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The aims of this study were to investigate if administration of oxytocin to ad libitum fed and food-restricted female rats affects weight gain, body fatness, the IGF-axis, and some vagally mediated gastrointestinal hormones, such as gastrin, cholecystokinin (CCK) and somatostatin. Ad libitum fed and food-restricted (receiving 70% of the food intake of the ad libitum fed group) female rats were injected subcutaneously, once a day, for 10 days, with saline (control) or oxytocin (1 mg kg-1 bodyweight). The animals were killed 5 days after the last injection. Oxytocin-treated food-restricted females had more body fat and lower plasma levels of IGF-I, IGFBP-1 and IGFBP-3 compared with saline-treated counterparts. Oxytocin-treated ad libitum fed rats also had lower plasma levels of IGFBP-1 but contained less body fat, compared with saline-treated counterparts. There was no effect of oxytocin treatment on body weight or weight gain in either of the feeding groups. Except for gastrin, which was lower, there was no effect of oxytocin on the gastrointestinal hormones studied. The results indicate that oxytocin treatment influences fat deposition and the IGF-axis in female rats, but that the results are dependent on the nutritional status of the animal.

Stress or noxious stimuli of various kind may induce the fight-flight response. In this situation a number of physiological and behavioural adaptations leading to defense of the organism occur. At a central level increased activity in the noradrenergic locus coeruleus (LC) and an enhanced secretion of corticotrophin-releasing factor (CRF) and vasopressin produced in the paraventricular nucleus (PVN) integrate stress response. Here the existence of an opposite psycho-physiological pattern associated with relaxation and growth and which is activated by certain types of non-noxious stimuli and integrated by oxytocin is proposed. In support of this, administration of oxytocin to male and female rats gives rise to effects of antistress nature in particular after repeated administration. Thus a five day treatment period with oxytocin 1 mg/kg s.c. or 1 micro g/kg i.c.v gives rise to sedation, lowering of blood pressure, increased withdrawal latency in the tail flick test and also a decrease of corticosterone levels and a rise of certain vagally controlled hormones. Weight gain is also increased under certain conditions. These effects persist several weeks after administration of oxytocin and cannot be reversed by oxytocin antagonists when established, suggesting that secondary mechanisms have been activated. Naloxone temporarily reverses the increased withdrawal of the tail flick test suggesting that opioid mechanisms have been activated to cause this particular effect. In contrast the sedative and blood pressure lowering effect seems to be induced by an enhanced activity in central alpha 2 receptors. Oxytocin levels increase in blood and CSF after various kinds of non-noxious sensory stimulation such as touch, light pressure and warm temperature in both female and male rats. It is suggested that other types of non-noxious stimuli as well may increase oxytocin release. If so, a release of oxytocin could be responsible for not only the antistress effects occurring during lactation but also why relationships, social contact and networks may have health promoting effects in particular by preventing cardiovascular disease.

The mechanisms that regulate mammary blood flow during lactation are not fully understood. In the present study laser Doppler flowmetry (LDF) was used to measure blood flow in the cutaneous microvessels of the mammary gland of lactating rats. The effects of suckling on blood flow were examined, as were those of local injection of oxytocin (0.5-5 mU) and the vasoactive peptides calcitonin gene-related peptide (CGRP; 0.1-10 pmol), vasoactive intestinal polypeptide (VIP; 0.4-20 pmol) and neuropeptide Y (NPY; 1-40 pmol). Blood flow responses to suckling varied depending on how much time had lapsed since the previous suckling. In rats with milk in the gland, suckling caused an initial increase in blood flow. In connection with milk let-down, the blood flow decreased, but was followed by a second increase. In recently suckled rats with no milk in the gland the increase in blood flow corresponded to the number of pups suckling. Oxytocin injections also had varying effects on mammary blood flow depending on how recently suckling had taken place. In non-suckled rats with milk in the gland, oxytocin injections caused a rise in blood flow that was interrupted by a fall during milk ejection. In recently suckled rats, all doses of oxytocin caused an increase in blood flow of similar magnitude. However, the effect of the higher doses had a longer duration. CGRP and VIP injections caused a dose-dependent increase in mammary blood flow regardless of when suckling last occurred. NPY injections caused a dose-dependent decrease in blood flow.

