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Biomedical subjects

K N Frayn

Publications and source records attributed to K N Frayn.

At least 145 records · Page 8Linked to original sources
PubMed1991

Dose-response relationships for the effects of insulin on glucose and fat metabolism in injured patients and control subjects.

1. Twenty-four patients were studied at around 7 days after musculoskeletal injuries in order to define the nature of the impairment of sensitivity to insulin. Insulin was infused at 6, 35, 200 or 1200 m-units min-1 m-2 for 2 h and the plasma glucose concentration was 'clamped' at 5 mmol/l. Forearm (uninjured) glucose extraction and blood flow were measured, and whole-body substrate oxidation and energy production rates were assessed by indirect calorimetry. The patients were compared with normal control subjects. 2. Plasma insulin concentrations during infusion were similar in patients and control subjects, showing a similar metabolic clearance of insulin. At each infusion rate, the rate of glucose infusion needed to maintain euglycaemia was less in the patients than in the control subjects. The dose-response curve for whole-body glucose infusion rate against plasma insulin concentration showed diminished sensitivity and diminished maximal response in the patients. A similar pattern was seen for forearm glucose uptake, with a marked impairment of both sensitivity to insulin and maximal responsiveness. 3. The resting metabolic rate was increased in the patients compared with the control subjects, but failed to respond to insulin infusion, so that final metabolic rates were similar in patients and control subjects. At the higher insulin infusion rates, the final rate of whole-body oxidation of carbohydrate was significantly less in the patients than in the control subjects, and that of fat was significantly greater.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Amino acid metabolism in human subcutaneous adipose tissue in vivo.

1. Arteriovenous differences for alanine, glutamate and glutamine were measured across subcutaneous adipose tissue and forearm muscle in normal subjects. 2. After an overnight fast, adipose tissue showed net production of alanine and glutamine and uptake of glutamate in each of 11 subjects. 3. In seven subjects, adipose tissue blood flow was measured and the measurements were continued for 6 h after eating a mixed meal. The pattern of amino acid metabolism across the adipose tissue was remarkably little disturbed after the meal, except for a short period of apparent uptake of alanine as the concentration of that amino acid rose. 4. The pattern of amino acid metabolism across adipose tissue was qualitatively similar to that across the forearm, although it differed quantitatively in that glutamate uptake was more prominent (compared with glutamine release) in the adipose tissue. 5. The rates of alanine and glutamine release observed suggest that adipose tissue may play a substantial role in the whole-body production of these amino acids.

Adipose Tissue↗
PubMed1991

Effect of insulin on intracellular pH and phosphate metabolism in human skeletal muscle in vivo.

1. 31P nuclear magnetic resonance spectroscopy and the hyperinsulinaemic-euglycaemic clamp were used simultaneously to assess the effect of insulin on intracellular pH and the major phosphorus-containing metabolites of normal human skeletal muscle in vivo in four normal subjects. 2. Insulin and glucose were infused for 120 min. Plasma insulin increased approximately 10-fold over preclamp levels (5.6 +/- 0.9 m-units/l pre-clamp and 54 +/- 5 m-units/l over the last hour of infusion; mean +/- SEM, n = 4). Plasma glucose concentration did not change significantly (5.4 +/- 0.2 mmol/l pre-clamp and 5.5 +/- 0.1 mmol/l over the last hour of infusion). 3. Insulin and glucose infusion resulted in a decline in the intracellular pH of forearm muscle of 0.027 +/- 0.007 unit/h (P less than 0.01), whereas in control studies of the same subjects, pH rose by 0.046 +/- 0.005 unit/h (P less than 0.001). 4. In the clamp studies, intracellular inorganic phosphate concentration rose by 18%/h, whereas ATP, phosphocreatine and phosphomonoester concentrations did not change. In plasma, inorganic phosphate concentration was 1.16 +/- 0.05 mmol/l before infusion, and this decreased by a mean rate of 0.14 mmol h-1 l-1. No change was observed in any of these intracellular metabolites in the control studies. 5. The results show that, under physiological conditions, insulin does not raise intracellular pH in human muscle, and thus cannot influence muscle metabolism by this mechanism. The results also suggest that insulin causes a primary increase in the next flux of inorganic phosphate across the muscle cell membrane.

Adult↗
PubMed1991

Peripheral triacylglycerol extraction in the fasting and post-prandial states.

