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Biomedical subjects

U Smith

Publications and source records attributed to U Smith.

At least 199 records · Page 11Linked to original sources
PubMed1980

Reduced glucose incorporation to triglycerides following chronic exposure of human fat cells to growth hormone.

Using the tissue culture technique we have recently demonstrated that long-term exposure of human adipose tissue to human growth hormone (GH) in vitro leads to an impairment in glucose incorporation into triglycerides. This effect was further studied in the present investigation. Biopsies of human adipose tissue which had been cultured for one week with or without GH were studied in subsequent short-term incubations where the conversion of glucose to CO2 and to total lipids was determined. The formation of CO2 was not changed by previous exposure of the biopsies to GH whereas the incorporation of glucose into triglycerides was reduced by about one third. Total glucose metabolism, as determined from the sum of the two pathways, was significantly reduced. The activities of three glycolytic enzymes were determined in biopsies of human adipose tissue which had been cultured with or without GH for one week. The activity of phosphofructokinase was reduced, while the hexokinase and the glucose-6-phosphate dehydrogenase activities were unchanged. The diminished activity of phosphofructokinase, the enzyme considered to be rate-limiting for glycolysis in human fat cells, may be responsible for the decreased rate of glucose metabolism found.

Adipose Tissue↗
PubMed1980

Effect of beta-blockade on hormone release during hypoglycaemia in insulin-dependent diabetics.

Previous studies have shown that non-selective, but not beta 1-selective, beta-blockers prolong the duration of hypoglycaemia. In order to elucidate possible mechanisms key hormones as well as alanine levels were measured following insulin-induced hypoglycaemia in 7 insulin-dependent diabetics. The subjects were treated with placebo, propranolol (a non-selective agent) or metoprolol (a beta 1-selective drug) prior to the hypoglycaemia. Treatment with either beta-blocking agent led to higher levels of adrenaline, glucagon, cortisol and growth hormone during hypoglycaemia as compared to those reached on placebo. The adrenaline levels during placebo treatment in response to hypoglycaemia appeared less in these diabetics than that previously reported for non-diabetics. The plasma alanine levels were similar and decreased following insulin administration irrespective of type of treatment. The data show that the release of key glycogenolytic and gluconeogenic hormones is not inhibited by beta-blockers during hypoglycaemia but is instead augmented or, possibly, hormonal clearance is reduced. It is suggested that the delayed recovery in blood glucose on a non-selective beta-blocker is partly due to lack of gluconeogenic substrates such as lactate and glycerol.

Adrenergic beta-Antagonists↗
PubMed1980

Effects of refeeding on adipocyte metabolism in the rat.

Glucose metabolism in fat cells from fasted-refed rats and ad-libitum-fed controls were studied in the postabsorptive state. Two types of experiments were performed. First, each rat donated one epididymal fat pad and the metabolic results were expressed in relation to the number and size of fat cells of these tissues. Second, the other epididymal fat pad in the rats in each experimental group was pooled for experiments in duplicate where liberated fat cells were separated in fat-cell size classes, which enabled comparisons of metabolic activities at the same fat-cell size. Glucose incorporation into carbon dioxide and triglyceride glycerol and fatty acids were about equally elevated in absolute terms in the refed rats. In relative terms the increase was much more pronounced in carbon dioxide and fatty acids because these activities were very low in control rats. These results confirm previous results showing elevated metabolism after fasting-refeeding, and also demonstrate that this is an adaptation of fat-cell metabolism rather than a consequence of a higher cellular density of adipose tissue after fasting-refeeding with smaller fat cells. Adaptations of metabolism after fasting-refeeding might be of potential importance for elucidation of the cause of the rapid relapse after weight decrease of obese subjects with diminished fat-cell size.

Adipose Tissue↗
PubMed1980

Possible systemic metabolic effects of regional adiposity in a patient with Werner's syndrome.

A patient with Werner's syndrome, partial lipoatrophy and diabetes mellitus presented several of the metabolic alterations found in obesity and maturity-onset diabetes, in spite of a total body-fat mass which was markedly reduced when compared to randomly-selected women. The data show elevated blood sugar and free fatty acids, hyperinsulinemia, elevated glucaon and suppressed growth-hormone levels. Metabolic studies with isolated adipocytes show evidence of increased lipolytic response to catecholamines, diminished binding of insulin and decreased antilipolytic effect of this hormone. A striking feature of this patient's adipose tissue was the contrast between lipoatrophy in the subcutaneous tissue of the extremities and augmented abdominatl subcutaneous adipose tissue. The adipocyte size in this region was very large (1.6 micrograms lipid/cell) and among the largest ever recorded in this laboratory. It is proposed that a 'regional adiposity', particularly in the abdominal area, with enhanced adipocyte size and adipocyte metabolic contributions, may promote the metabolic events and alterations that are more typically observed in the generalized form of obesity.

