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Biomedical subjects

J Ostman

Publications and source records attributed to J Ostman.

At least 127 records · Page 7Linked to original sources
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

Influence of aging on insulin receptor binding and metabolic effects of insulin on human adipose tissue.

The influence of aging on the peripheral action of insulin was studied using subcutaneous adipose tissue from eight young (range 22-30 yr) and seven middle-aged (40-59 yr), healthy, normal-weight subjects. Insulin binding per cell was 50% lower in the older than in the younger group (P less than 0.01), essentially owing to a decrease in the insulin receptor number. Concomitantly, insulin sensitivity, as reflected in the degree of antilipolysis and stimulation of glucose oxidation, was 10-20 times smaller in the older subjects (P less than 0.01). Basal lipolysis and the maximum antilipolytic effect of insulin were similar in the two groups. The basal rate of glucose oxidation in the older subjects was less than one-half that for the younger group (P less than 0.025), and the maximum level of insulin-induced glucose oxidation was lower by about 75% (P less than 0.012). Age was significantly and negatively correlated with insulin receptor number (r = -0.81), basal production of 14CO2 (r = -0.73) and maximum level of insulin-induced glucose oxidation (r =- -0.68). The decreases in the receptor number and insulin sensitivity were larger in early adulthood than in the elderly, while the decrease in insulin responsiveness was more uniform. It is concluded that aging is accompanied by impairment of the action of insulin on target cells, owing to alterations at both the receptor and the postreceptor levels. These mechanisms, and especially the postreceptor defect, may be essential factors in the development of relative glucose intolerance in the aged.

Adipose Tissue↗
PubMed1983

Differences at the receptor and postreceptor levels between human omental and subcutaneous adipose tissue in the action of insulin on lipolysis.

The possible existence of regional differences in the antilipolytic action of insulin in human adipose tissue was investigated in vitro. Insulin-induced inhibition of glycerol release and insulin binding, measured in terms of receptor number, receptor affinity, and dissociation rates, were determined in omental and subcutaneous adipose tissue segments and isolated fat cells of 16 nonobese subjects who were undergoing elective abdominal surgery but were otherwise healthy. The sensitivity of the antilipolytic effect of insulin was higher in subcutaneous than in omental adipose tissue; the half-maximal effect was obtained with 1 and 3 microU/ml of insulin, respectively (P less than 0.01). Responsiveness of the antilipolytic effect of insulin was threefold higher in the subcutaneous than in the omental region (P less than 0.005). Insulin receptor affinity was significantly higher in subcutaneous than in omental fat cells, but there was no difference in receptor number (about 300,000 sites/cell). 125I-insulin dissociated more rapidly from omental than from subcutaneous adipocytes in both the absence and the presence of excess native insulin. The data suggest that significant regional differences exist in the antilipolytic action of insulin in man; omental fat being less responsive than subcutaneous fat. The difference involves the insulin receptor affinity, which is caused at least partly by variations in the insulin dissociation rate but is also due to differences in insulin action at the postreceptor level.

Adipose Tissue↗
PubMed1983

beta-adrenergic blockade and diabetes mellitus. A review.

The use of beta-blockers in diabetes mellitus has largely been restricted because of the reported adverse effects. Clinical investigations aimed at elucidating the possible reactions associated with the use of beta-blockers have disclosed no evidence of masking or signs or insulin-induced hypoglycaemia or potentiation of the insulin effect. Prolonged hypoglycaemia may develop, however, as a result of physical effort. There is no proof that during insulin-induced hypoglycaemia the concentrations of counter-regulatory hormones are depressed, but that of glycerol, a gluconeogenic precursor, is slightly diminished. Intensification of the hypertensive reaction during hypoglycaemia is less likely to occur during treatment with beta-selective blockers. In insulin-dependent diabetics receiving beta 1-blockers there is no evidence of any change - either deterioration or improvement - in metabolic control. In one small controlled trial there was no sign of impairment of the peripheral arterial circulation over a short period of administration of a non-selective beta-blocker. In general, for patients suffering from insulin-dependent diabetes, cardioselective agents are preferable. Since cardioselectivity is a dose-dependent property, reasonable caution should also be observed when using this type of drug in diabetes.

Adrenergic beta-Antagonists↗
PubMed1983

Can adequate control of diabetes prevent the development of vascular complications? A mini review.

Altogether, histologic findings in animals and in man with diabetes mellitus, together with clinical findings in man with this disease and with biochemical abnormalities, suggest that the main cause of microangiopathy in persons with diabetes mellitus lies in metabolic disorders. The possibility that genetic and environmental factors are influential cannot, however, be ruled out. In a small although steadily increasing number of diabetics early microangiopathic and neuropathic abnormalities have proved to be reversible. This improvement includes functional abnormalities of the retina, glomeruli and nerves. Early morphologic changes of the retina also, seem to be preventable. On the other hand, more severe morphologic changes such as proliferative retinopathy, and severe diabetic neuropathy have proved resistant to intensified insulin treatment. It remains to establish whether continuous optimal control by insulin treatment generally can prevent early although clinical microangiopathy. The development of instruments and other aids for improved metabolic control, such as transplantation of insulin-producing tissue, would seem to be a logical step in this direction.

