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Biomedical subjects

T E Adrian

Publications and source records attributed to T E Adrian.

At least 253 records · Page 14Linked to original sources

Growth hormone response to feeding in term and preterm neonates.

Plasma growth hormone concentrations were measured in 248 healthy term and preterm infants. At birth growth hormone concentrations in cord blood from both term and preterm babies were approximately 100-fold higher than those in blood drawn from healthy adults. By the sixth postnatal day basal pre-feed levels had fallen in term neonates by 65% and a marked postprandial rise was apparent; preterm infants did not show this initial fall in preprandial hormone levels nor was any response to feeding seen. However a fall in preprandial concentrations accompanied by the development of postprandial surges in growth hormone occurred during the next 2 weeks so that by 24 days the postprandial rise was similar to that of term neonates on the sixth day. We conclude that although the initial postnatal changes in plasma growth hormone concentrations are different in preterm and term infants, feeding is a major stimulus to growth hormone secretion in both groups of neonates. Further work is needed to define the precise role of this hormone in neonatal metabolic adaptation.

Growth Hormone↗

Neuroendocrine responses to stimulation of the vagus nerves in bursts in conscious calves.

Effects of stimulation of the peripheral ends of the vagus nerves below the heart at 4 Hz continuously, and at 40 Hz for 1 s at 10 s intervals, have been compared in conscious calves below behavioural threshold. Neither pattern of stimulation caused any significant change in mean aortic blood pressure or heart rate but both invariably produced a substantial increase in the flow of intestinal lymph. Each form of stimulation provoked release of glucagon, insulin and pancreatic polypeptide from the pancreas and produced a small but significant rise in mean arterial plasma glucose concentration. The release of gastric inhibitory peptide- and bombesin-like molecules from the gastrointestinal tract was not affected by vagal stimulation whereas release of vasoactive intestinal peptide was observed in response to both patterns of vagal stimulation. Evidence was obtained to suggest that gastrin-like peptides are preferentially released into the bloodstream whereas cholecystokinin-like peptides are not. Vagal stimulation releases somatostatin from the gastrointestinal tract but discontinuous stimulation seems to inhibit the release of somatostatin into the general circulation. The results that have been obtained, employing this particular protocol, suggest that the pattern of the stimulus that is applied to the vagal splanchnic innervation has relatively little effect on neuroendocrine response in this species.

Animals↗

Gut hormones in acute diarrhoea.

The gut hormone response to a breakfast meal was studied in 12 subjects hospitalised for an episode of acute diarrhoea (presumed infective) who were otherwise well and in 13 healthy control subjects. Fasting blood glucose concentrations were low but basal insulin concentrations were raised. Basal concentrations of pancreatic polypeptide and both basal and postprandial responses of motilin, enteroglucagon, and vasoactive intestinal polypeptide (VIP) were also significantly greater than controls. No abnormalities in plasma concentrations of gastrin, gastric inhibitory polypeptide (GIP) or pancreatic glucagon were found. The suggested physiological actions of the raised hormones may be relevant to the pathophysiology of diarrhoea.

Acute Disease↗

Pancreatic polypeptide and calcitonin secretion from a pancreatic tumour-clinical improvement after hepatic artery embolization.

We present a case in which plasma pancreatic polypeptide and calcitonin were found to be raised in association with an islet cell tumour of the pancreas and its hepatic metastases. In this patient, no specific endocrine syndrome was found. Therapeutic hepatic artery embolization improved the general health of the patient with no change in plasma pancreatic polypeptide, but a fall in calcitonin.

Adenoma, Islet Cell↗

Effect of partial ileal bypass on the gut hormone responses to food in man.

The integrated response of the regulatory peptides of the gastrointestinal tract to a test meal was studied in six hypercholesterolaemic patients who had undergone partial ileal bypass (PIB) and compared with responses in ten age- and sex-matched controls. Plasma motilin was found to rise significantly whereas plasma pancreatic polypeptide release was impaired after PIB. Plasma cholecystokinin rose promptly in both controls and the partial ileal bypass patients, and the latter group showed marked further rises, at 60 and 120 minutes after the meal, which were significantly higher than controls. Basal and postprandial plasma gastrin, gastric inhibitory peptide, neurotensin, enteroglucagon, insulin and pancreatic glucagon were similar in the two groups.

