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Biomedical subjects

K N Frayn

Publications and source records attributed to K N Frayn.

At least 163 records · Page 9Linked to original sources
PubMed1989

Changes in forearm blood flow at elevated ambient temperature and their role in the apparent impairment of glucose tolerance.

1. Antecubital venous plasma glucose and insulin concentrations after ingestion of 75 g of glucose were higher in six normal subjects when studied at an ambient temperature of 33 degrees C at an ambient temperature of 23 degrees C; the mean area under the glucose-time curve increased from 833 at 23 degrees C to 990 mmol min-1 at 33 degrees C, that for insulin from 5300 to 7900 m-units min 1-1. 2. Core temperature was elevated by 0.5 degree C at 33 degrees C ambient, although there was no marked stress response as judged by plasma levels of catecholamines, cortisol and growth hormone; at 2 h after glucose ingestion, mean noradrenaline levels were lower at 33 degrees C than at 23 degrees C (1.1 at 33 degrees C vs 1.8 nmol/l at 23 degrees C), adrenaline slightly higher (0.18 at 33 degrees C vs 0.09 nmol/l at 23 degrees C), cortisol and growth hormone unchanged. 3. Forearm blood flow was markedly elevated at 33 degrees C ambient (mean total flow 9.1 at 33 degrees C vs 1.8 ml min-1 100 ml-1 at 23 degrees C), as were antecubital venous partial pressure of oxygen (mean 10.1 at 33 degrees C vs 5.6 kPa at 23 degrees C) and oxygen saturation (mean 92% at 33 degrees C vs 70% at 23 degrees C). There was a positive correlation between oxygen saturation and area under the glucose tolerance curve. 4. In separate experiments, arterialized glucose concentrations were measured after glucose ingestion at 23 degrees C ambient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Metabolic characteristics of human adipose tissue in vivo.

1. A method was developed for sampling the venous drainage from the subcutaneous adipose tissue of the anterior abdominal wall. This is a large depot in many subjects, and seems well suited to such studies as it is completely separated from the venous drainage of the underlying muscle by the aponeurosis of the external oblique muscle. 2. Eight normal subjects were studied after an overnight fast, and for 120 min after ingestion of 75 g of glucose. Concentrations of substrates in the abdominal wall drainage were compared with those in arterialized blood and in forearm muscle drainage. 3. Non-esterified fatty acid and glycerol concentrations in the abdominal wall drainage were high (three to four times the arterial level) after overnight fast. After glucose ingestion, arterial and abdominal venous levels fell and the arteriovenous differences narrowed. The forearm showed uptake of non-esterified fatty acids when fasting but not after glucose ingestion, with no significant arteriovenous difference for glycerol at any time. 4. The abdominal wall tissues showed a small arteriovenous difference for glucose uptake during fasting, which increased after glucose ingestion. Although lactate was produced throughout, its molar ratio to glucose uptake was less than that reported for other superficial sites, suggesting only a minor contribution of skin metabolism. Forearm muscle showed a larger and more prolonged increase in arteriovenous difference for glucose uptake after the glucose load, but no consistent release or uptake of lactate. 5. We conclude that the tissue studied by this technique is predominantly adipose. This technique may have wide application in studies of the metabolic basis for body weight regulation in man.

Adipose Tissue↗
PubMed1989

Effects of insulin on human adipose tissue metabolism in vivo.

1. The metabolic effects of insulin on human adipose tissue were studied by combining the euglycaemic clamp technique with measurement of arteriovenous differences across the subcutaneous adipose tissue of the anterior abdominal wall. 2. Eight normal subjects were studied after an overnight fast, and for 120 min during infusion of insulin (mean arterialized plasma insulin 50-55 m-units/l). 3. During the insulin infusion, the arterialized and abdominal venous levels of both non-esterified fatty acids and glycerol fell, and the arteriovenous differences for the release of these substances narrowed. The fractional rate of re-esterification of fatty acids was around 20% in the fasting state and increased to almost 100% during hyperinsulinaemia. 4. In the fasting state the uptake of glucose and 3-hydroxybutyrate by adipose tissue could account for only 20% of the oxygen uptake. During insulin infusion, adipose tissue glucose uptake increased and could account for more than 100% of oxygen uptake, implying storage of glucose. 5. Net balances of different substrates across adipose tissue were examined by calculating fluxes in terms of microgram-atoms of carbon. In the fasting state adipose tissue was in marked negative carbon balance (because of the export of non-esterified fatty acids); during insulin infusion it just reached 'carbon balance'. These results were in contrast to those from a previous study of glucose ingestion, in which the adipose tissue showed marked positive carbon balance (net substrate deposition).

