increased to the same level as on the first day. There was a significant (P less than 0.01) increase in somatostatin concentrations from 18 +/- 6 pmol/l on the first day to 26 +/- 7 pmol/l on the fourth day and the concentrations were highly related (P less than 0.0001) to postnatal age. We conclude that the decrease in gastrin concentration is probably related to the low volume of breast milk ingested during the first days after delivery, and therefore to the low secretory activity of the gastrin-producing cells. The infants' catabolic condition during that time was evidenced by the reduction in body weight, the decrease in plasma glucose level and the increase in FFA and D-beta-hydroxybutyrate levels. The gastrin increase found on the fourth day reflects most likely, the change in breast milk availability which occurs with the establishment of lactation. The mechanisms controlling the release of somatostatin remains to be established.

We investigated the relationship between gastrin and somatostatin, and catecholamine concentrations in the cord blood of newborn infants. We also measured the levels of the two peptides during the first postnatal hours in the infants and furthermore characterized their molecular pattern. Twenty-two healthy infants who had been born at term were studied. Blood samples were collected from the umbilical cord and from the infants 0.5 h and 3.5 h after delivery. Peptides were measured with radioimmunoassay and further characterized by HPLC. Catecholamines were analysed by HPLC. We found that gastrin and somatostatin concentration in the umbilical cord blood was 106 +/- 40 pmol/l and 29 +/- 17 pmol/l, respectively. A significant relationship between the concentrations of somatostatin and noradrenaline in cord blood was found, (r = 0.7, n = 11, P less than 0.01). No such relation was found for gastrin. No change occurred in gastrin concentrations postnatally. Somatostatin concentration in the blood collected from the infant 0.5 h and 3.5 h after delivery was 19 +/- 11 pmol/l and 16 +/- 7 pmol/l, respectively. These concentrations were significantly lower (P less than 0.01) compared to the level measured in cord blood. Circulating gastrin was found to correspond to non-sulphated gastrin-34 and somatostatin to both somatostatin-28 and somatostatin-14. The proportion of somatostatin-28 was 30-40% and of somatostatin-14, 60-70%. We conclude that the somatostatin level, but not the gastrin level is influenced by the degree of fetal stress during labour, as evidenced by the relationship with noradrenaline. The gastrin level remained unchanged during the 3.5 h following delivery, whereas the somatostatin level decreased significantly during the same time.

Unlabelled: The role of endogenous prostaglandins as modulators of antral hormone release and gastric acid secretion was studied in the intact human stomach. The subjects (n = 9) received indomethacin prior to gastric perfusion at pH greater than 7 or less than 2 and subsequent vagal stimulation. Indomethacin was also tested against parenteral somatostatin (n = 10) and pentagastrin (n = 8). The release of somatostatin into the circulation was biphasic after vagal stimulation, and the plasma levels were inversely proportional to those of plasma gastrin. Acidification of the gastric antrum from pH greater than 7 to less than 2 increased twofold the basal plasma levels of somatostatin (p less than 0.05) and suppressed basal and vagally stimulated gastrin release (p less than 0.05) and gastric acid secretion (p less than 0.05). Indomethacin prior to acidification had little effect in the basal state. Following stimulation the release of somatostatin increased, as indicated by a twofold elevation of somatostatinlike immunoreactivity in the gastric lumen (p less than 0.05), but there was less inhibition of plasma gastrin (p less than 0.05) and gastric acid secretion (p less than 0.05) as compared to acidification alone. During alkaline gastric perfusion, indomethacin increased circulating somatostatin (p less than 0.05) levels without affecting plasma gastrin or gastric acid. Indomethacin given against intravenously infused somatostatin (0.1 microgram.kg-1.h-1) partially reversed the inhibited gastrin response to vagal stimulation without affecting somatostatin-suppressed gastric acid secretion. The effects of indomethacin against pentagastrin were marginal., In Conclusion: Gastric acidification in man stimulates plasma release of somatostatin in parallel to suppressing gastrin release and gastric acid secretion. Endogenous prostanoids participate to regulate antral hormone interactions and may have dual actions on antral somatostatin, as negative modulators of release and as mediators of somatostatin effects on the gastrin cell. It is suggested that an unrestricted release of antral somatostatin is reflected in the gastric lumen rather than in the circulation.

