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Biomedical subjects

K D Buchanan

Publications and source records attributed to K D Buchanan.

At least 181 records · Page 10Linked to original sources

A histological study of intrasplenic transplanted neonatal rat pancreas and of adjacent adipose tissue proliferation.

Proliferation of adipose tissue adjacent to intrasplenic transplants of whole isogeneic neonatal rat pancreas has consistently been noted. In this study over a period of 18 months there was a progressive increase in the amount of fatty tissue in the vicinity of surviving transplants. Immunohistochemistry demonstrated the presence of insulin, glucagon, somatostatin and pancreatic polypeptide within islet cells in long term grafts. Electron microscopy demonstrated a close association between islets and lipid droplets. Ductal elements within the transplants survived and showed close association with endocrine cells, but exocrine pancreatic tissue degenerated rapidly. Radioimmunoassay of extracts from surviving transplants in isogeneic rats confirmed the presence of high levels of insulin and glucagon after transplantation. In contrast, allogeneic intrasplenic transplants of rat pancreas failed to survive and showed no evidence of adipose tissue proliferation. Furthermore, isogeneic intrasplenic transplants of both adult rat fat and adrenal gland also failed to demonstrate adipocyte proliferation. It would appear that the presence of both adipocytes and pancreatic endocrine cells, particularly B cells, are required for the proliferation of adipocytes at the graft site.

Adipose Tissue↗

The effect of intensive dietary therapy on serum high density lipoprotein cholesterol in patients with Type 2 (non-insulin-dependent) diabetes mellitus: a prospective study.

Intensive dietary therapy in 57 newly diagnosed Type 2 (non-insulin-dependent) diabetic patients led to an increase, compared with pre-treatment levels, in serum high density lipoprotein (HDL) cholesterol and the HDL/total cholesterol ratio after 3 and 6 months (0.05 less than p less than 0.1). The increase in HDL cholesterol was related to the degree of weight loss achieved. In 28 patients whose weight decreased by greater than or equal to 10% average body weight during the 6 months, HDL cholesterol rose from 1.22 +/- 0.06 to 1.36 +/- 0.06 mmol/l (p less than 0.001), whereas patients who lost less weight showed no significant increase in HDL cholesterol. The increase in mean serum HDL-cholesterol levels in female patients was associated with a mean weight reduction of 12.1% average body weight. Patients who were obese at diagnosis lost more weight during the study than non-obese patients (mean 13.2 versus 5.6% average body weight), and showed a significant increase in serum HDL-cholesterol levels. We conclude that intensive dietary therapy may lead to a less atherogenic lipid profile in Type 2 diabetes, particularly in patients who achieve a major weight reduction.

Adult↗

Glucose tolerance in the elderly: the role of insulin and its receptor.

Oral glucose tolerance tests were performed in young and elderly subjects with minimal risk factors for diabetes mellitus. Compared to the normal glucose tolerance in the young there was a 45% rate of impaired tolerance in the elderly. Fasting insulin levels were significantly lower in the elderly but post-glucose insulin responses in the first hour were similar in young and elderly subjects. Peripheral insulin action was assessed in terms of the 125 monoiodoinsulin binding to specific insulin receptor sites on circulating lymphocytes in the young, the elderly and a group of age and sex matched obese maturity-onset diabetics. Specific insulin binding was not significantly different in the elderly than in the young but was significantly lower in the diabetics than the young and the elderly. The results suggest that neither defective insulin binding are major causative factors in the reduced glucose tolerance of the elderly.

Adult↗

Regulation of plasma immunoreactive glucagon in obese hyperglycaemic (ob/ob) mice.

