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Biomedical subjects

S W Coppack

Publications and source records attributed to S W Coppack.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1991

The natural history of diabetic femoral neuropathy.

Diabetic femoral neuropathy is an uncommon, unpleasant and sometimes disabling condition, on account of both pain and muscular atrophy, whose long-term prognosis has not previously been documented. We have reviewed a group of 27 patients up to 14 years (median 62 months) after diagnosis; 18 of these were re-examined after an average of nearly 4 years (median 45 months). The condition was more common in non-insulin-dependent diabetics (88 per cent), in men (59 per cent) and in older patients (median age at diagnosis 64 years). The neuropathy was bilateral (10 cases) or unilateral (17 cases); five patients with unilateral neuropathy developed femoral neuropathy on the opposite side, usually within a few weeks of the first episode. Recovery was apparent after 3 months and usually complete by 18 months; only two of the 27 patients had severe relapses. No patients remained disabled, although there were minor residual symptoms and signs in half of the patients (2 cm reduction in thigh circumference and diminished reflexes). The outlook for femoral neuropathy, even in its most severe form, is therefore very good: residual features are demonstrable but do not cause symptoms, and relapses after the first few weeks are very rare.

Adult↗
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

Pharmacokinetic and pharmacodynamic studies of glibenclamide in non-insulin dependent diabetes mellitus.

1. The pharmacokinetic and pharmacodynamic properties of oral glibenclamide have been studied in 31 hospitalised in-patients and 79 ambulant out-patients with diabetes mellitus. 2. Breakfast was found to have no significant influence on the kinetic behaviour of glibenclamide or on the effect of this drug on blood glucose utilisation. 3. The time course of glibenclamide kinetics after 20 mg dosing was adequately described by a two-compartment open model, yielding mean half-lives of 3.3 +/- 1.5 h (t1/2, lambda 1) and 9.7 +/- 1.2 (t1/2, z) for the initial and terminal elimination phases respectively. 4. No significant accumulation or change in kinetic profile occurred in patients who had normal renal and hepatic function, were treated continuously with glibenclamide, and then rechallenged after 8-12 weeks. 5. Despite inter-individual variations in drug absorption, peak plasma concentrations (Cmax) and the area under the plasma concentration-time curve (AUC(0-24] were dose-dependent over the dose range 5-20 mg. No significant dose-response behaviour was observed in respect of glucose utilisation, suggesting that there is little clinical benefit in using doses of glibenclamide above 5 mg day-1. 6. Comparison of plasma glibenclamide concentrations at different time-bands following doses of 5 and 10 mg showed a wider range in ambulant out-patients than in age-, sex-matched in-patients treated with the same dosages of drug. Mean plasma drug concentrations attained at all time bands up to 8 h after dosing were higher in out-patients than in in-patients, suggesting a tendency to 'over-compliance' by patients in anticipation of attendance at clinic.

Administration, Oral↗
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↗
PubMed1990

Application of minimal models to measuring insulin sensitivity.

Bergman's minimal model of glucose dynamics was used to analyse intravenous glucose tolerance tests in non-diabetic and non-insulin dependent diabetic subjects (NIDDM). This analytical approach yielded an index of insulin sensitivity in 63% of the non-diabetic and 15% of NIDDM subjects. When the model was constrained to search for the most likely parameter solutions, all the non-diabetic and 96% of the diabetic plasma insulin-glucose curves could be solved. A comparison of the insulin sensitivity index derived from this constrained minimal model against the metabolic clearance rate of glucose during a hyperinsulinaemic clamp carried out on the same subjects showed a correlation of 0.84 (P less than 0.01, N = 12 normal subjects) and 0.65 (P less than 0.001, N = 21 NIDDM patients). We conclude that this modification of the minimal model may improve the number of intravenous glucose tolerance tests capable of systematic analysis in NIDDM subjects, giving a measure of insulin sensitivity that correlates with more established measures of this parameter.

Blood Glucose↗
PubMed1990

Intravenous glucose tolerance and mortality in non-insulin-dependent diabetes mellitus.

Two hundred and forty-nine patients with non-insulin-dependent diabetes were entered into a prospective study at diagnosis and examined at presentation and one, three, and five years later. Ten years after diagnosis, 34 patients were known to be dead and 214 alive. A number of factors were significantly associated with survival on univariate analysis and appeared to form two independent intra-related groups: a 'metabolic' group and a 'degenerative condition' group. Multivariate analysis of these two groups showed that glucose tolerance (the rate constant KG for decrease in plasma glucose concentration after its intravenous injection) was significantly related to survival in the 'metabolic' group, and age, blood pressure and anti-hypertensive therapy were significant in the 'degenerative' group of factors. A low KG value was more strongly associated with prognosis than any other factor. Values from the one year review were prognostically more useful than initial or later values. Indices of insulin secretion were similar irrespective of whether patients survived or died, and so we believe the lower KG values of dead patients were due to impaired insulin sensitivity. A regression equation using the above factors correctly allocated survival outcome in 81% of subjects.

Blood Glucose↗
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

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↗