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Biomedical subjects

J Ostman

Publications and source records attributed to J Ostman.

At least 145 records · Page 8Linked to original sources
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

The antidiabetic effect and pharmacokinetic properties of glipizide. Comparison of a single dose with divided dose regime.

In 13 patients with maturity-onset diabetes mellitus which did not respond to diet therapy alone, serum concentration of glipizide, blood glucose (B-G) concentration, serum immunoreactive insulin (S-IRI) and plasma glycerol (P-G) were monitored hourly over 12 hours after placebo, an initial dose of glipizide (5 mg p.o.) and long-term treatment with glipizide (range 7.5--20 mg, mean 10.4), which produced fasting B-G of less than 8 mmol/l. During the long-term treatment, glipizide was given in a random, cross-over pattern, either as a single dose in the morning or as a three-part divided dose regime, in the same total daily amount. The duration of the immediate effects of glipizide on B-G, S-IRI and S-IRI/B-G was 9, 4.5 and 6.5 hours, respectively. The mean apparent half-life of glipizide was 4.1 hours, the mean distribution volume 0.13 l/kg and the mean plasma clearance 0.023 l/kg x h. The area under the concentration curve from 7.30 a.m. to 7.30 p.m. was 15% higher after the single dose regime. The serum levels of glipizide at 10 hours were only 30% lower than after the three-part divided dose regime. There were no significant differences between the single and divided dose regimes as regards B-G, S-IRI and S-IRI/B-G, although the mean B-G for the 12-hour period was somewhat lower after the former than after the latter (7.0 against 8.7 mmol/l).

Aged↗
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

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

Glucose tolerance following oral salbutamol treatment in late pregnancy.

Previous studies in pregnancy have shown that intravenous infusion of beta 2-sympathomimetic drugs, such as salbutamol, is followed by pronounced carbohydrate and lipid metabolic effects. Similar effects, though less pronounced, have also been demonstrated after oral salbutamol administration. Glucose elimination and insulin response after an intravenous glucose tolerance test (IVGTT) were analyzed in 12 women treated with oral salbutamol in the last trimester of pregnancy. IVGTT was performed without salbutamol and after at least 10 and up to 45 days of salbutamol treatment. No significant difference in either glucose elimination or insulin response to the glucose load were observed as a consequence of the salbutamol medication. This is in agreement with previous studies of other beta 2-sympathomimetic drugs and indicates that the use of salbutamol in late pregnancy does not give rise to serious disturbances of carbohydrate metabolism in healthy women.

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↗
PubMed1981

Neural crest tumour syndromes.

Cells eminating from the embryological neural crest can create different neoplasias, some of them endocrinological active and sometimes multiple (MEN or MEA). The relationship between these conditions and multiple neurofibromas is pointed out. Three cases of MEA which have been operated on at Huddinge Hospital are presented.

Adult↗
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

Monoamine metabolites in cerebrospinal fluid during treatment of hypertension with prazosin.

Six hypertensive patients were treated with prazosin up to a final dose of 3-4.5 mg/day. There was a significant reduction of blood pressure. The cerebrospinal fluid (CSF) concentrations of the major metabolites of noradrenaline, dopamine and serotonin were unchanged. This indicates that the antihypertensive effect is not mediated via central monoaminergic neurons as suggested by animal studies.

Biogenic Amines↗
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↗