Adult↗

Tissue localization and relative distribution of regulatory peptides in separated layers from the human bowel.

The localization and distribution of regulatory peptides was studied in separated epithelium, lamina propria, submucosa, and external muscular layer from 16 specimens of human bowel. Immunoreactive enteroglucagon, gastric inhibitory polypeptide, and neurotensin were almost confined to the epithelial fraction (97.5 +/- 2.2%, 97.5 +/- 4.2%, and 99.3 +/- 1.1% of their respective total content, mean +/- SEM) and were only localized in endocrine cells. Vasoactive intestinal polypeptide-, substance P-, and bombesinlike peptides were virtually restricted to the nonepithelial layers (99.6 +/- 0.2%, 99.6 +/- 0.2%, and 100%) and were demonstrated exclusively in nerves. A particularly rich vasoactive intestinal polypeptide- and substance P-immunoreactive nerve supply was seen in the nonepithelial mucosa, which contained the highest concentrations of these peptides, while bombesin was mainly recovered from the external muscle (87.7 +/- 2.7%). Somatostatin, measured with an antiserum highly specific for somatostatin-14, was found throughout the wall, mainly in the epithelium (39.9 +/- 5.2%) and lamina propria (29.5 +/- 5.9%), but could be immunostained only in endocrine cells.

Aged↗

Neural regulation of pancreatic polypeptide release.

To clarify the nervous system's role in the regulation of pancreatic polypeptide (PP) release, extrinsic innervation to the in situ pancreas was eliminated in five dogs. Before and 2 weeks after denervation, PP was measured during insulin hypoglycemia and ingestion of a protein meal. Exogenous insulin caused a similar marked hypoglycemia in both control and denervated dogs. Hypoglycemia caused a significant increase in plasma PP in control dogs from a baseline of 42 +/- 8 pg/ml to 86 +/- 18 pg/ml at 20 minutes (P less than 0.01). In denervated dogs plasma PP did not increase with hypoglycemia, and levels were significantly less than in the control animals at 30 and 60 minutes (P less than 0.05). With a protein meal, PP increased in the control animals from 53 +/- 12 to 116 +/- 16 pg/ml at 10 minutes (P less than 0.05), 164 +/- 22 pg/ml at 20 minutes (P less than 0.05), and 193 +/- 20 pg/ml at 60 minutes (P less than 0.01). Denervation markedly blunted this response, and PP increased only from 53 +/- 6 to 64 +/- 4 pg/ml at 10 minutes, to 83 +/- 12 pg/ml at 20 minutes, and to 91 +/- 8 pg/ml at 60 minutes. PP became significantly elevated above baseline in denervated dogs only at 60 minutes (P less than 0.05), and PP was significantly lower than in the control group at 10, 20, and 60 minutes after the meal (P less than 0.05). Immunostaining for insulin, glucagon, somatostatin, and PP showed no difference in the number and distribution of these endocrine cells in predenervation and postdenervation specimens. Adrenergic and cholinergic nerves were seen in all control specimens but, except for a few adrenergic fibers, were not seen in denervated animals. Peptidergic nerves that contained vasoactive intestinal polypeptide (VIP) were seen in all areas of the pancreas before and after denervation. This study confirms that the initial rise in PP with a protein meal is governed by vagal cholinergic pathways. Later postprandial PP secretion is controlled by an interplay between these cholinergic pathways and other uncertain influences such as hormonal or substrate changes. The pancreas has a rich intrinsic peptidergic system of VIP-containing nerves.

Animals↗

Adult cystic fibrosis: postprandial response of gut regulatory peptides.

Responses of 11 gastrointestinal regulatory peptides to a standard test meal were assessed in 10 adult patients with cystic fibrosis. The basal plasma neurotensin was significantly elevated in patients with cystic fibrosis, being 31.5 +/- 6.1 pmol/L compared with a control value of 10.3 +/- 1.5 pmol/L (p less than 0.005). Plasma neurotensin remained elevated throughout the test period. Basal plasma enteroglucagon was similarly elevated, the patients with fibrocystic disease having levels of 51.3 +/- 4.6 pmol/L compared to controls with levels of 33.2 +/- 6.7 pmol/L (p less than 0.02). There was, however, no significant difference in postprandial levels of plasma enteroglucagon. Postprandial motilin was significantly elevated in the patients with cystic fibrosis; this elevation is in contrast with previous findings in children. Release of gastric inhibitory polypeptide was impaired, while release of cholecystokinin showed no significant difference in control values, although there was a tendency for delay. There was no significant postprandial rise of pancreatic polypeptide in the patients, whose levels were grossly lower than controls. Insulin showed a delayed response. No significant differences were observed between patients and controls in levels of gastrin, pancreatic glucagon, somatostatin, or vasoactive intestinal peptide. The elevation of plasma neurotensin and enteroglucagon in the basal state may reflect an adaptive response and may be part of the improved digestive function in adults compared with children with fibrocystic disease.