The aim of this study was to investigate the role of vagal nerve activity for the release of oxytocin, prolactin and gastrointestinal (GI) hormones during suckling as well as for the secretion of milk in lactating rats. We have therefore performed experiments on vagotomized lactating rats. The animals were decapitated and trunk blood was collected from nonsuckling rats and from suckling rats in connection with milk ejection. Oxytocin, prolactin, vasoactive intestinal polypeptide (VIP), somatostatin, insulin, glucagon and glucose levels in plasma were measured by RIA-technique. In addition, maternal weight as well as the weight of the litters were recorded 7 d after vagotomy. As expected, oxytocin and prolactin levels rose in response to suckling in sham-operated controls. In vagotomized animals the suckling-induced increase of oxytocin was blocked and prolactin levels were significantly decreased. VIP levels in plasma increased following suckling in sham-operated animals and failed to respond after vagotomy. In contrast, somatostatin levels that rose significantly in sham-operated rats were even more significantly raised in vagotomized animals. In addition, insulin but not glucagon levels were increased by suckling. The insulin response, however, persisted after vagotomy. Interestingly, suckling was followed by a lowering of blood-glucose levels in vagotomized, but not in sham-operated animals. The vagotomized rats ate as much and increased in weight as sham-operated rats during the 7 d of vagotomy. The litters of vagotomized rats, however, gained significantly less weight in comparison with control litters. In conclusion, this study shows that vagal nerve activity is of importance for the release of oxytocin, prolactin, vasoactive intestinal polypeptide and somatostatin during suckling.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to investigate whether corticotropin-releasing factor influences the plasma levels of somatostatin, gastrin or cholecystokinin when administered intracerebroventricularly to rats, and if such an effect could be vagally mediated, and dependent on the animals feeding states. Anaesthetized, freely fed rats were given 5 microliters intracerebroventricular injections of corticotropin-releasing factor in four doses; 10 pmol-1.28 nmol. Immediately following death, trunk blood was collected for subsequent peptide analysis with radioimmunoassay (RIA). The three higher doses of corticotropin-releasing factor elevated the plasma levels of somatostatin (P < 0.01) after 20 min but left the plasma levels of gastrin and cholecystokinin unchanged. Intraperitoneal injections of 60 and 320 pmol of corticotropin-releasing factor did not influence the somatostatin levels. Further, intracerebroventricular injections of 60 pmol of corticotropin-releasing factor produced a peak increase in somatostatin after 20 min (P < 0.01). After 60 min the somatostatin levels were still increased (P < 0.05). Gastrin and cholecystokinin remained unaltered at these time-points. Intracerebroventricular administration of 10 nmol of alpha-helical corticotropin-releasing factor 9-41 attenuated the basal levels of somatostatin and blocked the corticotropin-releasing factor-induced rise in somatostatin. Bilateral truncal vagotomy, as well as pretreatment with atropine (0.05 mg kg-1, subcutaneously) abolished the effects of corticotropin-releasing factor on somatostatin. In animals which were food-deprived for 24 h, corticotropin-releasing factor did not influence somatostatin, gastrin or cholecystokinin. Pretreatment with cholecystokinin did not potentiate corticotropin-releasing factor-induced somatostatin release in food-deprived rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The objective of the present study was to investigate whether oxytocinergic mechanisms may contribute to the antinociceptive effect of non-noxious, sensory stimulation. To test this hypothesis, oxytocin levels in plasma and cerebrospinal fluid (CSF) were measured in control rats as well as in rats exposed for 30 min to electro-acupuncture (2 Hz), thermal stimulation (40 degrees C) or vibration (100 Hz). All modes of stimulation induced significant elevations of oxytocin levels in plasma and/or in CSF, 30 or 90 min after the end of stimulation. Secondly, the antinociceptive effects of these treatments were investigated in the tail-flick test with and without prior administration of the oxytocin antagonist 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin (1 mg kg-1 i.p.). All three modes of stimulation caused a significant delay of the tail-flick latency to the same degree as that caused by injection of oxytocin 1 mg kg-1 i.p. (electro-acupuncture P < 0.01, thermal stimulation and vibration P < 0.05). In all cases, the delay was reversed by administration of the oxytocin antagonist (1 mg kg-1 i.p.). These findings suggest that analgesic effects induced by non-noxious sensory stimulation may, in part, be mediated through activation of oxytocinergic mechanisms.

