Biomedical subjects

P Engfeldt

Publications and source records attributed to P Engfeldt.

At least 55 records · Page 3Linked to original sources

PubMed1984

Influence of fasting on lipolytic response to adrenergic agonists and on adrenergic receptors in subcutaneous adipocytes.

The influence of 1 week's total fasting on the lipolytic effect of adrenergic agonists and on the binding of adrenergic antagonists was examined in isolated adipocytes of subcutaneous specimens removed from the hypogastric and the femoral sites in seventeen obese women. In the femoral adipocytes the lipolytic sensitivity to isopropyl noradrenaline decreased 30-fold (P less than 0.01) during fasting. The specific binding of the radioligands (-)-[3H]-dihydroalprenolol and (-)-[125I]-cyanopindolol decreased significantly during fasting, essentially owing to a reduction in the receptor density. In adipocytes from the hypogastric region no such changes were found. For both tissue regions fasting induced a right-ward shift in the dose-response curve for the inhibitory effect of the alpha 2 agonist, clonidine, on theophylline-induced lipolysis, corresponding to a 10-fold decrease in sensitivity. There was also a significant decrease of about 20% in the alpha 2-adrenoceptor density, as estimated with the radioligand [3H]-yohimbine. The results suggest that the regulation of the lipid mobilization in man by the sympathetic nervous system during fasting occurs not only through an increase in the level of circulating noradrenaline but also through changes in the adrenergic receptor density of the adipocytes.

Adipose Tissue↗

PubMed1984

Influence of obesity on the antilipolytic effect of insulin in isolated human fat cells obtained before and after glucose ingestion.

The antilipolytic effect of insulin was studied in 9 obese and 10 age- and sex-matched subjects of normal weight. Isolated fat cells were taken before and 1 h after an 100 g oral glucose load. Insulin inhibition of basal and isoprenaline-induced rates of lipolysis were determined by using a sensitive bioluminescent glycerol assay. When compared with the controls, the obese group showed a lower glucose tolerance, a higher insulin secretion, and a lower specific insulin receptor binding per adipocyte surface area, which would suggest an insulin-resistant state. Before oral glucose, however, the sensitivity of the antilipolytic effect of insulin was enhanced 10-fold in obesity (P less than 0.01), but the maximum antilipolytic effect was not altered. Glucose ingestion induced a 10-25-fold increase in insulin sensitivity (P less than 0.01) and a 10% but not significant increase in specific adipocyte insulin receptor binding in the nonobese group. In the obese group, however, neither the insulin binding nor the antilipolytic effect of the hormone was increased by oral glucose. After oral glucose, insulin sensitivity was similar in the two groups. The concentration of the hormone which produced a half maximum effect was about 1 microU/ml. Similar results were obtained with insulin inhibition of basal and isoprenaline-stimulated glycerol release. It is concluded that, after an overnight fast, the sensitivity of the antilipolytic effect of insulin is markedly enhanced in adipocytes of "insulin-glucose resistant" obese subjects, presumably because of alterations at postreceptor levels of insulin action. In obesity, the antilipolytic effect of insulin seems normal after glucose ingestion. Furthermore, in adipocytes of subjects of normal weight, oral glucose rapidly stimulates the sensitivity of the antilipolytic effect of insulin, apparently because of changes at postreceptor sites. This short-term regulation of insulin action following the ingestion of glucose does not seem to be present in obesity.

Adipose Tissue↗

PubMed1984

Insulin secretion in human obesity: effects of prolonged fasting and refeeding.

The effects of prolonged fasting and refeeding on insulin secretion were examined in seven obese non-diabetic subjects. Plasma insulin and C-peptide concentrations were measured before and after fasting for 7 days, and after refeeding with a low caloric diet. Urine C-peptide excretion during 24 h was determined daily during the study period. Plasma insulin and C-peptide levels fell by about 50 percent during fasting and returned to the prefasting values after refeeding. During fasting the 24-h urine C-peptide excretion was markedly diminished; after 7 days it was less than 10 percent of the prefasting level; on refeeding a low caloric diet, it increased significantly although not to the initial basal values. It is concluded that in human obesity pancreatic insulin secretion is markedly diminished by prolonged fasting.

Adult↗

PubMed1983

Determination of adrenoceptors of the alpha 2-subtype on isolated human fat cells.