Adult↗

The effect of a synthetic enkephalin analogue on postprandial gastrointestinal and pancreatic hormone secretion.

The effect of the synthetic enkephalin analogue Sandoz FK33-824 (DAMME) on gastric emptying and the postprandial secretion of upper gastrointestinal and pancreatic hormones was investigated in six healthy subjects. Gastric emptying was delayed as was the postprandial rise in glucose. There was significant blunting of insulin and gastric inhibitory polypeptide secretion, with complete abolition of the normal postprandial increases in pancreatic polypeptide and motilin. The secretion of gastrin was prolonged. These results demonstrate that pharmacological doses of opiate peptides inhibit gastric emptying and may have direct and indirect effects on gastrointestinal and pancreatic hormone secretion.

Adult↗

Pancreatic polypeptide is not involved in the regulation of the migrating motor complex in man.

The role of pancreatic polypeptide (PP) and motilin in the regulation of the migrating motor complex (MMC) was studied in normal subjects. Both plasma motilin and PP levels changed cyclically in the fasted state and were highest in the late phase II period preceding the activity front in the duodenum. A continental breakfast invariably disrupted the MMC and induced a fed pattern of motility. After the meal plasma motilin levels decreased whereas PP levels rose significantly. Infusion of pure porcine motilin during the fasted state induced an activity front and a rise in plasma PP levels. Infusion of bovine PP in doses producing plasma PP levels above the postprandial values neither induced an activity front nor prevented its occurrence. During PP infusion, however, plasma motilin levels were low, although the activity front was not inhibited. PP seems to have no clear role in the regulation of the motor component of the MMC of man. The role of motilin in the production of the activity front of the MMC is discussed.

Duodenum↗

The effect of adrenergic and cholinergic mechanisms on the secretion of pancreatic polypeptide and gastrin following hypoglycaemia in man.

The changes of plasma pancreatic polypeptide (PP) and plasma gastrin following acute insulin-induced hypoglycaemia (0 . 15 U/kg) were examined in six normal subjects, six tetraplegic subjects (preganglionic sympathectomy) and six tetraplegic subjects given atropine (combined adrenergic denervation and cholinergic blockade). Adequate hypoglycaemia was achieved in all three groups. The normal rise of plasma PP following hypoglycaemia was present in the tetraplegic group without atropine but was abolished in the tetraplegic subjects given atropine. There was no significant rise in plasma gastrin following hypoglycaemia except in the tetraplegic group given atropine. These results confirm that the secretion of PP in response to acute hypoglycaemia is mediated via cholinergic activity, while gastrin secretion appears to be inhibited in normal subjects by a vagal cholinergic mechanism.

Adult↗

Feeding and the development of enteroinsular hormone secretion in the preterm infant: effects of continuous gastric infusions of human milk compared with intermittent boluses.

Preterm infants receive gastric milk feeds as continuous infusions or intermittent boluses. It is not known whether these feeding methods have different effects on the development of digestive metabolism. We have measured plasma levels of insulin, pancreatic polypeptide (PP), gastric inhibitory polypeptide (GIP), gastrin, motilin, enteroglucagon (EG) and neurotensin (NT) in 19 preterm infants (28-34 weeks gestation) tolerating full enteral feeding from birth. 7 infants received human milk by continuous infusion, 12 infants were bolus fed. Hormones were measured in cord blood and at 6 and 13 days of age; samples were drawn preprandially in bolus fed infants. Both groups showed similar significant increases in plasma motilin, PP, NT and EG levels. At 13 days infusion fed infants had higher insulin. GIP and gastrin levels. No difference in rate of weight gain was seen in the two groups of infants. We conclude that both methods of feeding induce progressive changes in circulating enteroinsular hormone levels. However, the endocrine milieu is different in the two groups, particularly since bolus-fed infants experience marked cyclical surges in hormones after boluses of milk by 13 days of age. These differences in hormone release may affect metabolic homeostasis.