The objective of the present study was to measure plasma levels of cholecystokinin (CCK-8 and CCK-33,39) as well as of gastrin during the menstrual cycle and pregnancy. Cholecystokinin and gastrin levels were measured by radioimmunoassay. Before being assayed for cholecystokinin, plasma samples were submitted to HPLC which allowed separation of gastrin and cholecystokinin as well as between CCK-8 and CCK-33,39. Fasting CCK levels were 5.2 +/- 0.6 and 7.1 +/- 0.9 pM during the follicular and luteal phases of the menstrual cycle, respectively. The difference was significant (P less than 0.05). CCK levels were 8.7 +/- 1.2, 10.1 +/- 1.6 and 10.4 +/- 1.2 pM during the first, second and third trimester, respectively. CCK levels during pregnancy were significantly higher than during the menstrual cycle. The ratio between CCK-33,39 and CCK-8 appeared to increase during pregnancy. Gastrin levels remained unchanged during the menstrual cycle and pregnancy. The role of the high levels of cholecystokinin may be to stimulate the exocrine and endocrine pancreatic function during pregnancy. Furthermore, since cholecystokinin inhibits gastric emptying, it may play a role in the sickness of early pregnancy.

Somatostatin and gastrin-like immunoreactivity was measured in peripheral venous plasma at 22, 24, 02, 04 and 06 hours in 10 experiments performed on 6 healthy volunteers. In five of the experiments the subjects had been pretreated with propranolol 20-40 mg three times daily for one week. At 22 h gastrin and somatostatin levels averaged 153 and 143 pg/ml without treatment with beta-blockers and 93 and 74 with such treatment. Gastrin and somatostatin levels fell during the course of the night to approximately 10 and 60% of the 22 h value, respectively. Somatostatin levels reached their lowest value at 02 h (50%) of the 22 h value. Treatment with beta-blockers tended to decrease gastrin as well as somatostatin levels over the whole experimental period, but did not influence the gradual decline of gastrin and somatostatin levels occurring during the night or the 02 h dip in somatostatin levels. It is suggested that the nocturnal dip in somatostatin secretion is vagally mediated and that the peak in acid output occurring at this hour is due to the decreased output of gastric somatostatin. The fact that the nightly dip in somatostatin secretion coincides with the peak output of the pituitary hormones prolactin and growth hormone is discussed.

The concentration of gastrin and insulin was determined in peripheral blood of 4 lactating dogs during suckling. Suckling induced an immediate rise of gastrin and insulin levels, twofold and threefold, respectively. A peak was reached at approximately 5 min after suckling was started, and basal levels were reached again within 15-20 min. The increase in gastrin and insulin levels coincided with the let-down reflex, i.e. it occurred when the puppies started to obtain milk from their mothers. Sham feeding and feeding induce a vagally mediated increase of gastrin and insulin release in dogs. We suggest that the changes in the gastrin and insulin levels observed by us in the lactating dogs, reflect a similar vagal activation induced by suckling. Possible effects of the suckling induced release of gastrin and insulin on milk ejection and secretion are discussed.

In cats electrical vagal stimulation leads to an atropine-resistant release of gastrin. Hexamethonium on the other hand blocks the release response. These data suggest that at least one noncholinergic and one cholinergic neuron are involved in the vagal pathway innervating the gastrin producing cells. Exogenously administrated somatostatin also inhibits the vagally induced release of gastrin. Vagal stimulation decreases the levels of somatostatin in portal blood, suggesting that a release of gastric somatostatin, occurring during basal conditions, is inhibited. It is therefore possible that the vagally induced release of gastrin is in part secondary to the decreased somatostatin secretion. In contrast, electrical stimulation stimulates the release of gastrin as well as that of somatostatin into the antral lumen. However, the intraluminal release of these peptides only occurs in the presence of low antral pH. In rats, low doses of atropine (0.05 mg/kg) completely inhibits the intragastric vagally mediated release of somatostatin, which leads to an approximately 10-fold enhancement of the simultaneously occurring gastrin release. The intraluminally released somatostatin most likely derives from pH sensitive antral D cells of the open type. The vagal innervation of this population of somatostatin producing cells appears to be cholinergic. Activation of the sympathetic nervous system inhibits the vagally induced release of gastrin dependently of the prevailing antral pH. This inhibitory effect is probably exerted by a neurogenic mechanism at the ganglionic level. In contrast, basal gastrin release is enhanced by activation by the sympathoadrenal system.(ABSTRACT TRUNCATED AT 250 WORDS)