Binding state for the selective alpha 2-adrenergic antagonist (3H)-yohimbine on isolated intact human subcutaneous abdominal fat cells is described in the present study. Specific binding was rapid, reversible, saturable and stereospecific. Adrenergic antagonists competed with (3H)-yohimbine binding in the order indicative of alpha-receptors. Competition studies with adrenergic antagonists revealed that (3H)-yohimbine binding sites displayed properties consistent with those of alpha 2-subtype. Saturation experiments demonstrated that (3H)-yohimbine specific binding was of high affinity with a dissociation constant (Kd) of 3.7 +/- 0.4 nmol/l and a maximum occupancy (BO) of 10.5 +/- 2.1 pmol/10(7) cells. The latter corresponded to approximately 600,000 alpha 2-receptors/fat cell. A significant (P less than 0.002) linear relationship was found between the fat cell volume and BO. A complete saturation experiment for the determination of Kd and BO could be performed using 0.5 g adipose tissue (0.5 ml isolated fat cells), which is 30 times less required when adipocyte membranes are used for these studies. It is concluded that the method can be used for the study of alpha 2-receptor properties and regulation in subcutaneous adipose tissue in a given individual.

Adipose Tissue↗

PubMed1983

Studies on the regulation of phosphodiesterase in human adipose tissue in vitro.

The influence of several agents known to affect the rate of lipolysis or the phosphodiesterase (PDE) activity in rat adipose tissue was studied in human adipose tissue in vitro. Only insulin, catecholamines, prostaglandin E1, and cAMP increased PDE activity in man (by 20-40% over the control values). In dose-response studies, it was found that the ED50 values for insulin and isopropyl noradrenaline were of the same magnitude as the previously observed ED50 values for lipolysis in human adipose tissue. The time course for insulin and isopropyl noradrenaline showed maximum stimulation after 10 min, followed by a decline, with the curve approaching zero at 60 min. In subcellular fractions of adipose tissue, the highest specific PDE activity was found in the particulate fraction, in which the effects of both insulin and isopropyl noradrenaline were most marked. It is concluded that the stimulatory effect of catecholamines on PDE may be one reason for the failure of these agents to produce a sustained increase in the cAMP level and that the effect of insulin on PDE may be one mechanism by which insulin reduces the rate of lipolysis.

Adipose Tissue↗

PubMed1983

Site differences in insulin receptor binding and insulin action in subcutaneous fat of obese females.

Regional differences in insulin-induced sc adipose tissue metabolism in 7 weight-stable obese women were investigated. Insulin receptor binding to isolated fat cells and the effects of insulin on glucose oxidation and lipolysis in adipose tissue segments obtained from abdominal and femoral regions were determined. The mean dose-response relationships for the antilipolytic effect of insulin were almost identical in both regions; the half-maximum effect (ED50) was obtained with 100 microU/ml, and the maximum effect (responsiveness) was a decrease of about 7 mumol glycerol/10(7) cells X 2 h. The mean insulin dose-response curves for glucose oxidation differed; the ED50 was 100 microU/ml in femoral and 300 microU/ml in abdominal adipose tissue (P less than 0.01), and responsiveness was enhanced 2-fold in femoral fat (P less than 0.01). Insulin receptor number was higher in femoral than in abdominal adipocytes (600,000 and 250,000 sites/cell, respectively; P less than 0.01). However, the apparent insulin receptor affinity was increased 2- to 3-fold in abdominal fat cells. The ED50 for insulin stimulation of glucose utilization occurred at a higher level of receptor occupancy in abdominal than in femoral fat. Thus, significant regional differences in insulin binding and insulin action were found in sc fat depots in obese women. Differences at the postreceptor rather than at the receptor level are probably responsible for the enhanced insulin-induced glucose utilization in femoral fat.

Abdomen↗

PubMed1983

The relationship between the basal lipolytic and lipoprotein lipase activities in human adipose tissue.

