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Biomedical subjects

K D Buchanan

Publications and source records attributed to K D Buchanan.

At least 217 records · Page 12Linked to original sources

Role of neural influences in the release of gastrin, glucagon, and secretin during hypoglycaemia in man.

Both vagal and sympathetic innervation been have described as influencing hormone release from the gastrointestinal tract and pancreas. The role of neural influences on the release of gastrin, glucagon, and secretin has been studied using the potent autonomic nerve stimulus of hypoglycaemia. Healthy subjects were each rendered hypoglycaemic by insulin 0.2 units/kg on three occasions: after atropine 20 microgram/kg: after propranolol 160 mg orally, and without prior drug administration. Adequate beta-blockade was confirmed by observation of the pusle rate response to a standard exercise at the end of the experiment, and by measurements of plasma propranolol levels. Hypoglycaemia failed to produce a rise in plasma gastrin under either propranolol or control conditions but a significant rise was noted with prior atropinisation. The glucagon response to hypoglycaemia, when measured with either the C- or N-terminal reactive antibodies, was found not to be influenced to any significant extent by either beta-blockade or atropinisation. No alteration in plasma secretin levels was noted during hypoglycaemia. It therefore appears that neural influences are relatively unimportant in the release of gastrin, glucagon, and secretin in man.

Adult↗

Gastric emptying of ingested acid and its effects on plasma gastrin and secretin in duodenal ulcer subjects.

Abnormal acid production or handling is thought to be involved in duodenal ulceration. Gastric emptying of 25 mmol hydrochloric acid (250 ml 0.1 M solution) was studied by using an isotopic method in control and ulcer subjects. Plasma gastrin and secretin levels were simultaneously measured. Gastric emptying was significantly faster in ulcer subjects using several parameters. Plasma gastrin levels were suppressed in both groups, with equivocal differences between them. Mean plasma secretin levels showed no significant elevation in controls and at only one point in ulcer subjects. Mean elevation in plasma secretin levels during intermediate phase of gastric emptying (T30-70) correlated with rate of acid loss from stomach in both groups. Regression lines were significantly different in position, however, and indicated a higher threshold for secretin release in ulcer subjects. The significance of this in the pathogenesis of duodenal ulcer is discussed.

Adult↗

Elevations of gastrointestinal hormones in chronic renal failure.

Fasting levels of 5 gut hormones were studied in 30 patients with advanced uraemia (CRF), 40 undergoing regular dialysis (RD) and 555 renal transplant patients (RT). Mean values of gastrin and total glucagon were markedly elevated in CRF and RD patients compared with 20 normal subjects; there were lesser elevations in pancreatic glucagon, insulin and vasoactive intestinal peptide (VIP). Secretin levels were unchanged. In RT patients, fasting levels of VIP and pancreatic glucagon had returned to normal, while levels of gastrin, total glucagon and insulin remained slightly elevated compared with controls. Food stimulated hormone levels were measured in 18 RD patients and compared with 18 controls. After eating, RD patients failed to show the late increase in total glucagon, or the suppression of VIP and secretin seen in normal subjects; the pattern of gastrin and insulin response was similar to controls, but after the initial increase plasma levels in RD patients tended to show a slower decline. Thus involvement of the gastrointestinal tract in uraemia is associated with functional disturbance of the endocrine system of the gut.

Gastrins↗

Cimetidine for duodenal ulceration in patients undergoing haemodialysis.

Peptic ulcer is a common problem in advanced renal failure, but most drugs for ulcers are hazardous in this condition. In a small open study cimetidine was given to nine patients with acid hypersecretion and endoscopically diagnosed duodenal ulceration who were undergoing haemodialysis. The patients obtained good pain relief and suffered no serious side effects. Both basal and stimulated acid output fell considerably and the plasma gastrin response to food increased during treatment. Two patients with recurrent vomiting during haemodialysis had a striking response to cimetidine, which suggested that such vomiting may be acid-mediated in some patients. These preliminary results suggest that cimetidine may prove to be an advance in the management of peptic ulcer in uraemic patients.