Enteral Nutrition↗

Changes in circulating gut hormones in the horse during long distance exercise.

Venous blood samples were collected before and immediately after an 80 km ride and a 42 km race. They were analysed for blood glucose and lactate, and for plasma non-esterified fatty acids, insulin, pancreatic glucagon, pancreatic polypeptide, gastrin, gastric inhibitory peptide, somatostatin and vasoactive intestinal polypeptide concentrations. The 80 km ride was associated with marked hypoglycaemia and a slight lactic acidaemia together with an increase in plasma glucagon, somatostatin, pancreatic polypeptide and vasoactive intestinal polypeptide values. The 42 km race produced hyperglycaemia and marked lactic acidaemia together with an increase in plasma glucagon, somatostatin and vasoactive intestinal polypeptide. The increase in these peptides is not related to alterations in blood glucose or the relative contributions of aerobic and anaerobic muscle metabolism. It is suggested that the changes in circulating gut peptides are part of the endocrine response to exercise and the possible physiological role of these changes is discussed.

Animals↗

Gut hormone release after intestinal resection.

To investigate the possible role of gut and pancreatic hormones in the adaptive responses to gut resection, plasma concentrations of the circulating hormones were measured, in response to a test breakfast, in patients with either small or large intestinal resection and in healthy control subjects. In 18 patients with partial ileal resection a significant threefold rise was found in basal and postprandial levels of pancreatic polypeptide, a fourfold increase in motilin, and more than a twofold increase in gastrin and enteroglucagon levels compared with healthy controls. In contrast, nine patients with colonic resection had a threefold rise in levels of pancreatic polypeptide only. One or more of these peptides may have a role in stimulating the adaptive changes found after gut resection.

Adult↗

Effect of pancreatic polypeptide on gallbladder pressure and hepatic bile secretion.

Intraluminal gallbladder pressure, measured by radiotelemetry, and bile output were monitored during infusion of porcine pancreatic polypeptide (PP) at doses of 6, 25, 100, and 400 pmol . kg-1 . h-1 in healthy conscious pigs. Plasma PP concentrations during infusion of the three lower doses, measured by radioimmunoassay, were within the range seen postprandially in these animals. Gallbladder pressure fell in a dose-related manner during PP infusion by 2.2 +/- 0.9, 8.2 +/- 0.4, 11.6 +/- 0.7, and 14.8 +/- 0.8 mmHg, respectively. In addition, a significant reduction in the bile output was observed during infusion of the two higher doses of PP. In a separate series of experiments, using cholecystectomized pigs, PP had no effect on bile output. These findings suggest that the amount of PP released postprandially may be sufficient to influence gallbladder function but not hepatic secretion of bile in the pig.

Animals↗

Pancreatic and gastrointestinal hormones in chronic pancreatitis.

Pancreatic and gut hormones have been measured in 39 patients with chronic pancreatitis, 16 of whom had severe pancreatic insufficiency. Patients with pancreatic insufficiency had significantly diminished fasting levels and postprandial rises of pancreatic polypeptide which were less than 20% of normal. Patients with chronic pancreatitis, with or without exocrine insufficiency, had two- to threefold higher plasma levels of motilin and enteroglucagon than controls. Plasma levels of insulin, pancreatic glucagon, gastric inhibitory polypeptide and gastrin were similar to normal in these patients. The pattern of response of these hormones to a test breakfast differs markedly from those seen in other gut disease states and may reflect pathophysiological mechanisms.

Adult↗

Acute rise of pancreatic polypeptide after electroconvulsive therapy.

Plasma pancreatic polypeptide concentrations rise by 320 +/- 81 per cent following administration of electroconvulsive therapy. This rise is observed in the first ten minutes despite premedication of patients with 0.6 mg atropine. Pancreatic polypeptide release is dependent on cholinergic tone and is very sensitive to atropine. The dramatic rise in pancreative polypeptide observed following electroconvulsive therapy probably results from vagal stimulation and reflects insufficient atropine premedication.

Atropine↗