The basal rate of lipolysis and basal lipoprotein lipase activity were determined in vitro in subcutaneous adipose tissue obtained from eight healthy non-obese subjects, ten obese subjects before and during one week's starvation, nine untreated non-insulin dependent diabetics and seven treated non-insulin dependent diabetics whose disease had been under metabolic control for at least three months. There was a negative correlation between the rate of lipolysis and activity of lipoprotein lipase in untreated diabetes mellitus and during starvation (r from -0.87 to -0.81). Under these two conditions the rate of lipolysis is increased and the lipoprotein lipase activity is decreased. There was no correlation between lipolysis and lipoprotein lipase in non-obese subjects, non-starving obese subjects and treated diabetic patients (r from 0.11 to 0.36). Thus, during starvation and in untreated diabetes, there is a strong reciprocal relationship between basal lipolytic activity and basal lipoprotein lipase activity in human adipose tissue which is not found under normal conditions or in obesity and well-controlled diabetes. It is concluded that a negative connection between lipolysis and lipoprotein lipase in human adipose tissue may be of physiological importance for the regulation of the energy balance in conditions such as untreated non-insulin dependent diabetes and starvation where adipose tissue lipids are the major source of energy.

Adipose Tissue↗

PubMed1982

Changes in phosphodiesterase activity of human subcutaneous adipose tissue during starvation.

The phosphodiesterase (PDE) activity, the basal rate of lipolysis and the basal cyclic AMP level in adipose tissue were determined in hypogastric and gluteal specimens obtained from 14 obese healthy subjects before and after one week of starvation. During starvation there was a significant increase in both the tissue level of cyclic AMP and the rate of lipolysis, whereas the apparent values of Vmax of the low and high Km forms of PDE decreased significantly-i.e. by about 50 and 30 percent. respectively. The substrate concentration of cyclic AMP at Vmax of the low Km PDE corresponded to the tissue level of the nucleotide. During, but not before, starvation there was a positive correlation between Vmax of the low Km PDE and the cyclic AMP level (r = 0.7-0.8). The metabolism in the tissues from the two fat depots exhibited similar variations during starvation. The findings suggest that the low Km form of PDE is inhibited during starvation. This may be one factor responsible for the starvation-mediated increase in the cyclic AMP levels and the rate of lipolysis in adipose tissue.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1982

Phosphodiesterase activity in human subcutaneous adipose tissue in hyper- and hypothyroidism.

Phosphodiesterase (PDE) activity was determined in sc adipose tissue from 12 patients with untreated hyperthyroidism, 8 patients with untreated hypothyroidism, and 10 healthy nonobese subjects. Eight of the hyperthyroid group were reexamined after treatment when they were euthyroid. The apparent Vmax of the low Km form of PDE was 25% lower in untreated hyperthyroidism (P less than 0.05) and 100% higher in untreated hypothyroidism (P less than 0.01) than in the controls; treatment of the hyperthyroidism resulted in normalization of the value. There was a positive correlation between the mean fat cell volume and the Vmax of the low Km PDE in all conditions (r = 0.64-0.85). As regards the high Km form of PDE, the Vmax values for both hyper- and hypothyroid patients did not differ from those for the control group. The results of this study suggest that in man, the apparent Vmax for the PDE with low Km is determined by the thyroid hormones.

Adipose Tissue↗

PubMed1982

Phosphodiesterase activity in human subcutaneous adipose tissue in insulin- and noninsulin-dependent diabetes mellitus.

The influence of diabetes mellitus on phosphodiesterase (PDE) activity in human sc adipose tissue was investigated in 8 patients with insulin-dependent (IDDM) and 9 with noninsulin-dependent (NIDDM) diabetes mellitus. The results were compared with data from 10 healthy normal weight subjects. The apparent maximal PDE activity (Vmax) of the low Km form of PDE was 60% lower (P less than 0.01) in untreated IDDM and NIDDM than in the control state. After treatment of IDDM and NIDDM, the Vmax of the low Km PDE was normalized. In untreated IDDM and NIDDM, the Vmax of the low Km PDE was correlated to the cAMP level (r = 0.8). This correlation was not observed after antidiabetic treatment or in the control state. The apparent Vmax values of the high Km form of PDE were similar in the diabetic states and in control subjects. The results suggest that the low Km PDE is inhibited in untreated IDDM and NIDDM. In these conditions, PDE may be one factor responsible for regulation of the cAMP level.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1982

An assay for beta-adrenergic receptors in isolated human fat cells.

The beta-adrenergic receptors have been characterized in isolated human adipocytes using a potent beta-adrenergic antagonist (-)-[3H]dihydroalprenolol. Binding of (-)-[3H]dihydroalprenolol to isolated fat cells was stereospecific and saturable, the maximum number of binding sites calculated being 7.8 +/- 2.2 pmol of bound ligand/10(7) cells, corresponding to 450,000 binding sites/cell. The dissociation constant was estimated to be 2.7 +/- 1.1 nM. The results with competition-inhibition experiments using beta-adrenergic agonists and antagonists indicated that the binding sites in isolated adipocytes were predominantly of the beta1-subtype; about 80% of the receptors were of this type. With the present method, specific beta-adrenergic receptor number and affinity in isolated human adipocytes could be determined in about 1 g of human adipose tissue.