We measured the cord levels of gastrin, somatostatin and oxytocin with radioimmunoassay in plasma collected from the umbilical artery after vaginal delivery and after elective cesarean section. Maternal venous samples after the two labour modalities were also assayed for the same hormones. Fetal gastrin, somatostatin and oxytocin levels were significantly higher after vaginal delivery than after elective cesarean section. Independently of labour type, the fetal gastrin and somatostatin levels were always higher than the maternal levels. We suggest that the observed high levels of gastrin, somatostatin and oxytocin could be due to a stress-related stimulation of the oxytocin- as well as of the gastric gastrin- and somatostatin-producing cells, occurring particularly during vaginal delivery. The significant inverse correlation found between fetal pH and the recorded hormone levels is consistent with this hypothesis.

Meat in the stomach or duodenum potentiates pentagastrin-induced acid secretion in cats, presumably by a humoral mechanism. In the present study on cats, a meat meal significantly augmented the maximal acid response from a Heidenhain pouch (HP) to pentagastrin or to human synthetic gastrin I by 31 and 30%, respectively. The maximal HP acid response to pentagastrin was augmented also by peptone instilled into the stomach through a gastric fistula. Intravenous infusion of amino acids stimulated acid secretion but did not augment the maximal acid response to pentagastrin. The plasma concentrations of gastrin and somatostatin increased during infusion of pentagastrin and gastrin I and were not further altered by simultaneous feeding. The present results indicate that the mechanism for potentiation of gastrin-induced acid secretion is of physiological significance, since feeding augmented also the acid response to heptadecapeptide gastrin, the only gastrin secreted from the antrum and duodenum in cats. The potentiation of acid secretion is not dependent on the vagal excitation induced by oral feeding, since potentiation was demonstrated also by intragastric peptone instillation. The mechanism for the potentiation is not due to absorbed amino acids or a decrease of plasma somatostatin.

The object of the present work was to study the influence of antral pH, of aspirin and indomethacin, and of prostaglandins A2, E1 and E2 on the intragastric output of somatostatin and gastrin induced by electrical vagal stimulation (5 V, 2 ms, 2, 5 and 10 Hz). Experiments were performed on anaesthetized rats in which the stomach was perfused with a dextran solution (pH approximately 1.5 to approximately 6). To assess the effect of vagal stimulations on gastric acid secretion and on gastrin and somatostatin release, pH as well as somatostatin and gastrin levels was recorded in the perfusate effluent. During perfusion of the stomach with dextran solution, pH approximately 6, vagal stimulation at 10 Hz decreased perfusate pH to 1.3 and gastrin and somatostatin were released at a ratio of 2:1. Less gastrin and more somatostatin (ratio 0.1:1) was released by the same stimulation when the stomach was pre-perfused with acid solution (pH approximately 1.5), although also in these experiments the pH of the perfusate fell to 1.3. When vagal stimulations were performed after the rats had been pretreated with aspirin or indomethacin, more somatostatin than gastrin was detected in the perfusate independently of the perfusate pH. The vagally induced intraluminal release of somatostatin occurring in aspirin-treated animals was abolished by a low dose of atropine (0.05 mg kg-1) or by a simultaneous infusion of prostaglandin E1 (30 micrograms kg-1 h-1).

The aim of the present investigation was to study the effect of non-nutritive sucking on plasma levels of insulin, gastrin, and somatostatin in infants. These hormones were measured with radioimmunoassay in plasma collected from fullterm and preterm infants sucking a pacifier. In fullterm infants, sucking caused a significant increase of insulin levels from 13 +/- 10 microU/ml to 40 +/- 36 microU/ml and 21 +/- 17 microU/ml after 45 sec and 5 min respectively, from when the infants started sucking. A similar pattern was seen in preterm infants. In contrast, gastrin and somatostatin levels were not significantly affected. We suggest that sucking causes an activation of the vagal nerve, which results in the release of insulin. We also suggest that in infants, oral feeding is superior to bolus feeding, since in the latter case no vagal activation and consequently no release of hormones with anabolic properties occurs.

