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Biomedical subjects

J Ostman

Publications and source records attributed to J Ostman.

At least 181 records · Page 10Linked to original sources
PubMed1978

Relationship between the tissue level of cyclic AMP and the fat cell size of human adipose tissue.

The relationship between mean fat cell size, maximal tissue cyclic AMP concentration, and glycerol release was investigated in human subcutaneous adipose tissue incubated in vitro with or without isoprenaline or noradrenaline added at maximal effective concentrations. Basal and stimulated glycerol release and cyclic AMP concentration were each related to the fat cell size. Whether or not the phosphodiesterase inhibitor theophylline was present in the incubation system, basal and noradrenaline-induced cyclic AMP levels were significantly correlated with the fat cell size. The noradrenaline-induced cyclic AMP levels resulted in twice as rapid glycerol release as could be expected from the basal ratio between glycerol release and cyclic AMP. Furthermore, both basal and noradrenaline-induced glycerol release in relation to the cyclic AMP levels were more rapid in enlarge fat cells. It is concluded that basal and catecholamine-induced production of cyclic AMP is related to the fat cell size and that a quantitative relationship exists between rate of lipolysis and maximal tissue levels of cyclic AMP in human adipose tissue. Basal and noradrenaline-induced lipolysis are probably regulated by different mechanisms and the lipolytic sensitivity to cyclic AMP seems increased in large fat cells.

Adipose Tissue↗
PubMed1977

Monoamine metabolites in cerebrospinal fluid during treatment with clonidine or alprenolol.

Lumbar cerebrospinal fluid (CSF) concentrations of the major metabolites of noradrenaline (4-hydroxy-3-methoxyphenyl glycol, HMPG), serotonin (5-hydroxyindoleacetic acid) and dopamine (homovanillic acid) were measured before and during the administration of clonidine or alprenolol to hypertensive patients. The noradrenaline receptor stimulant clonidine significantly decreased the CSF level of HMPG, but there was no consistent change in the concentration of serotonin or dopamine metabolites. Patients on alprenolol showed no change in the levels of these metabolites in CSF.

Adult↗
PubMed1977

Differential inhibition of lipolysis in human adipose tissue by adrenergic beta receptor blocking drugs.

The effects of various adrenergic beta receptor agonists and antagonists on lipolysis (measured as glycerol release) in human adipose tissue in vitro were studied. Of the agonists investigated, the potency rank order was isoproteronol greater than norepinephrine greater than salbutamol. Adrenergic beta receptor blocking drugs inhibited catecholamineinduced lipolysis competitively. Propranolol was the overall most effective compound, followed by metoprolol, alprenolol and practolol, whereas butoxamine and H35/25 were weak inhibitors. The results indicate that the adrenergic reciptor mediating lipolysis in human adipose tissue is of type beta-1. Basal and theophylline-induced lipolysis was reduced when higher concentrations of these drug were used.

Adipose Tissue↗
PubMed1977

Steroid diabetes after renal transplantation--a preliminary report.

The incidence of steroid diabetes mellitus was studied retrospectively in 84 renal transplant recipients with grafts which had functioned longer than 3 months. The observation time ranged between 3 and 36 months (mean 17 months). Overt diabetes necessitating treatment was found in 24 patients (29%). Another 14 patients had transient elevations in blood glucose. The incidence of steroid diabetes was found to correlate with increasing age and body weight and with the number of rejection episodes. In the majority of the patients with manifest diabetes it was diagnosed within three months after transplantation.

Adolescent↗
PubMed1976

Pharmacokinetics and pharmacodynamics of alprenolol in the treatment of hypertension. II. Relationship to its effect on blood pressure and plasma renin activity.

The kinetics of alprenolol, in relation to its effect on blood pressure and plasma renin activity, have been studied in sixteen patients. A within-patient comparison was made between therapy for six weeks with placebo or alpronolol 200 mg thrice daily. Thirteen patients responded to alprenolol by a signoficant fall in blood pressure. In three other patients treatment did not lower blood pressure. In the group as a whole there was no significant correlation between the fall in systolic, diastolic or mean blood pressure, and the steady-state plasma alprenolol concentration, renin status, or degree of beta blockade. However, the thirteen responsive patients showed a significant relationship (p less than 0.05 - 0.001) between the log mean steady-state plasma alprenolol concentration and the hypotensive response.

Adult↗
PubMed1976

Plasma levels and effects of metoprolol on blood pressure, adrenergic beta receptor blockade, and plasma renin activity in essential hypertension.

