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Biomedical subjects

P Arner

Publications and source records attributed to P Arner.

At least 271 records · Page 15Linked to original sources
PubMed1981

Changes in the effects of insulin on human adipose tissue metabolism in hyperthyroidism.

The in vitro effects of insulin on glycerol release and glucose incorporation into neutral lipids (lipogenesis) were studied in segments of sc adipose tissue obtained from 9 control subjects and 11 patients with hyperthyroidism; 6 patients were reinvestigated after treatment. In untreated hyperthyroidism, there was a decreased sensitivity to the antilipolytic effect of insulin, since the dose-response curve was shifted to the right; 250 microU/ml insulin were required for 50% of the maximal effect compared to 25 microU/ml in the controls. During antithyroid therapy, the dose-response curve normalized. Insulin caused a 25% increase in lipogenesis in the untreated hyperthyroid patients, but no consistent effect was seen in the control subject or in hyperthyroid patients during treatment.

Adipose Tissue↗
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

Thyroid hormone regulation of the catecholamine effects in human adipose tissue.

The possibility of a relationship between the thyroid hormone level and the peripheral action of catecholamines was examined in 4 normal-weight and 19 obese euthyroid subjects as well as in 27 hyperthyroid subjects by comparing the serum thyroid hormone level and the in vitro effect of catecholamines on lipolysis and cyclic AMP accumulation in adipose tissue incubated with and without isopropyl noradrenaline (ISNA) or noradrenaline (NA). ISNA- and NA-induced rates of lipolysis and cyclic AMP production were significantly correlated with free thyroxine index (r = 0.63-0.74) and with the serum triiodothyronine level (r = 0.83-0.87). The thyroid hormone level was neither correlated with basal rate of lipolysis nor with basal cyclic AMP production (r < 0.2). These results suggest that the magnitude of catecholamine-induced cyclic AMP production by peripheral cells may be regulated by the level of circulating thyroid hormones. The effect of thyroid hormones on lipolysis appears to be specifically linked to the action of catecholamines.

Adipose Tissue↗
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↗
PubMed1981

Sensitive kinetic bioluminescent assay of glycerol release from human fat cells.

A sensitive and accurate assay of lipolysis has been developed, measuring the rate of glycerol release from fat cells with a bioluminescent assay. The rate of glycerol-dependent ATP-consumption in a system consisting of glycerokinase, ATP, luciferin, and luciferase was determined kinetically as a decrease of the ATP-induced luminescence and used for calculation of the concentration of glycerol. Under the conditions employed, it was possible to measure the concentration of glycerol down to a level of about 0.5 micron mol/l. Under the same conditions, the detection limit of the usual fluorometric method was about 15 micron mol/l. The coefficient of variation obtained with the bioluminescent assay was 11% at a level of 1.0 micron mol of glycerol, 2-6% at a level of about 5 micron mol/l, and 1-3% at a level of about 20 micron mol/l. Satisfactory results were obtained in different recovery experiments. Using human fat cells, it was possible to determine the rate of glycerol release with a cell concentration in the medium of only 5,000-10,000 cells/ml. It is concluded that the bioluminescent assay of glycerol release should be preferred when there is a demand for sensitivity, e.g., when the rate of lipolysis is low and when only a small amount of biopsy material is available.

Adipose Tissue↗
PubMed1980

Plasma C-peptide and serum insulin antibodies in diabetic patients receiving pancreatic transplants.

Plasma C-peptide and serum insulin antibody levels were determined in 5 diabetic patients undergoing vascularized pancreatic transplantation. The grafts functioned well at first and exogenous insulin could be withdrawn, but one to 7 weeks later the grafts were rejected. After the transplantation there was an increase in the fasting plasma C-peptide level, and B-cell stimulation with glucose or glucagon evoked a C-peptide response. Healing of ischaemic damage was reflected in an increase in the C-peptide level. During graft rejection the C-peptide level fell. Measurement of plasma C-peptide levels provides a direct index of the B-cell function of the pancreatic graft. After transplantation the insulin antibody level fell exponentially, with an apparent half life of 10-11 days, whereas the level of total IgG was variable. The results indicate that formation of insulin antibodies ceases immediately on removal of the immunogenic stimulus, that is, on withdrawal of xenogeneic insulin.