The objective of the present study was to investigate whether gastrointestinal hormones can be released in response to low intensity afferent activation of the sciatic nerve. Experiments were performed on anaesthetized cats in which the sciatic nerve was stimulated electrically at 3 Hz, to V and 0.2 ms. Blood samples were collected in a peripheral vein and the plasma levels of somatostatin, gastrin, glucagon, insulin and VIP-like immunoreactivity (below referred to as somatostatin, gastrin, glucagon, insulin and VIP) were recorded by radioimmunoassay. Afferent stimulation of the sciatic nerve caused immediate (approximately 15 min long) changes of the levels of all the above mentioned peptides. Somatostatin, gastrin and glucagon levels rose significantly, whereas in the case of insulin and VIP a significant relationship between the effect of sciatic nerve stimulation and basal levels was established. Thus, insulin and VIP levels decreased when basal levels were high and increased when basal levels were low. The secretion of gastrointestinal and pancreatic hormones is in part regulated by the autonomic nervous system. It is suggested that afferent stimulation of the sciatic nerve causes a reflex activation of the vagal and/or the splanchnic nerves, which in turn affects the release rate of the above-mentioned hormones. In conclusion, these data show that the release of gastrointestinal hormones can be influenced by low intensity stimulation of the sciatic nerve. The physiological trigger of these responses may be touching of the skin.

Gastrin levels, in the peripheral venous blood of conscious dogs treated with apomorphine (0.05 mg/kg IV), were analysed with a radioimmunoassay. Pretreatment (30 min) with the gastric acid inhibitors cimetidine, ranitidine (H2 receptor antagonists, 4 mg/kg and 1 mg/kg respectively) or omeprazole (H+-K+ ATPase inhibitor, 1.6 mg/kg) prolonged the elevation of gastrin levels occurring in response to an administration of apomorphine. Haloperidol (0.1 mg/kg), but not the peripheral dopamine receptor antagonist domperidone (0.2 mg/kg), abolished the enhanced gastrin response to apomorphine occurring after pretreatment with cimetidine. Cimetidine did not increase the gastrin response to apomorphine in vagotomized dogs. The results are interpreted in terms of an additive gastrin response to apomorphine (different from the short lasting initial peak previously described) which is vagally mediated and inhibited by the gastric acid.

Changes in plasma concentrations of adrenaline, noradrenaline, dopamine and gastrin in response to a standard meal were studied in 6 normal volunteers and 8 patients with chronic duodenal ulcer (DU) disease. Before the meal plasma gastrin and noradrenaline, but not adrenaline or dopamine, were higher in DU patients than in the controls. Food induced significant increments in plasma gastrin and noradrenaline concentration in both groups, whereas plasma adrenaline and dopamine levels remained unchanged. Plasma gastrin and noradrenaline concentrations were higher in DU patients than in the normal controls both during and after the meal. The results do not support the hypothesis that adrenaline is involved in the pathogenesis of duodenal ulcer disease, whereas the role of the increased plasma noradrenaline concentrations in this disease remains unclear.

The aim of the present study was to investigate how infusion of gastrin-17 and oxytocin affects plasma levels of insulin, glucagon and glucose in order to elucidate how the two hormones contribute to metabolic changes seen in situations where they are released, e.g. feeding and suckling during lactation. Thus, gastrin-17 (0.5 and 2.0 nmol kg-1 h-1) and oxytocin (0.11 and 1.1 nmol kg-1 h-1) were infused separately or simultaneously into conscious dogs. Both gastrin-17 and oxytocin induced significant, dose-dependent increases in insulin levels. An additive effect on insulin levels was obtained when gastrin-17 and oxytocin were infused simultaneously. Glucagon levels were not affected by gastrin-17 whereas infusion of 1.1 nmol kg-1 h-1 of oxytocin was followed by a significant increase. In contrast to a slight transient increase in the glucose level induced by oxytocin, infusion of gastrin-17 caused a sustained period of hypoglycaemia. Thus, infusion of gastrin-17 and oxytocin, respectively, gave rise to different ratios between circulating concentrations of insulin and glucagon reflected in different effects on the glucose level. The gastrin-induced hypoglycaemia could reflect that gastrin, via a release of insulin, promotes storing of glucose, e.g. in connection with feeding. That infusion of oxytocin caused a parallel increase in insulin and glucagon levels together with a slight increase in the glucose level could imply that oxytocin favours mobilization of glucose, e.g. during lactation.