The effects of 24 h of fasting and refeeding on the release of oxytocin, prolactin, insulin and LH in three lactating sows were investigated. The sows were starved, but supplied with water ad libitum, from 09.00 h on day 27 of lactation until 15.00 h on day 28 of lactation, when they were refed. Blood samples were collected continuously, using an automatic collection system, at a rate of 1 ml min-1 from 09.00 to 21.00 h on day 28 (P1 = 6 h period after the 24 h fast, P2 = 6 h period after refeeding). For both P1 and P2 the mean number of nursings was 7.0 +/- 1.0. Plasma insulin and glucose decreased to very low levels during fasting and increased (P < 0.001) after refeeding (insulin, 2.5 +/- 0.7 vs. 28.9 +/- 0.7 mU l-1; glucose, 2.6 +/- 0.3 vs. 6.4 +/- 0.3 mmol l-1). Following fasting, levels of prolactin were low (2.8 +/- 0.1 micrograms l-1), and sucking did not induce significant release of prolactin. However, prolactin increased rapidly after refeeding (5.4 +/- 0.1 micrograms l-1, P < 0.001). Neither the 24 h fast nor refeeding had a marked effect on basal levels of oxytocin, the percentage of sucklings with an oxytocin peak or the size of oxytocin peak. LH release (average and basal levels and number of pulses/6 h) during fasting was similar to that measured after refeeding. Plasma CCK increased significantly after feeding. The results indicate that the release of prolactin is also regulated by feed intake.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

The aim of the present study was to investigate how the sympathetic nervous system affects the vagally induced intragastric release of somatostatin and gastrin. Experiments were performed on anaesthetized rats in which the stomach was perfused with a dextrane solution (pH approximately 5.9) or dextrane buffer (pH 7.4). pH as well as gastrin and somatostatin levels were measured in the gastric perfusate when it had passed the stomach. Vagal stimulation caused a decrease in perfusate pH and an increase of the intraluminal output of gastrin and somatostatin when the stomach was perfused with the dextrane solution pH 5.9. Pretreatment with phentolamine (1 mg kg-1) significantly increased and pretreatment with clonidine (60 micrograms kg-1 h-1) significantly decreased somatostatin release caused by vagal stimulation, whereas gastrin levels remained largely unchanged. The effect of clonidine persisted in rats pretreated with indomethacin (5 mg kg-1), which per se potentiates the vagally induced luminal somatostatin release. When the stomach was perfused with the dextrane buffer pH 7.4, basal gastrin levels were significantly higher than during perfusion with the solution pH 5.9, whereas somatostatin levels remained unchanged. Neither somatostatin nor gastrin levels increased following vagal stimulation during gastric perfusion with the dextrane buffer pH 7.4. However, following pretreatment with phentolamine somatostatin levels increased during these conditions.

Oxytocin has been shown to influence insulin, glucagon and blood glucose levels in various experimental situations. The present study was performed in order to obtain support for a possible interaction of glucose and oxytocin under physiological conditions. We therefore studied whether or not short-term food deprivation (24 hours) affects basal oxytocin levels in male, female and lactating rats, since this is a situation when glucose is mobilized to prevent hypoglycaemia. Secondly, we studied whether oxytocin levels rise in a situation when blood glucose levels fall, i.e. following i.p. injection of insulin (20 U kg-1). In order to explore the role of oxytocin more directly, we investigated whether i.p. injection of the oxytocin antagonist 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin affects blood glucose levels. Plasma levels of oxytocin, insulin and glucagon were measured with radioimmunoassay in samples obtained after decapitation. We found that oxytocin levels were significantly increased following short-term food deprivation in lactating rats. We also found that insulin-induced hypoglycaemia could elevate plasma levels of oxytocin in female and male rats. In addition, administration of an oxytocin antagonist cause a small, but significant decrease in blood glucose levels after 30 min. These data imply that oxytocin may be one of several factors that take part in the control of blood glucose regulation.