Adolescent↗

Insulin and glucagon response to arginine infusion in cystic fibrosis.

The glucagon and insulin responses to intravenous arginine were studied in 17 children with cystic fibrosis and in 9 control children. It was found that the overall secretion of insulin was diminished; however, four of the CF children did have a normal output. The glucagon responses did not parallel those of insulin. The glucagon output varied in the CF children--seven had normal, four excessively high and six low output. Three of the four children with extremely high output had more severe disease and were below the third centile on the weight chart. These four had a fasting hypoglycaemia and also a very low glucose and insulin response. We have confirmed diminished insulin secretion in cystic fibrosis, but diminished glucagon secretion was only noted when some insulin secretion was preserved. The high levels of glucagon seen in the most insulin deficient subjects may be derived from extrapancreatic sources, or may be associated with 'stress' reaction in these patients who also had most severe pulmonary involvement. The data would be consistent with diminished glucagon and insulin secretion from the pancreas but as the disease progresses an excessive secretion of extra pancreatic glucagon results.

Arginine↗

Role of gastrointestinal hormones in the response to massive resection of the small bowel.

Hypersecretion of gastric acid and accelerated intestinal transit are largely unexplained consequences of massive resection of the small bowel; several postulated humoral mechanisms remain unsubstantiated. The purpose of the study was to investigate the effects of 75% resection of the distal small bowel in dogs on circulating levels of a range of gastrointestinal hormones. Basal and meal-stimulated concentrations of insulin, secretin, gastrin, pancreatic glucagon, and total glucagon-like immunoreactivity (GLI) were measured by radioimmunoassay techniques. After resection, significant depletions of basal and stimulated total GLI (p less than 0.05 -- p less than 0.001) and a significant rise of stimulated gastrin (p less than 0.05) were discovered. These hormonal alterations may produce an important imbalance of humoral influences on gastrointestinal function. It is suggested that these changes may hold a key to the aetiology of the complications of massive resection of the small bowel.

Animals↗

Secretin: high plasma levels in diabetes mellitus.

Plasma immunoreactive secretin levels were measured in 22 newly diagnosed non-ketotic, maturity-onset diabetics and 10 healthy control subjects during 50 gram oral glucose tolerance test (OGTT). The test was repeated in the diabetic group after 6 months' dietary treatment. At diagnosis the fasting secretin levels in the diabetics were higher than in control subjects but fell within the normal range following dietary treatment. In the diabetics there was a significant positive correlation between the fasting glucose and fasting secretin levels at the time of diagnosis. Suppression of secretin levels occurred during the OGTT, both in diabetic and control subjects.

Diabetes Mellitus↗

Treatment of peptic ulcer in renal failure.

The occurrence and pathophysiology of peptic ulcer was studied in 117 uraemic patients. Ulcer disease was unusually frequent, and the highest incidence was found in patients on regular dialysis (48%). Factors implicated were hyperacidity, hypergastrinaemia, and the effect of dialysis itself. We found that the occurrence of gastrointestinal bleeding was lower post-transplant (7%), than pre-transplant (15%), and that bleeding in renal transplant patients was due more commonly to erosive gastritis than peptic ulcer. Cimetidene was given to 9 regular dialysis patients with peptic ulcer. Symptomatic relief and significant reduction of acid secretion was demonstrated, and no major side effects occured. There is a logical basis for conservative treatment of uncomplicated peptic ulcer in the dialysis patient, and further evaluation of cimetidene is indicated.

Cimetidine↗

High circulating levels of glucagon and gastrin in anephric subjects.