In monogastric animals, suckling influences the secretion of gastrointestinal hormones during lactation. The aim of the present study was to investigate whether similar effects are induced by milking in cows. Experiments were performed on four cows in midlactation. Blood samples were drawn from a chronic jugular vein catheter and gastrin, and somatostatin were determined by radioimmunoassay. Milking and feeding increased plasma gastrin. Somatostatin increased at morning milking and at feeding, but it decreased at evening milking. Atropine injected subcutaneously 30 min before milking increased resting concentrations of gastrin but decreased resting concentrations of somatostatin. Feeding-induced release of gastrin remained but the milking-induced release disappeared. The milking- and feeding-induced effect on somatostatin became more marked. We suggest that milking influences gastrin and somatostatin via activation of the vagal nerves. The gastrin release caused by milking may be mediated via a cholinergic mechanism, whereas the atropine resistant effect on gastrin caused by feeding and on somatostatin caused by both milking and feeding suggest that a noncholinergic, perhaps peptidergic, transmitter may be involved.

Plasma levels of gastrinlike, somatostatinlike, and cholecystokininlike immunoreactivity were determined by radioimmunoassay in peripheral blood from 11 beagles during pregnancy and in response to suckling during lactation. Cholecystokinin was determined in pooled and in individual plasma samples after separation of cholecystokinin and gastrin by high-performance liquid chromatography. Gastrin and somatostatin levels were significantly increased during the 8-wk-long dog pregnancy; peak values were recorded in week 7 and week 4, respectively. The cholecystokinin level rose and peaked at week 3, and remained elevated. In response to suckling, maternal gastrin levels rose significantly when tested in week 1 and 3 of lactation. Somatostatin levels did not respond significantly to suckling, but basal levels were elevated in week 1 compared to week 3 of lactation. Cholecystokinin rose in response to suckling both in week 1 and 3 of lactation. We suggest that the increased levels of gastrointestinal hormones during pregnancy and lactation may serve to increase digestive and anabolic capacity.

The relation between the basal and stimulated gastric acid secretion, plasma gastrin, and the gastric microflora was examined in 45 patients with rheumatoid arthritis. Sixteen patients (36%) had basal achlorhydria, and of these, 10 (22%) had achlorhydria or hypochlorhydria after stimulation with pentagastrin. The peak acid output and acidity showed inverse correlation with the disease duration but were not associated with age or with the degree of physical disability. Hypergastrinaemia was found in nine patients (20%), of whom 6 (13%) had significant titres of parietal cell antibody. The acidity of the peak acid output showed negative correlation with plasma gastrin. It was confirmed that the gastric secretory state is a determinant of plasma gastrin levels and in addition influences the growth of micro-organisms in the gastric lumen. The type of microflora in the non-acid stomach was similar to that found in the saliva. A subgroup of eight females was identified who showed low gastric acid secretion rates, positive bacterial cultures, and atlantoaxial subluxation. Gastrin- and insulin-like immunoreactivities were found in joint fluid. The concentrations reflected their plasma levels, suggesting that the peptides are not released at the inflammatory site, but rather that they reach synovial fluid from circulating blood.

The levels of growth hormone, vasopressin, prolactin, calcitonin, gastrin, insulin, epinephrine, norepinephrine and dopamine were measured in six lactating women during breast feeding. Prolactin levels increased in response to suckling as expected. In addition, insulin levels rose two-fold. No consistent changes were observed in the levels of the other hormones. It is suggested that the suckling related insulin release is either secondary to a reflexly induced activation of the vagal nerves or to the increased circulating levels of prolactin. Furthermore, it is suggested that the insulin release in response to suckling participates in the stimulation of milk production.