The effects of metoprolol, a selective beta adrenergic receptor antagonist, on blood pressure, beta receptor blockade (antagoinst of isoproterenol and exercise tachycardia), and plasma renin activity (PRA) have been compared with those of placebo in 16 patients with essential hypertension. The dose of metroprolol was 25 mg three times daily for 1 wk and thereafter 100 mg three times daily for 5 wk. The mean decrease in blood pressure during treatment with metoprolol was 24 +/- 3.8 (SEM)/10 +/- 2.1 mm Hg in the lying position and 23 +/- 4.4/9 +/- 3.1 mm Hg after 1 min in the standing position. At a dose of 2.9 to 5.4 mg/kg, steady-state plasma concentrations of metoprolol varied 17-fold (from 20 to 341 ng/ml) between patients and correlated with the interindividual variability in isoproterenol antagonism (r = 0.58, p less than 0.05) and decrease in exercise tachycardia (r = 0.65, p less than 0.01). By contrast, neither of these variables correlated with the dose of metoprolol in mg/kg. Metoprolol decreased PRA by 67 +/- 1.9 and 71 +/- 1.2% in the lying and standing positions, respectively. The decrease in the mean arterial blood pressure in the lying position was significantly correlated to the PRA during the placebo period (r = 0.61, p less than 0.05) but not to the plasma steady-state levels of metoprolol, the degree of beta receptor blockade, and the decrease in PRA.

Adrenergic beta-Antagonists↗
PubMed1976

Abnormalities in the adrenergic control and the rate of lipolysis in isolated human subcutaneous adipose tissue in diabetes mellitus.

Subcutaneous adipose tissue was obtained from 9 patients with untreated diabetes mellitus and from 13 obese nondiabetics. After incubation with isoprenaline or noradrenaline, glycerol release and tissue cyclic AMP (cAMP) were determined. Basal glycerol release was twice as rapid from the diabetic adipose tissue. With isoprenaline, the cAMP concentration and the glycerol production was significantly higher in the diabetic adipose tissue. Noradrenaline did not increase glycerol production or cAMP concentration in the diabetic adipose tissue. Subcutaneous adipose tissue was also removed from the diabetics after antidiabetic treatment. Basal lipolysis was significantly reduced and noradrenaline significantly increased both glycerol release and cAMP production. With isoprenaline, cAMP production and glycerol release were significantly less after antidiabetic treatment than in the untreated state. The data provide evidence for increased alpha- as well as beta-adrenergic receptor sensitivity in human subcutaneous adipose tissue of untreated diabetic patients.

Adipose Tissue↗
PubMed1976

Metabolism of mono- and diacylglycerols in subcutaneous adipose tissue of obese and normal-weight subjects.

Tissue monoacylglycerols (MG), diacylglycerols (DG), free fatty acids (FFA), and cyclic AMP (cAMP) and release of FFA and glycerol have been studied in vitro in subcutaneous adipose tissue of 6 obese and 7 normal-weight subjects. The tissue was incubated without or with 6 X 10(-5) mol/l of isoprenaline (ISNA). The DG level and the fat cell volume were strongly interrelated (r=+0.95, p less than 0.001). The concentration of DG was increased (p less than 0.05) in obesity. The changes in DG and MG were significantly interrelated (r=+0.65, p less than 0.05) during basal incubation. ISNA increased the DG concentration in a way that was correlated (r=+0.81, p less than 0.001) with the ISNA-induced glycerol release. This indicates that 1) the basal metabolic activities of MG and DG lipase are similar and 2) DG lipase is an important rate limiting factor in lipolysis. Without ISNA, tissue FFA and the release of FFA and glycerol were significantly increased in the obese patients. As a mean, MG and DG did not accumulate in the basal state in the two patient groups. The findings indicate that basal lipolysis was increased in obesity. This was probably due to increased basal metabolic activity of triacylglycerol lipase, since the basal cAMP levels were similar in the two patient groups. In the presence of ISNA, the production of FFA and the glycerol release were similar in both patient groups, as was the increase in tissue DG. Also the ISNA-induced maximal level of cAMP was similar in the two groups. With ISNA, a small increment of MG was observed in adipose tissue of the normal-weight subjects. Taking all metabolites into account, the rate of lipolysis as well as the activation of triacylglycerol lipase via cAMP in the presence of ISNA appeared to be unaltered in obesity. Separate experiments with 1-14C-glycerol provided further evidence for the existence of a MG pathway for the esterification of FFA.

Adipose Tissue↗
PubMed1976

Survival of isolated human islets of Langerhans maintained in tissue culture.