Animals↗
PubMed1982

Successful outcome of segmental human pancreatic transplantation with enteric exocrine diversion after modifications in technique.

Segmental pancreatic transplantation is now the most widely favoured form of pancreatic transplantation, but the major difficulty with this procedure is the handling of the exocrine secretion. The use of a pancreaticoenteric anastomosis for exocrine diversion has been re-evaluated and several ancillary measures to reduce the risk of fistula and bacterial contamination have been applied. In three consecutive patients there have been no complications related to the exocrine pancreas. The pancreatic and renal grafts of these patients are functioning well 7, 3, and 2 months, respectively, after transplantation.

Adult↗
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

Effect of metoprolol and alprenolol on the metabolic, hormonal, and haemodynamic response to insulin-induced hypoglycaemia in hypertensive, insulin-dependent diabetics.

Insulin hypoglycaemia was induced three times in 6 insulin-dependent, hypertensive diabetics: before instituting antihypertensive long-term treatment and after obtaining a satisfactory blood pressure with either alprenolol or metoprolol given in a randomized order. The blood glucose concentration (1.6-1.9 mmol/l) at which the hypoglycaemia necessitated intravenous administration of glucose was almost identical on all three occasions. During hypoglycaemia the systolic and diastolic blood pressures increased significantly by a mean maximal rise of 27/14 mmHg on alprenolol treatment, but remained unchanged on metoprolol. The responses of adrenaline, noradrenaline, cortisol, and growth hormone did not differ significantly on the three occasions. None of the beta-adrenergic drugs counteracted the early hormone defence mechanisms in hypoglycaemia and the signs of hypoglycaemia were not masked. The haemodynamic response was altered only by the non-selective (alprenolol) and not by the selective beta-adrenergic blocking agent (metoprolol).

Adult↗
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

Postreceptor defects causing insulin resistance in normoinsulinemic non-insulin-dependent diabetes mellitus.

The mechanisms of the diminished hypoglycemic response to insulin in non-insulin-dependent diabetes mellitus (NIDDM) with normal levels of circulating plasma insulin were investigated. Specific binding of mono-125I (Tyr A14)-insulin to isolated adipocytes and effects of insulin (5--10,000 microunits/ml) on glucose oxidation and lipolysis were determined simultaneously in subcutaneous adipose tissue of seven healthy subjects of normal weight and seven untreated NIDDM patients with normal plasma insulin levels. The two groups were matched for age, sex, and body weight. Insulin binding, measured in terms of receptor number and affinity, was normal in NIDDM, the total number of receptors averaging 350,000 per cell. Neither sensitivity nor the maximum antilipolytic effect of insulin was altered in NIDDM patients as compared with control subjects; the insulin concentration producing half the maximum effect (ED50) was 10 microunits/ml. As regards the effect of insulin on glucose oxidation, for the control subjects ED50 was 30 microunits/ml, whereas in NIDDM patients, insulin exerted no stimulatory effect. The results obtained suggest that the effect of insulin on glucose utilization in normoinsulinemic NIDDM may be diminished in spite of normal insulin binding to receptors. The resistance may be due solely to postreceptor defects, and does not involve antilipolysis.

Adipose Tissue↗
PubMed1982

Increased peripheral insulin sensitivity and muscle mitochondrial enzymes but unchanged blood glucose control in type I diabetics after physical training.

Nine male, insulin-dependent diabetic patients participated in a 16-wk training program consisting of 1 h of jogging, running, ball games, and gymnastics, performed 2-3 times/wk. The training resulted in an 8% increase of maximal oxygen uptake (P less than 0.01). Insulin sensitivity as determined by the insulin clamp technique increased 20% (P less than 0.05). Glycosylated hemoglobin showed no change (10.4 +/- 0.7% versus 11.3 +/- 0.5%), 24-h urinary glucose excretion was not reduced, and home-monitored urine tests were unchanged. The frequency of hypoglycemic attacks did not change during the training period and body weight remained constant. There was a 14% fall in plasma cholesterol (P less than 0.01) and a rise in the proportion of HDL-cholesterol from 24 +/- 2% to 30 +/- 3% (P less than 0.01). Thigh muscle oxidative capacity increased, as indicated by a 24% increase in succinate dehydrogenase activity (P less than 0.05). The number of capillaries/muscle fiber increased 15% (P less than 0.01). However, as the mean muscle fiber cross-sectional area increased to a similar extent (11%, P less than 0.05), capillary density (cap x mm-2) was unchanged. In conclusion, this study demonstrates that physical training in insulin-dependent diabetics results in increased peripheral insulin sensitivity, a rise in muscle mitochondrial enzyme activities, decreased total plasma cholesterol levels, and unchanged blood glucose control. The findings suggest that in the absence of efforts to alter dietary regulation and insulin administration, physical training consisting of 2-3 weekly bouts of moderate exercise may not of itself improve blood glucose control in type I diabetes.

Adult↗
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↗