Blood samples were collected in peripheral venous blood of seven lactating sows, when their piglets were suckling. In four of the experiments samples were also taken when the sows were fed a meal. Gastrin, insulin, somatostatin and VIP levels were measured by radioimmunoassay. Insulin levels increased by approximately 100% for about 10 min in response to suckling, in some experiments even before the suckling occurred, i.e. when the sows saw, heard and smelled their piglets. In four of the sows suckling caused a biphasic twofold increase in gastrin levels - one immediate peak which lasted for a few min and a second peak of longer duration (about 30-60 min), whereas gastrin levels remained unchanged in three animals. Somatostatin levels usually reflected gastrin levels in a reciprocal way. Thus, a biphasic decrease of somatostatin levels occurred in the high gastrin responders. In contrast, somatostatin levels increased in the experiments, in which gastrin levels did not change. Immediate and short-lasting (a few minutes long) increases of VIP levels were also induced by suckling. Large litters and long suckling periods appeared to be related to greater changes of the levels of all the peptides measured. Feeding influenced insulin, gastrin and somatostatin levels in the same way as did suckling from both a qualitative and a quantitative point of view. In contrast, VIP levels were not increased by feeding. The possible functional effects of the suckling-induced release of gastrointestinal hormones and possible mechanisms of their release are discussed.

Five patients with megaloblastic anemia due to deficiency of vitamin B12 and achlorhydria and six normal controls participated in the study. The patients with pernicious anemia (PA) had elevated plasma gastrin levels, as expected, and lower plasma somatostatin (SST) levels than the control patients. The amount of gastrin and SST in the antral mucosa did not differ in the two groups of patients. In the fundic mucosa, the patients with PA had increased tissue concentrations of both gastrin and SST as compared with the tissue concentrations in the controls. These findings of hormone tissue concentrations were correlated to the number of argyrophilic cells. Thus, in the antral mucosa the number of argyrophilic cells did not differ in patients with PA and in the controls. In the fundic mucosa, however, the number of argyrophilic cells was significantly elevated in patients with PA as compared with the controls.

The aim of the present study was to investigate whether plasma levels of gastrin, somatostatin, insulin, oxytocin, VIP and blood glucose levels vary during the menstrual cycle. Therefore, 19 healthy menstruating women (5 of whom were on low-dose oral contraceptives, o.c.) were blood sampled every second to third day during the menstrual cycle. Hormone levels were measured with radio-immunoassay. Gastrin, insulin, VIP and blood sugar levels remained unchanged during the menstrual cycle. Mean somatostatin levels were significantly lower in women receiving o.c. than in women without such medication (p less than 0.05). In women on o.c., somatostatin concentrations were also significantly lower during the menstrual week, than during the rest of the period (p less than 0.01), but in women without o.c., no such change occurred. Mean oxytocin levels were significantly higher in women on o.c. (p less than 0.001) and in these women, oxytocin levels recorded during the menstrual week were significantly lower than during the rest of the period (p less than 0.02). Systolic and diastolic blood pressure values were also significantly higher in women on o.c. (p less than 0.05 and p less than 0.01). In conclusion, these data show that basal plasma concentrations of gastrin, somatostatin, VIP, insulin and glucagon do not vary during the menstrual cycle. However, ingestion of low-dose oral contraceptives causes a significant decrease of somatostatin concentrations and a significant increase in oxytocin levels, suggesting that low doses of estrogens and/or gestagens may influence digestive and metabolic processes.

The postprandial secretion of insulin, gastrin and somatostatin was studied in 23 extremely obese subjects and nine normal-weight controls after a liquid test meal. Apart from a significantly higher insulin level in the obese group, no significant intergroup difference was found. The effect of weight loss on the same hormones was studied in 18 patients 6 months after gastric banding. The mean weight loss during this period was 33 +/- 2.1 (SEM) kg. There was significant decrease in postprandial insulin secretion after gastric banding, but neither gastrin nor somatostatin levels were altered.