The effect of total weaning (all piglets were weaned at 35 days of lactation) and fractionated weaning (the heavier half of the litter was weaned on day 33 of lactation and the remainder 2 days later) on plasma levels of prolactin, oxytocin, insulin, glucagon, glucose, gastrin and somatostatin in primiparous sows was studied. Twelve crossbred sows were grouped into six pairs according to farrowing data and litter size. The litter of one sow in each pair was weaned in two stages (treatment), and the other was conventionally weaned (control). Blood samples were collected via a permanent jugular vein catheter every 3 hours from 9 a.m. to 9 p.m. from day 31 of lactation until the third day of final weaning. In response to total weaning (studied in the six control sows), plasma prolactin, glucagon and gastrin decreased significantly, whereas plasma insulin and somatostatin significantly increased. Basal concentrations of plasma oxytocin and glucose remained unchanged after weaning. Fractionated weaning did not result in any significant differences in the hormonal and glucose levels as compared with the total weaning. The possible role of prolactin in modulating insulin, glucagon and glucose concentrations as well as the possibility that oxytocin affects gastrin and somatostatin levels following weaning are discussed.

The effects on the urinary bladder and urethra of pelvic and hypogastric nerve stimulation and their relation to vasoactive intestinal polypeptides (VIP) were investigated in the anaesthetized dog. Both pelvic and hypogastric nerve stimulation elicited a twofold increase in urinary bladder blood flow and a clear-cut increase in bladder venous effluent VIP concentration. Hypogastric nerve stimulation induced an initial, partly alpha-adrenergic and partly non-adrenergic, non-cholinergic, contraction of the urinary bladder followed by a relaxation. The urethra response was a maintained alpha-adrenergic contraction. Pelvic nerve stimulation elicited a bladder contraction with an initial non-cholinergic peak, whereafter the bladder pressure was maintained at a lower level, an effect which was mainly cholinergic in origin. The urethral response was an initial non-adrenergic, non-cholinergic contraction followed by a maintained cholinergic contractile response. Afferent pelvic nerve stimulation led to an efferent activity that seemed to be a combination of activity in pelvic and hypogastric pathways to the urinary bladder and the urethra. VIP (10 nmol) injected i.v. induced a relaxation of the urinary bladder and the urethra, together with a fall in systemic blood pressure. However, despite high plasma concentrations, no vasodilation was elicited in the urinary bladder. Thus, the main target for the VIP release during pelvic and hypogastric nerve stimulation is probably not the bladder vasculature, but instead perhaps the bladder smooth muscle proper.

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.

Biopsies from various peripheral nerves were collected from living cats. The biopsies were extracted with acid ethanol and the insulin-like immunoreactivity (ILI) content of the extracts determined with radioimmunoassay. The vagal, sciatic and radial nerves contained on the average 90, 3 and 28 ng of ILI per gram nerve tissue (wet weight), respectively. In the sympathetic trunc no ILI was found. In order to partly purify and characterize the nerve ILI extracts these were run on an HPLC system. the ILI coeluted with standard bovine insulin. The same amounts of ILI were found in the nerve extracts whether run on the HPLC system or not. It can be concluded that all of the immunoreactive material of the nerve extracts corresponds to insulin or to a peptide very similar to insulin. In two cats the radial and sciatic nerves were ligated for 24 h. Two to ten times more ILI occurred in biopsies taken proximal to the site of ligation than in those from corresponding distal biopsies, indicating that the insulin-like material is transported distally within the nerves. ILI was found in extracts from vagal nerves taken from 3 days old human autopsy material. Also this human ILI coeluted with the bovine insulin standard in the HPLC system.

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 changes in insulin, glucagon and plasma glucose levels in response to suckling in lactating dogs. Blood samples were drawn from a peripheral vein during suckling in weeks 1 and 3 of lactation in 10 lactating beagles. Insulin- and glucagon-like immunoreactivity (below referred to as insulin and glucagon) were determined by radio-immunoassay, and plasma glucose levels by the glucose oxidase method. Insulin and glucagon levels rose following onset of suckling. However, only the rises recorded in week 3 of lactation were statistically significant. Plasma glucose levels were not affected. The mechanism by which suckling influences the levels of insulin and glucagon is not known. However, the release of both hormones is under vagal control and it is possible that touching of the teats reflexly elicits a vagally mediated release of these hormones. Alternatively, since oxytocin stimulates the secretion of insulin and glucagon, the effects might be secondary to the oxytocin released by suckling. The physiological function of the suckling-related release of insulin may be to stimulate milk production. Furthermore, since glucagon is also released, each suckling period may be accompanied by a transfer of glucose to the mammary glands from other maternal stores.