Transplantation of human pancreatic islets to diabetic patients may require that donor islets be kept viable in vitro for extended time periods before transfer to the recipient. We have maintained isolated pancreatic islets obtained from the human cadaveric pancreas in tissue culture for 1-3 wk, after which we studied the structure and function of the islets. Electron micrographs of the cultured islets showed a satisfactory preservation of both beta-cells and alpha 2-cells. After culture for 1 wk, the islet oxygen uptake proceeded at a constant rate at a low glucose concentration (3.3 mM) and was significantly enhanced by raising the glucose concentration to 16.7 mM. Likewise, after culture for 1 wk, the islets responded with an increased insulin release when exposed to 16.7 mM glucose with or without added theophylline (10 mM). Islets cultured for 1-3 wk were able to incorporate [3H]leucine into proinsulin, as judged by gel filtration of acid-alcohol extracts. Glucagon release from the cultured islets was reduced significantly by 16.7 mM glucose alone, but stimulated by glucose (16.7 mM) plus theophylline (10 MM). It is concluded that viable pancreatic islets can be isolated from the pancreas of adult human donors and maintained in tissue culture for at least 1 wk without loss of the specific functions of the alpha 2- and beta-cells. It remains to be established whether such islets will survive and remain functionally competent after transplantation to human recipients.

Culture Techniques↗
PubMed1976

Changes in the adrenergic control and the rate of lipolysis of isolated human adipose tissue during fasting and after re-feeding.

The influence of changes in nutritional state on lipid mobilization has been investigated, using subcutaneous fat portions removed from 8 obese patients submitted to fasting for one week. The maximal rise in the tissue level of cyclic AMP (cAMP) and the rate of glycerol release were determined when adipose tissue was exposed to noradrenaline (6 X 10(-6) mol/1), isopropylnoradrenaline (6 X 10 (-6) mol/1) or none of the agents (basal medium). Fasting resulted in significant increases in the tissue level of cAMP and the rate of lipolysis in adipose tissue unexposed to lipolytic agents. Noradrenaline decreased the level of cAMP, in contrast to isopropylnoradrenaline, and significantly inhibited the rate of lipolysis during fasting. These noradrenaline effects were abolished by the simultaneous presence of phentolamine (13 mmol/1) in the incubation medium. Re-feeding with Meritene for one day resulted in a diminished rate of basal lipolysis, whereas the cAMP level was unaffected. The response of the cAMP accumulation to isopropylnoradrenaline was further augmented by re-feeding. Noradrenaline produced a significant rise in the level of cAMP and significantly stimulated the rate of glycerol production. It is concluded that the nutritional changes are of significance for the adrenergic regulation of lipolysis as indicated by the response of cAMP to the catecholamines. In pharmacological terms, fasting for one week resulted in increased alpha-as well as beta-adrenergic responsiveness. Increased basal lipolysis during fasting may be related to an increased level of cAMP or a direct activation of lipase.

Adipose Tissue↗
PubMed1976

Rejection of isolated pancreatic allografts in patients with with diabetes.

Four patients with diabetes mellitus of juvenile onset but without uremia have been treated with segmental transplantation of the body and tail of pancreas. The indications were hyperlabile diabetes or progressive loss of vision. The grafts were procured from cadaveric donors four to 16 minutes after circulary arrest and were subsequently stored in the cold for approximately four hours. In one patient, the pancreatic duct was ligated, while in the other three, drainage was attained by suturing the transected end of the pancreas into a jejunal Roux-en-Y loop. Three of the grafts failed within six weeks as a result of irreversible refection, and one graft failed because of the early onset of venous thrombosis. The first sign of graft rejection was an increase in the postprandial blood sugar level, an increase in the fasting blood sugar level occurring several days later. Neither hyperamylasemia nor fever was observed. Radioisotope scans and angiograms were of great value in establishing the diagnosis of graft rejection. All of the patients survived after graft removal.

Adult↗
PubMed1975

Cell size and the antilipolytic effect of insulin in human subcutaneous adipose tissue.

Lipolysis was studied in subcutaneous adipose tissue removed under local or general anaesthesia from subjects with marked difference in body weight and from obese subjects before and after intestinal shunt operations. The release of glycerol was measured in sections of adipose tissue incubated for two hours in bicarbonate buffer containing 4 per cent bovine albumin with no glucose added. The larger fat cells were more insulin sensitive than the smaller. A positive relationship was observed between the fat cell size and the antilipolytic effect of insulin (100 muU/ml). Insulin had no significant effect on the lipolytic effect of the catecholamines, when this is calculated as the increment in the glycerol release above the basal.

Adipose Tissue↗
PubMed1975

Methodological aspects of protein-binding assays for cyclic AMP in human adipose tissue.

The specificity of the protein-binding assay for cyclic AMP according to Gilman's method (11) was studied in human adipose tissue. A kit assay obtained from Boehringer-Mannheim was used for the study. Impurities in the solvents used for homogenization and extraction influenced the assay and led to serious overestimation of the actual amount of cAMP. This was corrected for by treating the standard and tissue samples in the same manner. Extracts from human adipose tissue contained material that increased the binding of cAMP to the binding protein and let to underestimation of intracellular cAMP by 60-70 per cent. This was overcome by using a protein kinase inhibitor in the assay. Furthermore, when human adipose tissue was incubated in an albumin-containing medium, intracellular cAMP was underestimated by 30 per cent, since albumin increased the binding of camp to the binding protein.

Adipose Tissue↗