Adipose Tissue↗

PubMed1982

Changes in the metabolism of fatty acids in adipose tissue in obese patients with primary hypertriacylglycerolemia.

Changes in the release and esterification of free fatty acids (FFA) in adipose tissue were looked for as a cause of moderate primary hypertriacylglycerolemia (HTG) in five obese subjects. Comparison was made with six obese normolipidemic subjects. The two groups were matched for body weight, tolerance of intravenous glucose, fat cell size, fasting levels of serum immunoreactive insulin, and serum insulin response to an intravenous glucose load. Subcutaneous adipose tissue was incubated in vitro with [1-14C]palmitic acid for 30, 60, and 120 min. There was a significant, twofold increase in the rate of FFA mobilization, but no change of glycerol release in HTG patients. The adipose tissue levels of mono- and diacylglycerols were similar in the two groups of subjects and did not change during incubation. Re-esterification of FFA, calculated from the net changes in medium and in tissue FFA and glycerol release, was lower in HTG patients than in the controls (3 and 12 mumol/10(7) cells/hr, respectively; P less than 0.025). In adipose tissue of HTG patients, the amount of radioactive fatty acids incorporated into triacylglycerols (TG) was 50% lower (P less than 0.025), whereas that incorporated into tissue FFA was three times higher (P less than 0.01) when compared with control patients. It is concluded that, in adipose tissue of obese patients with primary hypertriacylglycerolemia, the esterification of free fatty acids to triacylglycerol is decreased. As a consequence, free fatty acids are mobilized at an increased rate.

Adipose Tissue↗

PubMed1981

The antilipolytic effect of insulin in human adipose tissue in obesity, diabetes mellitus, hyperinsulinemia, and starvation.

The antilipolytic effect of insulin in vitro was investigated in conditions known to be associated with resistance to the effect of insulin on glucose metabolism. Human subcutaneous adipose tissue was obtained from 14 obese subjects before and during starvation for 7 days, 12 untreated non-insulin dependent diabetics (NIDDM), 6 untreated insulin dependent diabetics (IDDM), and 10 nonobese control subjects. The tissue was incubated with and without insulin in concentration ranging from 1-10,000 microunits/ml. Responsiveness (maximum effect) and sensitivity to insulin were determined under basal induction conditions, since insulin had a bimodal effect on noradrenaline stimulated lipolysis. Under normal conditions both insulin sensitivity and insulin responsiveness were positively correlated with the basal rate of lipolysis. In obesity, IDDM and NIDDM there were no change in insulin sensitivity or in insulin responsiveness. When the obese subjects were divided into one hyperinsulinemic group (6 individuals) and one group with normal fasting serum insulin levels (7 individuals) a similar antilipolytic effect of insulin was observed in the two groups. During starvation there was a 20-fold increase in insulin sensitivity (p less than 0.01) but no change in insulin responsiveness in femoral fat and only a decrease in responsiveness (p less than 0.01) in abdominal fat. The present data supports the view that antilipolysis in human fat cells is not involved in the insulin resistance seen in obesity, starvation, diabetes and hyperinsulinemia.

Adipose Tissue↗

PubMed1981

Post receptor activation of lipolysis in starvation, diabetes mellitus and hyperthyroidism.

Activation of lipolysis by cyclic AMP in conditions with accelerated lipid mobilization was examined in subcutaneous adipose tissue incubated in vitro. In (a) 16 obese patients before and during therapeutic starvation, (b) 18 diabetics before and after antidiabetic treatment and (c) 11 hyperthyroid patients before and after anti-thyroid treatment, a positive correlation was found between stimulation of basal cyclic AMP accumulation and stimulation of basal glycerol release using either isopropyl noradrenaline or noradrenaline (r = 0.6-0.9). During antidiabetic treatment stimulation of lipolysis increased in relation to that of cyclic AMP accumulation (F = 10.1, p less than 0.01), whereas during antithyroid therapy there was a decrease (F = 95.2, p less than 0.01). Starvation did not alter the relationship between lipolysis and cyclic AMP in hypogastric adipose tissue whereas in femoral tissue stimulation of lipolysis decreased in relation to that of cyclic AMP accumulation (F = 9.6, p less than 0.01). It is concluded that the amount of cyclic AMP needed to promote lipolysis is increased during starvation and in diabetes mellitus but is decreased in hyperthyroidism. From the studies during starvation it appears that regional differences in the post-receptor activation of lipolysis exist in human adipose tissue.