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.

The effect of weaning on plasma levels of insulin and glucagon as well as on plasma glucose levels was studied in sows after final weaning (all the piglets removed in week 5 of lactation) and fractionated weaning (7 out of 12 piglets removed in week 3 of lactation). Insulin levels rose from 24 +/- 6 to 106 +/- 22 microU ml-1 4 days after final weaning and from 11 +/- 1 to 128 +/- 20 microU ml-1 7 days after fractionated weaning. Glucagon levels fell from 60 +/- 20 and 42 +/- 8 to 35 +/- 10 and 24 +/- 5 pm in the two groups, respectively. Plasma glucose levels increased from 4.5 +/- 0.5 to 7.2 +/- 1.2 mM after fractionated weaning and remained unchanged after final weaning. One possible mechanism that can explain this pronounced insulin increase and decrease of glucagon is the elevation of plasma glucose, since milk is no longer emptied from the mammary gland and since insulin resistance occurs after weaning in rats. Another possible explanation could be a decreased number of insulin receptors in the mammary gland, since prolactin which is known to increase insulin receptors is decreased in weaned rats.

Recent evidence suggests a regulatory role in the nervous system for somatomedins. The present study, using a somatomedin radioreceptorassay which primarily detects insulin-like growth factors 1 and 2, shows that somatomedins are widely distributed throughout the nervous system of the cat. Whilst somatomedins were present in all CNS regions, the highest concentration occurred in the hypothalamus followed by cerebral cortex. In the spinal cord, the dorsal roots contained twice the concentration found in the ventral roots. Activity was also present in the sympathetic ganglia, vagus nerve and sciatic nerves. Following electrical stimulation of the brachial and sciatic nerves somatomedins were released into perfusates from extirpated cut limbs. These findings suggest that somatomedins may be neuroregulatory hormones.

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.

This study was performed in order to investigate whether activation of sensory fibres within the sciatic and vagal nerves might influence the release of oxytocin. In anaesthetized rats the sciatic and vagal nerves were stimulated electrically in an afferent direction with a variety of stimuli. Rats were also stroked on their backs or nociception was inflicted by pinching a foot. Plasma oxytocin levels were measured with a highly sensitive radioimmunoassay in samples drawn from the carotid artery. Afferent electrical stimulations of both sciatic and vagal nerves at 5 V, 0.2-2 ms and 3-10 Hz caused immediate significant elevations of oxytocin levels. Thus, basal levels increased by 30-184%. Furthermore, in response to touch and nociceptive stimuli, oxytocin levels rose by 181% and 206%, respectively. These data indicate that oxytocin can be released by stimulation of peripheral nerves originating in the skin and/or muscle and in the gastrointestinal tract and thus these organs may be involved in the control of oxytocin secretion.

The vascular system of extirpated cat legs was perfused with Tyrode's solution and insulin-like immunoreactivity (ILI) levels were determined in the perfusate with radioimmunoassay. During unstimulated conditions perfusate levels of ILI were almost undetectable. However, in response to electrical stimulation of the sciatic or brachial nerves (within a wide range of stimuli 5-40 V, 2-20 Hz and 0.2-40 ms) 1-20 ng of ILI was recorded in the perfusate. Blockers of cholinergic and adrenergic transmissions added to the perfusate did not influence the output of the ILI induced by nerve stimulation. Furthermore, after administration of acetylcholine (ACh) (0.1 and 10 micrograms kg-1), oxytocin (0.5 and 5 IU kg-1), glibenclamide (25 and 100 micrograms kg-1) and bombesin (100 and 500 micrograms kg-1) to the cat leg preparation, ILI appeared in the perfusate in amounts similar to those induced by electrical stimulation of the nerves. When subjected to high-performance liquid chromatography (HPLC) the insulin-like peptide detected in the cat leg perfusate following nervous stimulation, or administration of oxytocin and glibenclamide, co-eluted with a bovine insulin standard. We have previously shown that some peripheral nerves of the cat, such as the sciatic, brachial and vagal nerves, contain an insulin-like peptide with HPLC characteristics similar to the bovine insulin standard. It is therefore possible that the insulin-like peptide released from the isolated cat leg preparation by the above-mentioned stimuli derives from this nervous pool of insulin. Alternatively, the insulin-like peptide emanates from the striatal muscles innervated by the sciatic and brachial nerves, since also muscles have been shown to contain an insulin-like peptide.