Adipose Tissue↗
PubMed1980

Regulation of the number of insulin receptors in human fat cells.

Previous studies have shown that the ambient insulin concentration can regulate the number of insulin receptors. The concept implies that hyperinsulinemia may cause a reduced receptor number and cellular insulin resistance. The possible importance of this concept on the mode of treatment of diabetics was studied. Five insulin-dependent diabetics were studied under metabolic ward conditions while treated with one dose of long-acting insulin or with smaller amounts of short-acting insulin 30 min before meals. Adipose tissue samples were taken on each regime. The number of insulin receptors were increased in all subjects on the short-acting regime and this was coupled with an increased insulin sensitivity in the adipocytes. One probable reason for this finding is that the insulin levels were higher during the long-acting regime leading to an attenuated number of insulin receptors. The data show that short-acting insulin taken repeatedly in connection with meals leads to a more normal state and an increased peripheral insulin sensitivity as compared to a regime of one dose of long-acting insulin.

Adipose Tissue↗
PubMed1980

Adipose tissue cellularity in adulthood and its relation to childhood obesity.

A population sample totalling 1462 middle-aged women was studied in 1968-69. A re-study of the same women in 1974-75 comprised 1302 women. Body composition and adipose tissue cellularity were determined in a systematic subsample of 227 women and in a subsample of 76 obese women. There was a significant relation between body build in childhood (evaluated retrospectively as lean, normal or obese) and prevalence and degree of obesity in adulthood. There was a highly significant relation between the body weights in 1968-69 and 1974-75, while a low order negative correlation was found between body weight in 1968-69 and change in weight between 1968-69 and 1974-75. There was a significant relation between fat cell weight and weight index in the lower range and between fat cell number and weight index throughout the whole range studied. Body cell mass correlated with weight index and total fat cell number but not with fat cell weight. There was no significant correlation between body cell mass and obesity in childhood. There was a significant relation between degree of obesity and total fat cell number when age of onset was kept constant, but not between age of onset and total fat cell number when degree of obesity was kept constant. An association between childhood obesity and obesity in adulthood was shown. However, the concept of a critical period in childhood for changes in total fat cell number was not supported.

Adipose Tissue↗
PubMed1979

Effect of cardioselective and non-selective beta-blockade on the hypoglycaemic response in insulin-dependent diabetics.

The response to intravenous insulin was studied in seven diabetics after a dose of placebo, propranolol (40 mg), or metoprolol (50 mg). Two of the seven subjects also had a week's course of each of the same agents taken three times daily. Neither of the beta-blockers potentiated the effect of insulin as judged by the rate of reduction in blood-glucose. However, blood-glucose recovery was reduced significantly by propranolol, but not significantly by metoprolol. Propranolol caused severe bradycardia and raised diastolic blood-pressure during hypoglycaemia; these effects were milder with metoprolol. Propranolol inhibited the free-fatty-acid levels after hypoglycaemia to a greater extent than did metoprolol. The results strongly suggest that propranolol (and presumably other non-selective beta-blockers) is hazardous in subjects prone to hypoglycaemia. When diabetics require beta-blockade a cardioselective beta 1-blocker should be used.

Adult↗
PubMed1979

Human adipose tissue in culture. VIII. Studies on the insulin-antagonistic effect of glucocorticoids.

Biopsies of human adipose tissue were maintained for 1 wk in vitro with physiologic (1.5-30 X 10(-8) M) or pharmacologic (300 X 10(-8) M) concentrations of hydrocortisone or 1000 muU/ml insulin, or both. After this period, the explants were washed and incubated for 2 hr according to techniques generally used to study fat cell metabolism. Physiologic concentrations of hydrocortisone mainly exert an insulin antagonistic effect. Thus, the long-term effects of insulin in increasing lipolysis, as well as glucose metabolism to triglycerides, were reduced, as were the acute effects of insulin on these parameters. At these concentrations, the glucocorticoid itself did not influence the basal metabolic rates when due consideration was given to simultaneous changes in mean fat cell size. At higher concentrations, which may easily be reached during nonspecific glucocorticoid therapy, the glucose metabolism was reduced. Hydrocortisone decreased the number of insulin receptors. However, this cannot solely explain the insulin-antagonistic effect, since it was not overcome by a supramaximal concentration of insulin. Insulin and hydrocortisone together increased the lipoprotein lipase (lpl) activity several times. The resultant changes in LPL appear to depend upon the insulincorticosteroid ratio.

Adipose Tissue↗
PubMed1979

Differences in metabolic responses to beta-adrenergic stimulation after propranolol or metoprolol administration.