Adult↗

PubMed1981

Site differences in the basal metabolism of subcutaneous fat in obese women.

The basal capacity of femoral and abdominal fat to hydrolyze and store acylglycerols was investigated in obese women before and during 1 week of fasting. Before fasting, the lipolytic activity was lower and the lipoprotein lipase activity higher in femoral than in abdominal fat. During fasting, femoral fat lipoprotein lipase activity decreased and lipolytic activity increased to levels similar to those in abdominal fat. Acylglycerol syntheses were similar in the two fat depots before fasting, but decreased to a lower level at the abdominal than at the femoral site during fasting. Fat cell size decreased in the abdominal but not in the femoral site during fasting. Thus, regional variations in storage and mobilization of fat were found both in the fed and fasted states.

Abdomen↗

PubMed1981

In vivo observations on the lipolytic effect of noradrenaline during therapeutic fasting.

To assess the influence of fasting on the lipolytic effect of catecholamines in vivo noradrenaline (NA) was infused to 15 obese subjects before and after 7 days of fasting. The infusion of 7.5 microgram/min NA for 10 min was associated with a greater lipolytic response during than before fasting, as judged from changes in the plasma FFA and glycerol levels. The hemodynamic effects of NA were similar in both conditions. NA sensitivity was tested by infusing the hormone at an increasing rate from 0.05-2 microgram/min. During fasting, there was a 10-fold increase in the sensitivity to the lipolytic effect of NA, and the NA infusion significantly reduced the mean serum insulin level. Before fasting, the insulin level was constant during NA infusion. The increments in the plasma NA concentration were similar in both conditions. When insulin was infused at a constant rate, and graded NA doses were infused simultaneously, no lipolytic effect of NA at rates of 1 and 2 microgram/min significantly increased the plasma glycerol level. Thus, fasting enhances the lipolytic effect of NA in vivo, and this effect is due to increased sensitivity to NA and also to NA-induced depression of the circulating insulin level.

Adult↗

PubMed1981

Regulation of lipolysis in hyperthyroidism.

The investigation (Fig. 1) clearly shows that the ability of isoprenaline in particular and, to a less extent, of noradrenaline to increase the accumulation of cyclic AMP and thus also the rate of lipolysis is enhanced in hyperthyroidism. No evidence was found of changes in the sensitivity to either beta 1- or alpha -adrenergic agonists. Although further studies are needed, the findings supported the idea that the augmented cyclic AMP accumulation is due to changes below the receptor level. Second, a significant decrease was observed in the apparent Vmax of the PDE with apparent low Km. Third, metabolic disturbances closer to the lipolytic system may exist. Some indirect evidence for this hypothesis was the finding of relatively more rapid lipolysis in relation to the cyclic AMP level in hyperthyroidism. The investigations have raised a number of questions about the nature of the metabolic changes in hyperthyroidism. The findings suggest that there are multiple abnormalities, localized at different levels of mechanisms regulating lipid mobilization. Investigations of subcutaneous tissue fragments in man seem to offer good opportunities for exploring these abnormalities.

Adrenergic alpha-Agonists↗

PubMed1980

Blood glucose control and lipolysis in diabetes mellitus.

The relationship between the blood glucose level and the rate of lipolysis was investigated in 19 maturity onset diabetics (MOD) and 9 juvenile onset diabetics (JOD). Subcutaneous adipose tissue was incubated with and without isoprenaline or noradrenaline. Before antidiabetic treatment the blood glucose concentration was positively correlated with basal and catecholamine-induced rates of lipolysis in MOD (R = 0.41--0.60) and in JOD (r = 0.51--0.71). The reduction in blood glucose concentration during antidiabetic treatment was positively correlated with the reduction in the rate of lipolysis in MOD (r = 0.50--0.64) and in JOD (r = 0.75--0.90). Fat cell size and blood glucose level were not correlated either in untreated or treated diabetics. In diabetes mellitus, blood glucose homeostasis and rate of lipolysis in adipose tissue seem to be associated. The relationship is most apparent in JOD.

Adipose Tissue↗