1. Triacylglycerol extraction by subcutaneous adipose tissue and forearm muscle was studied in nine normal subjects after an overnight fast and after the consumption of a mixed meal. 2. There was an inverse correlation between the total plasma fractional triacylglycerol extraction across the adipose tissue and the fasting arterial plasma triacylglycerol concentration. In contrast, there was no correlation between the lower fractional triacylglycerol extraction across the forearm muscle and the fasting plasma triacylglycerol concentration. 3. Chylomicron-triacylglycerol concentrations in arterial(ized) plasma increased post-prandially and peaked at 240-300 min. There was a comparable increase in the very-low-density lipoprotein-triacylglycerol concentration, peaking at 300 min. 4. Clearance of chylomicron-triacylglycerol by adipose tissue increased after the meal (P less than 0.05). In contrast, the clearance of very-low-density lipoprotein-triacylglycerol by adipose tissue decreased post-prandially (P less than 0.05). 5. Although there was significant uptake of chylomicron-triacylglycerol by the forearm muscle post-prandially, this was less than by the adipose tissue. Very-low-density lipoprotein-triacylglycerol was unaffected by passage through the forearm muscle at any time. 6. We conclude that the extraction of lipoprotein-triacylglycerol by human adipose tissue is important in determining the fasting plasma triacylglycerol concentration. Chylomicron-triacylglycerol, appearing in the plasma post-prandially, may compete with very-low-density lipoprotein-triacylglycerol for clearance by adipose tissue lipoprotein lipase, and this mechanism may explain, at least in part, the post-prandial rise in very-low-density lipoprotein-triacylglycerol. Forearm muscle, in contrast, appears to play a much smaller role in the extraction of plasma triacylglycerol, especially that in the very-low-density lipoprotein fraction.

Adipose Tissue↗
PubMed1991

Factors controlling fat mobilization from human subcutaneous adipose tissue during exercise.

To investigate possible factors that limit fat utilization during exercise, arteriovenous differences of plasma nonesterified fatty acids (NEFA) and glycerol were measured across the subcutaneous adipose tissue of the anterior abdominal wall in nine subjects who exercised for 60 min at 50-70% of their maximal O2 consumption. The large gradient of NEFA concentration from adipose tissue venous to arterial plasma increased throughout the exercise period. Maximal plasma NEFA concentrations in adipose venous drainage were reached postexercise (median 3,800 mumol/l), with a median NEFA-to-albumin molar ratio of 5.7. Fractional reesterification of fatty acids within the tissue (assessed from the ratio of NEFA to glycerol release) was 20-30% in the basal state and declined during exercise. After exercise there was apparently negative reesterification, implying release of NEFA retained in adipose tissue during exercise. Although these findings challenge current views on the regulation of NEFA release, they are in agreement with the concept of supply of fatty acids from adipose tissue as the major factor limiting fat oxidation during sustained exercise.

Adipose Tissue↗
PubMed1990

Arteriovenous differences across human adipose and forearm tissues after overnight fast.

Measurements of arteriovenous differences across subcutaneous abdominal tissue (mainly adipose) and deep forearm tissue (mainly muscle) were made on 25 occasions in normal subjects after an overnight fast. Adipose tissue was shown to be strongly lipolytic (releasing nonesterified fatty acids and glycerol), to clear circulating triacylglycerol, glucose, ketone bodies and acetate, and to produce lactate. Uptake of circulating carbohydrate and ketones was sufficient to account for only 51% of the adipose tissue oxygen consumption, implying that adipose tissue utilizes fuel(s) stored within it. The mean fractional re-esterification rate of fatty acids in adipose tissue was 13% to 19%. Arteriovenous differences were converted to fluxes of carbon atoms to compare the movements of different fuels. (Amino acids were not included in these calculations.) Adipose tissue after an overnight fast was a net exporter of carbon, whereas in resting muscle the uptake of carbon atoms from circulating carbohydrate and lipid fuels approximately balanced the CO2 production. Fatty acids were the main form in which carbon left adipose tissue, and the main source of carbon atoms entering the resting forearm.

Acetates↗
PubMed1990

Metabolic responses of forearm and adipose tissues to acute ethanol ingestion.

Although excess ethanol consumption is often considered to lead to adiposity, the metabolic routes by which this might occur are not clear. We have investigated some metabolic consequences of acute ethanol ingestion by measuring arteriovenous differences across forearm muscle and subcutaneous adipose tissue for 6 hours after ingestion of 47.5 g ethanol, in seven normal subjects fasted overnight. The expected systemic effects of ethanol ingestion were observed: slight lowering of the plasma glucose concentration, depression of plasma nonesterified fatty acid (NEFA) concentrations, and elevation of the blood lactate/pyruvate and 3-hydroxybutyrate/acetoacetate ratios. There was a marked reduction in blood total ketone bodies in relation to plasma NEFA concentrations. However, the only major change observed in peripheral tissue metabolism was an increased uptake of acetate into forearm muscle, equivalent, in whole-body terms, to only 3% of the ethanol load. Adipose tissue appeared to show a reduced cytoplasmic state in that it exported an increased ratio of lactate to pyruvate after ethanol ingestion. However, this reduced state did not lead to increased fatty acid reesterification within adipose tissue. No mechanism was clearly identified whereby ethanol ingestion might lead to net deposition of triacylglycerol in adipose tissue.

Acetates↗
PubMed1990

Postprandial substrate deposition in human forearm and adipose tissues in vivo.