Apomorphine (0.05 mg/kg intravenously) was given to conscious dogs, and gastrin levels were measured in peripheral venous blood with a radioimmunoassay. Apomorphine induced an increase of gastrin levels which peaked at 5 min. The peripheral dopamine D-2/DA2 receptor antagonist domperidone (0.2 mg/kg), but not halopemide (0.1-1 mg/kg) nor the D-1/DA1 receptor antagonist SCH 23,390 (0.1 mg/kg), blocked the gastrin response to apomorphine. Both domperidone and halopemide, but not SCH 23,390, blocked the apomorphine-induced vomiting. These results suggest that apomorphine increases gastrin levels by an action at D-2/DA2 receptors, which are situated outside the blood brain barrier and differ from the receptor inducing the vomiting.

Plasma levels of somatostatin like immunoreactivity (SLI), below referred to as somatostatin levels, were measured in peripheral plasma of conscious dogs. Basal somatostatin levels averaged 49 +/- 10 pM. Somatostatin as well as gastrin and insulin plasma levels were measured before and after feeding with and without prior atropinization. During the first 10 min after feeding somatostatin levels fell from 49 +/- 10 to 23 +/- 9 pM, whereas gastrin and insulin levels rose from 9 +/- 2 and 140 +/- 14 pM to 48 +/- 11 and 370 +/- 91 pM respectively. Atropine 0.01 or 0.1 mg/kg did not inhibit these responses. After the initial decrease, somatostatin level rose again and peaked at around 60 min after feeding (110 +/- 24 pM). This secondary rise was completely abolished by atropine in both doses tried. Gastrin and insulin levels remained elevated throughout the experiments with and without atropine. It is suggested that gastrin release and HCl secretion are inhibited by a tonic outflow of gastric somatostatin during basal conditions. The process of feeding induces an atropine resistant, vagally mediated decrease in somatostatin release from the gastrointestinal tract and this decreased output of somatostatin facilitates initiation of meal-related endocrine and exocrine gastric secretions.

Sick neonates often have a disturbed gastrointestinal motility. As somatostatin inhibits various gastrointestinal functions, we investigated whether or not somatostatin levels are high in sick infants. Somatostatin and gastrin levels were measured in plasma samples collected from sick and healthy neonates. Somatostatin levels were found to be significantly elevated in sick infants when compared to healthy ones, both term (91 versus 5 pM) and preterm (35 versus 5 pM). We suggest that the gastrointestinal symptoms seen in infants during illness may be related to an enhanced secretion of gastric somatostatin.