This study examines the role of glucagon in the pathogenesis of the obese hyperglycaemic (ob/ob) syndrome in mice. Plasma C-terminal immunoreactive glucagon concentrations were measured in fed and fasted ob/ob mice at different ages between 5-40 weeks, and in 20-week-old mice after the administration of established stimulators and inhibitors of glucagon secretion. Plasma glucagon concentrations were inappropriately raised irrespective of age, nutritional status and the accompanying prominent changes in plasma glucose and insulin concentrations. Glucose suppressed plasma glucagon in the fed but not the fasted state, suggesting a dependence on the marked hyperinsulinaemia associated with feeding. Administration of 0.25 units insulin/kg to fasted mice failed to affect plasma glucagon and glucose concentrations. Increasing the dose to 100 units/kg restored the normal suppressive actions of insulin. Fasted mice showed an exaggerated glucagon response to arginine but not to the parasympathomimetic agent pilocarpine. Fed mice displayed normal plasma glucagon responses to the sympathomimetic agents noradrenaline and adrenaline. Administration of insulin antiserum or 2-deoxy-D-glucose raised plasma glucagon concentrations of fed mice. Contrary to the lack of suppression by glucose in the fasted state, heparin-induced increase in free fatty acids reduced plasma glucagon concentrations. This study demonstrates inappropriate hyperglucagonaemia and defective A-cell function in ob/ob mice. The extent of the abnormality is exacerbated by fasting and appears to result from insensitivity of the A-cell to the normal suppressive action of insulin.

Animals↗

The gastro-entero-pancreatic hormone response to fasting in obesity.

A comparison of the metabolic and gastroentero-pancreatic hormonal responses of ten obese and eight lean subjects to 12 h and 36 h fasts has been made. Each subject was given a 50 g oral glucose tolerance test at the end of both 12 h and 36 h starvation. After the 12 h fast blood glucose and 3-hydroxybuty-rate were similar in each group but blood glycerol was 30% higher in the obese subjects. Plasma insulin and vaso-active intestinal polypeptide were also higher in the obese subjects after 12 h starvation. After 36 h starvation in the lean subjects blood glucose was unchanged but on refeeding with 50 g oral glucose, glucose tolerance was impaired. In the same group blood glycerol and 3-hydroxybutyrate rose after 36 h starvation. Plasma glucagon, secretin and vaso-active intestinal polypeptide rose after 36 h starvation in the lean subjects but plasma insulin was unchanged. Refeeding with oral glucose suppressed the increased plasma glucagon, secretin and vaso-active intestinal polypeptide. After the 36 h fast in the obese subjects, blood glucose was unchanged, blood glycerol fell, but blood 3-hydroxybutyrate rose although to a reduced level in comparison with the lean subjects. In the obese group there was no change in plasma glucagon, secretin or vaso-active intestinal polypeptide after 36 h starvation, although plasma insulin fell. The results show different metabolic and gastro-entero-pancreatic hormonal responses to fasting in lean and obese human subjects and suggest an important metabolic role of glucagon, secretin and vaso-active intestinal polypeptide during starvation.

3-Hydroxybutyric Acid↗

Changes in N-terminal glucagon-like immunoreactivity and insulin during short-term gluten challenge in childhood coeliac disease.

Sixteen patients (aged 3.5-14.3 years) with normal jejunal mucosa, originally diagnosed as having coeliac disease at least 18 months before, were started on gluten challenge. The 'end point' of challenge was significant deterioration in jejunal mucosa morphologically and morphometrically. Studies carried out both before and after challenge included intestinal absorption of D-xylose and glucose, and release of insulin and N-terminal glucagon-like immunoreactivity (N-GLI). After gluten challenge, there were significant increases in plasma N-GLI at both 45 (P less than 0.05) and 120 minutes (P less than 0.03) after oral glucose. Significant reduction occurred in glucose absorption at 45 minutes (P less than 0.04), in one-hour D-xylose absorption (P less than 0.01) and fasting serum cholesterol (P less than 0.01). Plasma N-GLI showed significant negative correlations with D-xylose absorption (P less than 0.003) and serum cholesterol (P less than 0.004).

Adolescent↗

The release of vasoactive intestinal peptide during altered mid-gut blood flow.

In a series of 17 dogs of which 6 were controls experiments were undertaken to measure arterial and portal vasoactive intestinal peptide (VIP) levels during reduced cephalic mesenteric artery flow states and following reperfusion of the ischaemic mid gut. The flow states examined were basal flow, 50 per cent of basal flow and 25 per cent of basal flow. Zero flow was examined for 20 min and reperfusion of the ischaemic mid gut for 20 min. Peripheral and portal VIP levels were found to be massively elevated during all the flow states studied but particularly during reperfusion of the ischaemic mid gut.

Anesthesia↗