Isoprenaline, or the beta 2-agonist terbutaline, was infused in healthy male volunteers and the plasma levels of insulin, glucose and free fatty acids (FFA) were determined. Saline, propranolol, or the selective beta 1-receptor antagonist, metoprolol, was administered i.v. prior to the infusion of the beta-stimulants. The two beta-receptor blockers inhibited isoprenaline-induced increase in chronotropy to about the same extent, while the effects on systolic and diastolic blood pressure were in accordance with a selective beta1-blocking effect of metoprolol and a non-selective beta-blocking action of propranolol. Quantitative differences were found between metoprolol and propranolol on the metabolic parameters. The effects can best be described in terms of beta 1- or beta 2-receptors, where effects on plasma FFA and glycerol levels seem to be mainly beta1-mediated. An apparent beta 2-mediated effect was found for insulin release and hepatic glucose output.

Adult↗
PubMed1979

Quantitation of different cells in the epididymal fat pad of the rat.

To determine the number of adipocytes and cells developing into adipocytes (preadipocytes) in the epididymal fat pad of normal Sprague-Dawley rats, two methods were developed. Liberation of all cells from the tissue was obtained by a combination of lytic enzymes and mechanical treatment with only a limited loss of cell integrity; with large tissue masses, an initial perfusion was necessary. These cells were cultured in medium 199 supplemented with serum, glucose, insulin, a triglyceride emulsion, and methyl cellulose to form a culture medium with high viscosity in which it has been shown that the cells do no multiply. In this medium some of the cells developed into adipocytes and could be recognized and counted. The results show that there are about twice as many preadipocytes as mature adipocytes in the smallest rats examined (about 50 g). With increasing weight and age the mature adipocytes increased while the number of preadipocytes seemed to be constant up to a weight of about 150 g, after which they continuously diminished and could not be found in rats weighing more than 300 g. Here the number of mature fat cells had reached a constant level. These results are consistent with the formation of new preadipocytes up to a rat weight of about 150 g. In normal rats these cells successively fill up with triglyceride and disappear at a body weight of about 300 g when they have been transformed into mature adipocytes. The results are also consistent with the concept that no new adipocytes are formed spontaneously in the adult Sprague-Dawley rat. It was shown, however, that in media without methyl cellulose, isobutylmethylxanthine probably could induce the formation of new adipocytes in the cells isolated from all rats, including the heaviest (oldest). This finding shows that the potential of cells to develop into adipocytes also seems to exist in the adult rat under certain circumstances.

Adipose Tissue↗
PubMed1979

Metabolic studies in a case of Werner's syndrome.

A case of Werner's syndrome was investigated with regard to the immune system and peripheral insulin sensitivity. Routine immunological screening revealed no abnormality in either humoral or cell-mediated immune response. Intravenous glucose tolerance test showed a reduced glucose tolerance coupled with very high insulin levels. There was no evidence for increased levels of antagonistic hormones e.g., corticosteroids, growth hormone or thyroid hormones. Serum insulin binding capacity was normal. Adipose tissue metabolism revealed a reduced sensitivity to the effects of insulin both on glucose metabolism and on the antilipolytic effect. This was purely due to a shift in the dose-response curve to the right since maximal effects were the same as those found in control subjects. This reduced insulin sensitivity seems to be due to a reduction in the number of cellular insulin receptors.

Adipose Tissue↗
PubMed1979

Adipose tissue cellularity--metabolic aspects. The population study of women in Göteborg 1974-1975.

A representative population sample of middle-aged women was studied in 1974-75. In a subsample, body composition and adipose tissue cellularity variables were determined and individuals with a particular clinical disorder were compared with the total subsample. Women with diabetes mellitus had more body fat and higher fat cell weights and larger fat cell members, whereas these variables did not differ in women with IHD or hypertension compared with the total subsample. Total body fat correlated with arterial BPs, fasting blood glucose, serum lipids and serum uric acid. The correlations were stronger than those reported previously by us between weight index and these variables. In univariate analyses, fat cell weight correlated with systolic BP, serum triglycerides and serum uric acid, and fat cell number with diastolic BP, fasting blood glucose and serum uric acid. In multivariate analyses, when due allowance was made for total body fat, the correlations between these variables and fat cell weight or fat cell number did not reach statistical significance.

Adipose Tissue↗
PubMed1978

Adipose tissue cellularity in obese school girls before and after dietary treatment.

Mean fat cell size and adipose tissue cellularity were studied in 18 grossly obese girls and 17 age-matched reference girls. The obese girls had a combined hypertrophic-hyperplastic obesity with increments in fat cell size as well as in fat cell number. High insulin levels were found in the obese girls and the levels correlated with fat cell size. The obese girls had higher serum triglyceride levels than the reference group but the cholesterol levels were similar. After dietary treatment and advice for increased physical activity of the obese group, both groups were re-investigated with respect to adipose tissue cellularity after 1.5 to 1.9 years. Fat cell number was unchanged in the reference group while the obese girls in spite of treatment increased their cell number significantly. The obese girls who were most successfully treated had the lowest increase in fat cell number. The results suggest that treatment of childhood obesity may be of importance for the prevention of obesity later in life.

Adipose Tissue↗