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Biomedical subjects

A J Barnes

Publications and source records attributed to A J Barnes.

At least 55 records · Page 3Linked to original sources

Ketoacidosis in pancreatectomized man.

We investigated the importance of glucagon in the development of diabetic ketoacidosis by withholding insulin from six patients with juvenile-type diabetes and four totally pancreatectomized subjects. Patients were fasting and had previously been maintained on intravenous insulin for 24 hours. In diabetic patients plasma glucagon concentrations rose sharply after withdrawal of insulin, and the increases were accompanied by a rise in blood ketone concentration of 4.1+/-0.7 (S.E.M.) and blood glucose concentration of 12.5+/-1.8 mmol per liter by 12 hours. In the pancreatectomized patients, despite the absence of measurable glucagon, blood ketones rose by 1.8+/-0.8 and blood glucose by 7.7+/-1.5 mmol per liter. Thus, glucagon is not essential for the development of ketoacidosis in diabetes, as has previously been suggested, but it may accelerate the onset of ketonemia and hyperglycemia in situations of insulin deficiency.

Acetoacetates↗

Mechanism of pancreatic polypeptide release in man.

Pancreatic polypeptide (P.P.) is a potent hormonal peptide which has been isolated from the pancreas. Its role in human physiology and pathology is not yet established. After a standard hospital lunch the plasma concentration of P.P. showed a rapid and identical rise in 10 healthy controls, 11 duodenal-ulcer patients, and 6 post-vagotomy patients but remained undetectable in 4 totally pancreatectomised subjects. In contrast plasma-P.P. was unaffected by intravenous administration of glucose, aminoacids, or fat. However, during intravenous infusion of caerulein, a cholecystokinin analogue, P.P. rose by nearly five-fold, and an even greater rise was seen after intravenous injection of Boots secretin. In 19 duodenal-ulcer patients insulin hypoglycaemia produced a rapid rise in plasma-P.P. but this did not occur in any of the 17 patients studied after a truncal vagotomy. Thus P.P. is released by oral but not intravenous nutriments and the existence of an entero-P.P. axis is postulated. One component of this axis may be the vagal innervation but the normal postprandial rise seen after vagotomy suggests that other control mechanisms, such as the intestinal hormones, are more important.

Adult↗

Persistent metabolic abnormalities in diabetes in the absence of glucagon.

In order to investigate the contribution of glucagon to the abnormalities of carbohydrate and lipid metabolism in diabetes, hormones and metabolites were measured in response to IV arginine in 5 juvenile onset (control) diabetics and 5 totally pancreatectomised subjects. In the basal state, both control diabetics and pancreatectomised patients showed abnormally elevated levels of plasma glucose, blood 3-hydroxybutyrate, glycerol and plasma free fatty acids (NEFA), although no glucagon was detectable in the plasma of the pancreatectomised subjects. Blood concentrations of the gluconeogenic precursors alanine and glycerol were higher pancreatectomised patients than in the diabetics. Following infusion of arginine, the rise in glucagon observed in the diabetics was accompanied by a significant increase in plasma glucose and a fall in blood lactate when compared to the pancreatectomised subjects. In spite of the rise in glucagon in the control diabetics, no sigficant change was found in the concentrations of ketone bodies, glycerol or NEFA. Thus glucagon does not seem to have a primary role in producing the metabolic abnormalities of diabetes.

Adult↗

Impaired red cell deformability in peripheral vascular disease.

By means of a recently developed technique, red-cell deformability was measured in 44 patients with peripheral vascular disease and in 44 age and sex matched normal control subjects. 28 patients had intermittent claudication and 16 rest pain or gangrene. The ability of the red cells to deform was significantly reduced in patients and significantly less in patients with rest pain or gangrene than in those who only had intermittent claudication. A reduction in red-cell deformability by retarding blood-flow through the microcirculation may be an important factor in states of peripheral vascular insufficiency.

Aged↗

Pancreatectomised man: A model for diabetes without glucagon.

The proposition that glucagon plays an essential part in maintaining hyperglycaemia in diabetes has been investigated by the study of 5 totally pancreatectomised subjects and 5 age and sex matched insulin-dependent diabetic patients. True basal glucagon values were obtained by the use of a new affinity chromatography technique. The mean fasting plasma-glucose levels of the pancreatectomised subjects was 251 +/- 46 mg/dl. The mean fasting plasma-glucagon level was not significantly elevated above zero (1-3 +/- 0-6 pmol/l) and showed no change following arginine. In the 5 insulin-dependent diabetics the mean fasting plasma-glucagon level of 17-2 +/- 5-3 pmol/l rose to a maximum at 25 minutes of 103-6 +/- 27-5 pmol/l during infusion of arginine. These findings imply the absence of a significant number of normally functioning alpha cells in extrapancreatic sites in man and demonstrate that pronounced hyperglycaemia may occur in the absence of glucagon. Glucagon is probably not of primary importance in the hyperglycaemia of insulin-dependent diabetics.

Adult↗

Distribution and release of human pancreatic polypeptide.

A simple and reliable radioimmunoassay has been developed for a new gut hormone, HPP. In the primate 93% of the total PP was found in the pancreas with a small amount throughout the remaining gastrointestinal tract. HPP has been shown to be produced by a number of pancreatic apudomas and their metastases. The immunoreactive PP from these tumours and from normal pancreas was chromatographically indistinguishable from the pure peptide. The plasma PP concentration rose rapidly after a meal in normal subjects and was still raised six hours later. Fasting plasma PP levels in patients with PP cell containing pancreatic endocrine tumours were higher than even the postprandial level in normal subjects. PP measurements is thus useful in diagnosis of pancreatic endocrine tumours.

Animals↗

Is glucagon important in stable insulin-dependent diabetics?

The role of glucagon has been evaluated in the everyday regulation of carbohydrate and lipid metabolism in insulin-dependent diabetic patients. Plasma concentrations of glucagon, growth hormone, cortisol, glucose, and free fatty acids and blood concentrations of glycerol, 3-hydroxybutyrate, acetoacetate, alanine, pyruvate, and lactate were measured in 38 fasting diabetic subjects deprived of their usual morning dose of insulin. The measurements were repeated in 25 of these patients after a further 3 hours of insulin deprivation and in 6 patients again at 6 hours. There was no correlation between the initial fasting levels of plasma-glucagon and those of the other biochemical measurements including glucose and ketone bodies. Furthermore, no correlation was found between changes in these measurements and in plasma-glucagon over a period of 3 or 6 hours. These findings suggest that glucagon is unlikely to play a role of primary importance in blood-glucose homoeostasis or ketone-body metabolism in ambulant insulin-dependent diabetic patients.

Adolescent↗