1. Substrate movements in forearm muscle and subcutaneous adipose tissue were studied, by measurement of arteriovenous differences and blood flow, in seven normal subjects after an overnight fast and then for 6 h after ingestion of a mixed meal. Overall substrate balances were examined in terms of the flux of gram-atoms of carbon. 2. As found previously, the forearm was approximately in carbon balance (import equal to export) after the overnight fast, whereas adipose tissue was a net exporter of carbon, mainly in the form of non-esterified fatty acids. 3. After the meal, arterialized plasma concentrations of glucose and lactate rose sharply (peak at 60 min), whereas those of non-esterified fatty acids and glycerol fell (nadir at 60-120 min). Plasma triacylglycerol concentrations rose slowly to peak at 240 min;much of this rise was accounted for by a rise in the chylomicron fraction. 4. Both tissues took up glucose at an increased rate after the meal. Release of non-esterified fatty acids and glycerol from adipose tissue was suppressed. Clearance of triacylglycerol by both tissues increased after the meal, but was more marked in adipose tissue, where the fractional extraction of chylomicron-triacylglycerol reached 44% at 240 min. 5. The forearm rapidly became a considerable net importer of carbon, and remained so until 6 h after the meal when it was again in approximate carbon balance. Glucose uptake dominated the forearm carbon balance. Adipose tissue was a net importer of carbon from 30 min until 5 h after the meal and then reverted to net export. Clearance of triacylglycerol carbon made the largest contribution to this positive balance, but towards the end of the study this was increasingly counterbalanced by simultaneous non-esterified fatty acid release.

Adipose Tissue↗
PubMed1990

Metabolic effects of low-dose dopamine infusion in normal volunteers.

1. Dopamine in 5% (w/v) D-glucose was infused into five healthy male volunteers at doses of 2, 5 and 10 micrograms min-1 kg-1 over three sequential periods of 45 min each. 2. Oxygen consumption, respiratory exchange ratio, blood glucose concentration and plasma levels of free fatty acids, glycerol, lactate, dopamine, adrenaline and noradrenaline were measured. The results were compared with values obtained during infusion over the same time period of the corresponding volumes of 5% (w/v) D-glucose alone. 3. Energy expenditure calculated from the oxygen consumption and the respiratory exchange ratio was higher than control values during infusion of dopamine (P less than 0.001, analysis of variance) specifically at a rate of 10 micrograms min-1 kg-1 (P less than 0.05) when it was 14% higher, but not at a rate 2 of or 5 micrograms min-1 kg-1. The plasma noradrenaline concentration was 74 and 230% and the blood glucose concentration was 21 and 36% higher than control values at 5 and 10 micrograms of dopamine min-1 kg-1, respectively (P less than 0.01). At 10 micrograms of dopamine min-1 kg-1 the plasma free fatty acid concentration was 70% and the plasma glycerol concentration was 80% higher than during the control infusion (P less than 0.01). The respiratory exchange ratio and the plasma lactate concentration were the same in the two groups and did not alter during the dopamine infusion. The plasma adrenaline concentration rose significantly (P less than 0.01), but only transiently, during dopamine infusion at a rate of 2 micrograms min-1 kg-1. 4. Dopamine at low doses has metabolic effects. It increases the blood glucose concentration and the circulating noradrenaline level at an infusion rate of 5 micrograms min-1 kg-1. It increases energy expenditure and circulating free fatty acid and glycerol levels at an infusion rate of 10 micrograms min-1 kg-1, presumably due to stimulation of lipolysis.

Adult↗
PubMed1990

Stability of plasma glucose during storage.

Plasma glucose concentrations were found to decrease during storage. This phenomenon was not method-dependent; it was demonstrated using both a Beckman Glucose Analyser 2 (based on glucose oxidase) and a hexokinase-based technique on a centrifugal analyser. The loss of glucose was typically of the order of 10% in plasma frozen for periods from 24 h to 14 months. Repeated freezing and thawing (weekly for 1 month) did not produce additional loss of glucose compared with aliquots thawed for the first time at 1 month. Fluoride did not reduce the loss of glucose. Glucose was also lost from frozen neutralized perchloric acid extracts of blood (mean +/- SD: 7 +/- 2 per cent over 1 year). We conclude that this variable loss of glucose on storage may complicate the interpretation of metabolic research procedures.

Blood Glucose↗
PubMed1990

Human adipose tissue glycogen levels and responses to carbohydrate feeding.

Glycogen has long been known to be present in adipose tissue, but its role is not clear. It has not been measured in human adipose tissue. We have investigated methods for its measurement using rat adipose tissue, and measured levels in humans. Glycogen in rat adipose tissue was found to be labile, necessitating rapid sample preservation. Levels in random biopsies of human adipose tissue were variable, but consistent with values for other species (0.06-0.78 mg/g wet weight; n = 5). After overnight fast, consistent low levels were found (0.04-0.08 mg/g wet weight; n = 6); these increased after eating a high-carbohydrate diet (800 g/d for 2.5 d), to 0.10-1.95 mg/g wet weight (P less than 0.05). Human adipose tissue glycogen appears to play a minor role in whole-body glucose homeostasis, but may have an important local role in the regulation of lipogenesis.

Adipose Tissue↗