Six nephrectomised patients undergoing chronic haemo-dialysis and six patients who have had renal transplantation were studied in comparison with a control group of healthy subjects. Their glucose, insulin, glucagon and gastrin levels were measured during a 50g oral glucose tolerance test which, in the dialysis group, was carried out just prior to a dialysis period. In this group fasting blood samples were obtained also on the morning immediately following dialysis. Glucagon levels were high in the dialysis group and gastrin levels were raised in both the dialysis and transplant groups. These abnormalities may be related to some of the clinical features of renal failure.

Adult↗

Triglyceride metabolism in acute starvation: the role of secretin and glucagon.

Plasma lipid and hormone levels have been measured during 72 hours total starvation in nine healthy subjects, to assess the relative importance of hormones and substrates in human triglyceride metabolism. Plasma free fatty acid and glycerol concentrations rose steadily on each day of starvation. Plasma triglyceride concentrations rose on the second and third days, from a control level of 649 +/- 67 mg/1 to a maximum of 1001 +/- 66 mg/1. Plasma cholesterol concentrations remained unchanged while glucose concentrations fell and insulin did not change. Plasma glucagon (C-GLI) levels doubled while secretin levels, reported previously, rose threefold. It is suggested that during acute starvation the rise in triglyceride concentration results from the increased availability of free fatty acids, and that elevated secretin and glucagon levels enhance lipolysis and hence provide substrates for triglyceride synthesis.

Adult↗

Avoidance of strongly chaotropic eluents for immunoaffinity chromatography by chemical modification of immobilized ligand.

The need for chaotropic eluents in immunoaffinity chromatography is a consequence of the high affinities of antibodies towards their antigens. This affinity is decreased and elution of antiglucagon antibodies from a column of immobilized glucagon can be achieved under mild conditions when the steric complementarity to the antibody binding site is perturbed by selective chemical modification of the hormone. The effects of reaction with 2-hydroxy-5-nitrobenzyl bromide, tetranitromethane and hydrogen peroxide have been studied. Conversely, treatment of immobilized antibodies with 2-hydroxy-5-nitrobenzyl bromide facilitates the elution of glucagon during immunoaffinity chromatography. The general implications of these results are discussed.

Animals↗

Secretin and insulin: response to intraduodenal acid.

Immunoreactive secretin (IRS) and immunoreactive insulin (IRI) levels were measured in humans and dogs following the intraduodenal instillation of hydrochloric acid. IRS levels rose after acid in both instances, but a concomitant rise in peripheral IRI levels was not noted. Premedication of the humans with Scopolamine prevented a rise of IRS in the human subjects. It is concluded that the endovenous release of IRS alone does not result in increased IRI levels in peripheral blood and that IRS release may be under vagal control.

Animals↗

Serum immunoreactive gastrin in rheumatoid arthritis. Further observations on its identity, clinical specificity, and relationship to gastric function.

Serum immunoreactive gastrin is raised in some patients with rheumatoid arthritis (RA). In this paper paired samples taken within 30 minutes of each other show that this phenomenon is reproducible. Dilution curves show identity between gastrin from RA patients and from patients with no RA, and the raised immunoreactive gastrin concentration is demonstrable in patients who do not have chronic atrophic gastritis and in whom both basal and stimulated acid output concentrations are normal. Samples of gastric mucous membrane obtained from the body of the stomach and gastroscopy under direct vision in 18 patients with raised serum immunoreactive gastrin concentrations were normal.

Arthritis, Rheumatoid↗

The role of enteric hormones in glucose homeostasis.

A brief review is given of the large numbers of hormones in the pancreas and gut. The concept of the 'entero-insular' axis is discussed and a critical appraisal is given of the claims for various proposed insulinotropic gut hormones. Gastric-inhibitory polypeptide appears at the present time to occupy a leading role in the entero-insular axis. Glucagon-like substances and vasoactive intestinal peptide are of importance in glucose homeostasis by having direct effects on carbohydrate metabolism. The study of the release of gut hormones after food ingestion would indicate that pancreatic glucagon exerts control on glucose hemeostasis during food ingestion, whereas gastric-inhibitory polypeptide may regulate insulin secretion after eating.

Animals↗