3-Hydroxybutyric Acid↗
PubMed1989

Effect of acetate infusion on energy expenditure and substrate oxidation rates in non-diabetic and diabetic subjects.

Sodium acetate was infused intravenously at 2.5 mmoles/min for 60 min into 6 normal subjects and 6 non-insulin dependent diabetic patients. In control experiments the same subjects received equimolar sodium bicarbonate infusions. Plasma non-esterified fatty acid and blood glycerol levels fell during acetate infusion in both groups, suggesting impairment of lipolysis. The respiratory quotient fell on acetate infusion as expected, although total energy expenditure was unaffected. If acetate oxidation was assumed to be 90 per cent of the infusion rate, then it accounted for about 40 per cent of total oxygen consumption; fat oxidation was reduced, whilst carbohydrate oxidation was unchanged. These results suggest that resting energy expenditure is maintained during acetate infusion since acetate replaces fat as an oxidative fuel, without affecting glucose oxidation. The reduction in fat oxidation appears to be due to reduced fat mobilization from adipose tissue. The metabolic effects of acetate infusion are similar in normal and in non-insulin dependent diabetic subjects.

Acetates↗
PubMed1989

Plasma triacylglycerol extraction in human adipose tissue in vivo: effects of glucose ingestion and insulin infusion.

Extraction of endogenous triacylglycerol (TAG) was measured across the subcutaneous adipose tissue of the abdominal wall and across forearm muscle in 16 studies on 13 normal subjects. After overnight fast there was significant TAG extraction across both adipose tissue (4 per cent) and muscle (1 per cent). After 75 g oral glucose (8 subjects), there was a rise in the arterial TAG concentration to a peak at 60 min, with a concomitant increase in extraction across adipose tissue (to 9 per cent). During insulin infusion (8 subjects; plateau insulin concentration 50-55 mU/l) with the plasma glucose 'clamped' at the fasting level, arterial TAG levels fell steadily, and extraction across adipose tissue and muscle decreased. The ability to measure triacylglycerol extraction by adipose tissue in vivo opens up many possibilities for metabolic and nutritional studies.

Adipose Tissue↗
PubMed1988

Energy metabolism during chronic endotoxin infusion in the rat, with special reference to free fatty acid turnover.

We have studied various aspects of whole-body energy metabolism during chronic endotoxin infusion in the rat. In particular, we studied free fatty acid kinetics using bolus injections of 14C-palmitate. The general response to 7 days of chronic endotoxin infusion could be divided into an initial 3- to 4-day period of illness with loss of appetite, followed by rapid recovery. Using saline-infused, pair-fed controls, the following observations were made throughout the 7-day period of endotoxin infusion: 1) Plasma free fatty acids, glycerol and 3-hydroxybutyrate concentrations were reduced; 2) plasma glucose concentrations were elevated; 3) free fatty acid production rates were unaffected; 4) metabolic clearance of free fatty acids was unaffected on day 1 but was significantly greater on days 3 and 7; 5) haematocrits and plasma volumes were elevated. The results suggest that the observed changes in circulating free fatty acid concentrations are more likely to be a consequence of haemodynamic alterations than of metabolic alterations.

3-Hydroxybutyric Acid↗
PubMed1988

Effects of chronic endotoxaemia on oxygen consumption at different ambient temperatures in the unanaesthetised rat.

Oxygen consumption has been measured at different ambient temperatures at intervals during the intravenous infusion of endotoxin (1 mg/kg.day-1) from a subcutaneously implanted osmotic minipump in unanaesthetised rats. On day 1 of the infusion oxygen consumption was elevated at ambient temperatures of 10, 28, and 31 degrees C but not at 20 degrees C, compared with pair-fed saline-infused controls. There was a significant negative correlation between oxygen consumption on days 1 and 3 and environmental temperature (10, 20, and 28 degrees C) in both groups, but the regression line describing the relation in endotoxin-infused rats was displaced above that for the saline-infused control without a change in slope. The "minimal observed" oxygen consumption, which is taken as an estimate of basal metabolic rate, was elevated by the infusion of endotoxin. The endotoxin-induced increase in "minimal observed" oxygen consumption was removed by indomethacin (5 mg/kg.sc) on day 1 of the infusion but was ineffective on days 3 and 7.