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.

Peripheral nerves of the cat such as the vagal and the sciatic nerves have been shown to contain a peptide with insulin-like properties. The aim of the present study was to investigate whether insulin-like immunoreactivity (ILI) can be demonstrated in human nervous tissue collected from autopsy material. Biopsies were taken in connection with autopsy from various peripheral nerves and their content of ILI was investigated. ILI in amounts up to about 12 ng g-1 was found in about 30% of all biopsies taken from peripheral nerves. The ILI coeluted with a bovine insulin standard in an HPLC system indicating that it corresponds to a peptide identical with or similar to pancreatic insulin. Autopsy specimens taken from the sciatic nerve of individuals with diabetes type II or from individuals without established diabetes contained similar amounts of ILI.

The objective of the present study was to investigate whether oxytocin is released in response to feeding in analogy to the response induced by suckling. Therefore, repeated plasma samples were drawn from dogs and pigs during feeding and suckling and oxytocin levels were determined by radioimmunoassay. As expected suckling gave rise to immediate and short-lasting increases of oxytocin levels in both species. More surprisingly, feeding in female and male dogs as well as in lactating sows was accompanied by a similar-sized rise of oxytocin levels. The oxytocin peak sometimes occurred before the actual period of suckling or feeding, suggesting that the output of oxytocin had been conditioned to visual, olfactory or auditory stimuli associated with both types of situations. It is well known that oxytocin is released in lactating animals in response to touching of the teats. It is possible that also the presence of food in the gastro-intestinal tract activates neurogenic mechanisms which stimulates the release of oxytocin. Since oxytocin causes a release of insulin and VIP (vasoactive intestinal polypeptide), peptides which appear in the circulation following both suckling and feeding, it is suggested that oxytocin may be involved in the control of the suckling- and feeding-related output of these peptides.

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.

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)

Twenty-one pregnant women with nasal congestion, verified by rhinomanometry, did not differ significantly from 8 pregnant women without nasal congestion regarding the serum levels of the hormones oestradiol, progesterone and VIP. The congested group had a significantly lower serum level of oxytocin than the reference group. There were no differences in the symptoms urinary incontinence, constipation, and heartburn between the groups. The pathophysiology of nasal congestion during pregnancy is still veiled in obscurity.

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.

Oxytocin is known to increase plasma levels of insulin, glucagon and glucose in dogs. Plasma levels of vasopressin rise during stressful conditions. Since vasopressin counteracts several oxytocin-induced effects, it was decided to study how vasopressin influences the oxytocin-induced elevation of plasma levels of insulin, glucagon and glucose. Therefore oxytocin at 0.11 (which gives rise to physiological plasma concentrations) was infused i.v. for 10 min into fasted, conscious dogs either alone or in combination with 0.033 or 0.17 nmol kg-1 h-1 of L-vasopressin. Accordingly, 1.1 nmol kg-1 h-1 of oxytocin was infused alone or in combination with 0.67 or 1.7 nmol kg-1 h-1 of L-vasopressin. Repeated blood samples were drawn during and after the infusions and insulin and glucagon levels were determined by radioimmunoassay. Plasma levels of insulin increased three- and six-fold in response to 0.11 and 1.1 nmol kg-1 h-1 of oxytocin, respectively, and the elevations were inhibited by L-vasopressin. Slight (1.5-fold) increases in plasma levels of glucagon were observed following 0.11 and 1.1 nmol kg-1 h-1 of oxytocin, although the effect was significant only after the latter dose. Concomitant infusion with L-vasopressin did not markedly influence the effect caused by oxytocin. Small, insignificant increases in blood glucose levels were induced by both doses of oxytocin. These effects were not affected by concomitant infusions of L-vasopressin. The insulin levels rose before glucose levels suggesting that oxytocin stimulates the release of insulin without a previous rise in glucose levels. In conclusion, it has been shown that vasopressin, in amounts which give rise to physiological plasma concentrations, inhibits oxytocin-induced effects on insulin levels, and that oxytocin stimulates the release of insulin via a mechanism which is independent of elevations in blood glucose levels.