Adult↗
PubMed1980

Importance of the cyclic AMP concentration for the rate of lipolysis in human adipose tissue.

1. The activation of lipolysis on incubation of human subcutaneous adipose tissue was examined in terms of the relationship between the release of glycerol and the concentration of tissue cyclic AMP. 2. A strong positive correlation was obtained between the maximum concentration of cyclic AMP and the rate of glycerol release in the presence of noradrenaline (r = 0.9), whereas, in the basal state, these two parameters were only weakly correlated (r = 0.45). 3. It appears that the noradrenaline-induced rate of lipolysis depends upon the maximal concentration of cyclic AMP that is present in human adipose tissue.

Adipose Tissue↗
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↗
PubMed1980

Experience with pancreatic transplantation in Stockholm.

Eight attempts at segmental pancreatic transplantation were made in 6 diabetic patients. While the indications for transplantation differed all the patients were severely incapacitated by the disease. None was uremic. The body and tail of the pancreas from cadaveric donors was used, the grafts were revascularized to the recipient's iliac vessles. Six of the grafts provided control of blood glucose for 7-51 days. Five of the grafts then failed owing to rejection, and one had to be removed while still functioning, because of arterial bleeding. Important lessons have been learned concerning both surgical and immunological aspects of this form of treatment : 1) Ducto-jejunostomy should be used to provide exocrine pancreatic drainage. 2) HLA-DR typing for donor-recipient selection and thoracic-duct drainage as an adjunctive immunosuppressive measure should be used to reduce the incidence of graft rejection. 3) An elevation of the postprandial blood glucose concentration is a first sign of rejection and should cause treatment. 4) Graft rejection can be reversed by conventional steroid medication.

Adult↗
PubMed1980

Segmental pancreatic transplantation with duct ligation or drainage to a jejunal Roux-en-Y loop in nonuremic diabetic patients.

The results of seven segmental pancreas transplantations in diabetic patients, using a jejunal Roux-en-Y loop for drainage of digestive enzymes, are presented. An initial case with pancreatic duct ligation is also included. The patients ranged in age from 30 to 45 yr, with duration of diabetes from 8 to 24 yr, and were incapacitated but not uremic. Immunosuppression was attempted with azathioprine, prednisone, and antilymphocyte globulin, and, in one patient, thoracic duct drainage was added. The pancreas tolerated at least 16 min of warm ischemia and at least 4 h of cold storage; flushing with a balanced electrolyte solution was optimal. Six of the grafts provided control of blood glucose for 7--51 days, and, in one patient, an intravenous glucose tolerance test was normal at 7 and 21 days. Five of the grafts failed due to rejection 7--51 days after transplantation, and one was removed at 14 days, while still functioning, due to bleeding. In one case, early detection of rejection by a rise in post-prandial blood glucose was treated and reversed by corticosteroid administration. Two failed in the immediate postoperative period from vascular thrombosis. Drainage of pancreatic secretions from a fistula was a common problem.

Adult↗
PubMed1980

Influence of adipocyte isolation by collagenase on phosphodiesterase activity and lipolysis in man.

The maximum phosphodiesterase activity (Vmax) with low and high Km was, respectively, 10- and 3-times greater in tissue fragments than in collagenase-isolated adipocytes obtained from subcutaneous fat layers in man. The exposure of such tissue fragments to collagenase of various origins in order to isolate the fat cells resulted in a 60-70% inhibition of phosphodiesterase (PDE) activity. Noradrenaline- and isopropyl noradrenaline-induced rates of lipolysis were more rapid in the isolated fat cells than in the tissue fragments. The sensitivity to catecholamines, however, was the same for the two tissue preparations. Nor did they differ in respect to the effect of theophylline, a PDE inhibitor, on the rate of lipolysis. The time curve for cyclic AMP accumulation was significantly higher in the isolated adipocytes than in tissue fragments in the presence of isopropyl noradrenaline. It is concluded that the greater lipolytic response of collagenase-isolated adipocytes than of tissue fragments to catecholamines may be attributed, at least in some measure, to the higher concentration of cyclic AMP resulting from a decrease in PDE activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1979

Relationship between lipolysis, cyclic AMP, and fat-cell size in human adipose tissue during fasting and in diabetes mellitus.