In the present study, a radioimmunoassay for oxytocin determinations is presented. In addition, we investigated whether the elevation of insulin, VIP and gastrin levels demonstrated to occur in response to suckling in lactating dogs may be induced by released oxytocin. Therefore, oxytocin was infused i.v. into conscious dogs in amounts calculated to give rise to plasma levels observed during physiological circumstances. Plasma levels of oxytocin, insulin, VIP (vasoactive intestinal polypeptide) and gastrin were measured by radioimmunoassay. When oxytocin was infused at a rate of 0.22 and 2.2 nmol kg-1 h-1, plasma oxytocin levels rose to 176 +/- 25 fmol ml-1 and to 1490 +/- 400 fmol ml-1, respectively, 10 min after the infusions were started. Plasma insulin levels rose in response to oxytocin administered at a rate of 0.22 and 2.2 nmol kg-1 h-1. A peak was recorded within 5 min of oxytocin infusion, that is, before maximal oxytocin levels were recorded, and basal levels were reached within about 20 min. The VIP levels rose slightly following infusion of oxytocin at 0.22 nmol kg-1 h-1, but a clear-cut response that lasted for 60 min was observed following infusion of oxytocin at the highest dose. In contrast, gastrin levels were not influenced by the oxytocin infusions. Suckling in dogs is followed by rapidly occurring short-lasting elevations of oxytocin levels in plasma which amount to 50-100 fmol ml-1. Since insulin and VIP were released by oxytocin when administered in amounts that give rise to plasma levels close to those levels, it is suggested that the secretion of insulin and VIP that occurs in response to suckling in lactating dogs may in part be caused by previously released oxytocin.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal gastrin and somatostatin levels have been shown to be influenced during suckling in dogs and pigs. The present study was performed to investigate whether the levels of gastrin and somatostatin are influenced by breast feeding in lactating women. Repeated blood samples were drawn in connection with nursing in 15 females and plasma levels of gastrin and somatostatin were measured by radioimmunoassay. Gastrin levels rose significantly (P = 0.01) within two minutes after onset of suckling. Somatostatin levels either decreased or increased as an effect of breast feeding. The direction of the change was correlated to the pre-suckling somatostatin levels (P less than 0.01). The somatostatin level recorded 60 min after start of breast feeding was significantly lower than basal levels (P less than 0.01) indicating a long-term inhibitory effect on somatostatin secretion. The suckling-induced effect on somatostatin levels was correlated with the amount of milk ejected (Rs - 0.52, P less than 0.05). The mechanism by which suckling influences circulating gastrin and somatostatin levels is unknown, but we suggest that suckling leads to a reflex activation of the vagal nerves, which influence the release of these hormones from the stomach. The size of the gastrointestinal tract is increased during pregnancy and lactation, illustrating that the maternal digestive capacity is adapted to the high demand for energy intake occurring during lactation. We speculate that the suckling stimulus enhances gastric functions by influencing the release of gastrin and somatostatin, which stimulate and inhibit gastric functions and growth, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The plasma concentrations of gastrin and somatostatin were measured by radioimmunoassay before and after breast feeding in healthy 4 day old infants who had been born at full term. The mean (SD) concentrations of gastrin and somatostatin before breast feeding were 120 (30) pmol/l and 35 (12) pmol/l, respectively. Breast feeding in these infants was not followed by increased concentrations of gastrin and somatostatin in peripheral blood. High preprandial peptide concentrations, as seen during the neonatal period may limit the further release of peptide after feeding.

The aim of the present investigation was to study volume, pH and the levels of gastrin- and somatostatin-like immunoreactivity in gastric aspirates obtained immediately after birth from 25 healthy infants. In addition, the same parameters were measured in amniotic fluid collected from 11 of the mothers. The median volume of the gastric contents was 4 ml (range 0-11) and median pH was 6.96 (range 2.77-9.58). Gastrin and somatostatin median concentrations were 8 pM (range 0-52) and 67 pM (range 15- greater than 1,000), respectively. The corresponding levels in amniotic fluid were 8.2 +/- 3.6 pM and 28.4 +/- 5.3 pM, median pH was 9.22 (range 8.05-9.58). There was a significant correlation between volume and pH of gastric contents. The pH of the gastric aspirate was inversely correlated with the somatostatin levels. No correlation could be demonstrated as regards levels in amniotic fluid and gastric content. Gastric content and amniotic fluid were not correlated regarding pH, gastrin and somatostatin. It is suggested that the foetus drinks about 10 ml portions of amniotic fluid which are gradually emptied from the stomach and that these drinking episodes are associated with gastric exocrine and endocrine secretion normally seen following feeding after birth.

A humoral mechanism, potentiating the maximal acid, but not the pepsin response to exogenous gastrin in cats, is activated by protein-rich food in the stomach or duodenum, but not in the jejunum. In the present study, the effect of an oral meat meal on the maximal acid response to pentagastrin was investigated in Heidenhain pouch (HP) cats, and in antrectomized HP cats with duodenal exclusion and gastrojejunostomy Rouxen-Y. Antrectomy and duodenal exclusion abolished the postprandial HP acid response, and feeding did not potentiate the acid response to pentagastrin. The finding suggests that the gastrin-potentiating mechanism in the stomach is localized in the antrum, and it cannot be demonstrated in the jejunum. The basal plasma levels of gastrin and somatostatin did not differ in antrectomized and non-antrectomized cats. Antrectomy and duodenal exclusion abolished the postprandial gastrin and somatostatin responses. The plasma somatostatin increase during pentagastrin infusion persisted after antrectomy and duodenal exclusion. It is concluded that the antrum is not mandatory for the basal plasma levels of gastrin and somatostatin, but the postprandial gastrin response is of antral origin and may release somatostatin. Pentagastrin infusion releases extra-antral somatostatin in cats.