Animals↗
PubMed1987

Factors affecting the plasma insulin concentration shortly after accidental injury in man.

There are conflicting reports on plasma insulin concentrations in the acutely injured. Plasma insulin and glucose concentrations have been measured in 504 patients within 8 h of injury, and related to the severity of injury as assessed by the injury severity score (ISS). As in previous surveys of injured patients, an extremely wide range of insulin concentrations was found (2-141 mU/l). Most of the variability occurred at lower severities of injury. In very severely injured patients (ISS greater than or equal to 30), insulin concentrations were uniformly suppressed (less than 20 mU/l), especially in relation to the hyperglycaemia in these patients. Two small subgroups, patients dying within 3 h of injury and known psychiatric patients on psycho-active drugs, differed from the general pattern in displaying elevated insulin concentrations despite very severe injuries. The results bear out the idea that insulin secretion is usually acutely suppressed by adrenaline after severe injury; after less severe injuries, however, the response is much less uniform.

Accidents↗
PubMed1987

The disposal of intravenous glucose studied using glucose and insulin clamp techniques in sepsis and trauma in man.

Whole body glucose uptake and oxidation during a hyperglycemic clamp have been shown to be depressed in hypermetabolic septic patients compared to control subjects despite similar plasma insulin concentrations. Forearm glucose uptake was similarly impaired. Metabolic rate was not increased further by the glucose infusion in the patients although a 20% rise was elicited in the controls. This resistance to the effects of insulin was also clearly demonstrated in trauma patients using the euglycemic clamp technique. The maximal rate of glucose disposal after injury was half that found in controls and the pattern of response was consistent with the insulin resistance being a post-receptor defect.

Glucose↗
PubMed1987

Use of alumina columns to prepare plasma samples for liquid-chromatographic determination of catecholamines.

We describe an improved method of sample preparation for liquid chromatographic determination of plasma catecholamines. The catecholamines are extracted from plasma by using small, cheaply-made columns of alumina, with or without prior clean-up on commercially available ion-exchange columns. Advantages of this technique over the conventional batch-extraction method of using alumina are speed, convenience, and improved sample clean-up. In particular, the one-stage method we describe allows results to be reported within 20 min of receiving the sample.

Aluminum↗
PubMed1986

The role of catecholamines in the production of ischaemia-induced ventricular arrhythmias in the rat in vivo and in vitro.

The role of catecholamines in the production of ischaemia-induced ventricular arrhythmias in vivo and in vitro was studied using coronary artery ligation in the rat. Increases in plasma catecholamine concentrations during coronary artery ligation in pentobarbitone-anaesthetized animals were prevented by either acute adrenalectomy or chronic adrenal demedullation, but these procedures did not protect against the occurrence of ventricular arrhythmias. Thus plasma catecholamines were not obligatory mediators of arrhythmogenesis. Three protocols were used in vitro to evaluate the possible influence of intramyocardial release of noradrenaline, produced by the local conditions of ischaemia, on the production of ventricular arrhythmias. During coronary artery ligation in isolated perfused hearts, no enhanced output of 3H could be detected from [3H]-noradrenaline loaded hearts, even in the presence of inhibitors of catecholamine uptake processes, although washout of lactate from ischaemic regions was readily demonstrable. Both optical isomers of propranolol were equally effective in reducing the incidence of arrhythmias, implying a non-specific effect, since the (+)-isomer possesses considerably less beta-adrenoceptor blocking activity. The equipotency of optical isomers of propranolol combined with a lack of effect of atenolol suggested that arrhythmia production was not a consequence of beta-adrenoceptor stimulation. The alpha-adrenoceptor blockers phentolamine and prazosin, both exerted antiarrhythmic actions of similar potency, but phenoxybenzamine and trimazosin had no significant effects. An evaluation of the pharmacological properties of the alpha-adrenoceptor blockers showed that those drugs which had demonstrable local anaesthetic properties also exerted significant antiarrhythmic effects. No relationship was found between potency of alpha-adrenoceptor blockade and antiarrhythmic efficacy. The overall conclusion from these multifaceted approaches was that catecholamines were not necessary mediators of the early phase of ventricular arrhythmias in the rat.

Adrenal Medulla↗