The in vitro relationship between fat-cell size, glycerol release, and peak concentration of cyclic AMP was investigated in human adipose tissue obtained from 25 obese nondiabetic patients before and after a 7-day fast and from 23 patients with untreated diabetes mellitus. In the obese nondiabetic patients there was a linear correlation between fat-cell size and cyclic AMP concentration, and fat-cell size and the rate of lipolysis. This was found both in nonfasting and fasting nondiabetic patients. However, in diabetes mellitus, there was only a relationship between cell size and cyclic AMP concentration. The alpha-adrenergic and beta-adrenergic activity in human adipose tissue was assessed by comparing the effect of isoprenaline and noradrenaline on the cyclic AMP concentration. The activity of both receptors was found to be increased in fasting obese patients and in diabetics. In both conditions the alpha-adrenergic response to catecholamines predominated in small fat cells, whereas in large ones the beta response predominated. The results suggest that during fasting and in diabetes mellitus there is a correlation between fat-cell size and the responsiveness of the adrenergic receptors. Thus, catecholamines may be involved in regulating the fat-cell volume. The view is expressed that the abnormal catecholamine-induced lipolysis is solely due to changes at the level of the adrenergic receptors during fasting, whereas in diabetes mellitus the sequentional activation of lipolysis is disturbed at deeper sites as well.

Adipose Tissue↗
PubMed1979

Regional differences in the control of lipolysis in human adipose tissue.

Omental fat cells were 30% smaller than those in subcutaneous regions. In omental fat cells with a mean diameter of 95 mu, the basal cAMP concentration was 50% lower, but the basal rate of glycerol release was three times as rapid as in subcutaneous (epigastric) fat cells of identical size. Added at maximal effective concentration, noradrenaline increased the level of cAMP and the rate of glycerol release more markedly in the omental than in the subcutaneous adipocytes, whereas the response to isopropyl noradrenaline was similar. Before starvation the lipolytic effects of noradrenaline and isopropyl noradrenaline, respectively, were identical in the two regions of subcutaneous adipose tissue investigated (femoral and hypogastric). The findings were well related to the tissue levels of cAMP induced by the two agents. During starvation noradrenaline and isopropyl noradrenaline increased the cAMP level and the rate of lipolysis in fat cells obtained from the hypogastric region, whereas noradrenaline decreased these parameters in femoral adipocytes. Starvation was associated with a more prominent inhibitory effect of phenylephrine on basal and isopropyl-noradrenaline-induced lipolysis in femoral than in hypogastric adipose tissue. In conclusion, differences exist between different regions of adipose tissue in their lipolytic responsiveness to noradrenaline, which seems related to the balance between alpha- and beta-adrenergic receptor response.

Adipose Tissue↗
PubMed1979

Regulation of lipolysis by human adipose tissue in hyperthyroidism.

The effects of noradrenaline (NA) and isopropyl-noradrenaline (ISNA) on glycerol release and cAMP levels in sc adipose tissue were studied in vitro in 27 patients with hyperthyroidism. In 11 patients, the studies were repeated after 6--12 months of treatment for hyperthyroidism. A third group comprised 21 euthyroid patients otherwise healthy except for morbid obesity. The lipolytic response to ISNA, observed in untreated thyrotoxic patients, was found to be reduced by 30% when the patients were reexamined after treatment for thyrotoxicosis. This reduction was attributable to a decrease in the cAMP level. This was observed whether adipose tissue was incubated in the presence or absence of a phosphodiesterase inhibitor, theophylline. Both NA and ISNA induced 50% more rapid glycerol release and 4 times higher cAMP levels in adipose tissue of the thyrotoxic subjects than in the obese euthyroid patients. A positive correlation between tissue cAMP and glycerol release, on one hand, and mean fat cell size, on the other hand, was observed in treated thyrotoxic patients and obese euthyroid patients but was not recorded in the untreated hyperthyroid patients. The basal rate of lipolysis was not altered in thyrotoxicosis. The results suggest that the enhanced lipolytic response to catecholamines in adipose tissue of hyperthyroid patients is due to increased beta-adrenergic responsiveness. In addition, a disruption in subsequent stages of the regulatory pathway at the level of protein kinase or hormone-sensitive lipase also seems possible.

Adipose Tissue↗