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Biomedical subjects

P Björgell

Publications and source records attributed to P Björgell.

9 recordsLinked to original sources
PubMed1999

The effects of tolbutamide on lipoproteins, lipoprotein lipase and hormone-sensitive lipase.

Type 2 diabetic patients are at increased risk to develop atherosclerotic vascular disease. These patients are often treated with sulphonylurea derivatives, and it has been suggested that this treatment might contribute to the increased atherosclerotic process. The aim of the present study was therefore to investigate whether tolbutamide influences lipid metabolism in such a way that the atherosclerotic process may be promoted. Addition of tolbutamide (5-500 mg/l) to isolated rat fat adipocytes inhibited the lipoprotein lipase (LPL) activity in a dose-dependent manner to levels about 50% of those registered in the absence of tolbutamide. This effect was due to inhibition of the activation of the enzyme in the tissue and not to interference with the interaction of enzyme with its substrate. Addition of tolbutamide (500 mg/l) also inhibited noradrenaline (100 nM) and isoprenaline (40 nM)-induced lipolysis by 48.1 +/- 7.4% (mean +/- S.E.M.) and 47.3 +/- 5.5%, respectively. The decreased lipolysis in tolbutamide preincubated adipocytes was shown to be the result of an inhibition of the phosphorylation of hormone sensitive lipase (HSL). Three months of tolbutamide treatment (0.5 g t.i.d.) in diet treated type 2 diabetic patients did not influence the plasma concentrations of cholesterol, triglycerides, LDL cholesterol, HDL cholesterol as well as HDL triglycerides and HDL phospholipids, and there were no differences compared to placebo treated patients. There was a tendency towards a decrement in the elimination rate of exogenous triglycerides in the tolbutamide group (P = 0.0801). No differences between the groups and no treatment effects were seen on LPL and hepatic lipase activities. In conclusion, our in vitro data show that tolbutamide has dual effects on lipid transport, with impairment of the LPL system, which would tend to decrease plasma lipoproteins by reducing hepatic production of lipoproteins. In vivo, these two effects seem to balance each other and plasma lipoprotein levels remain unaffected.

Adipocytes↗
PubMed1999

Medical audit changes physicians' prescribing of antibiotics for respiratory tract infections.

OBJECTIVE: To reduce the prescribing of antibiotics in respiratory tract infections (RTI). DESIGN AND SUBJECTS: The Audit Odense model for registration and quality development was used for RTI. Twenty general practitioners registered their consultations for RTIs during 4 weeks in February-March (n = 1124) and November-December (n = 926) in 1995. Diagnosis, choice of antibiotics and diagnostic tools were registered. In between the two registrations an active intervention took place. Consultations for RTIs among 25 physicians (who had not participated in any intervention or follow-up discussion) served as a control. SETTING: General practice in southern Sweden. OUTCOME MEASURES: Prescribing of antibiotics before and after an intervention. RESULTS: The proportion of patients not receiving an antibiotic increased from the first to the second registration in both groups, in the intervention group from 45 to 55% (p < 0.001) and in the control group from 36 to 40% (p = 0.0298). The reduction was most evident in patients diagnosed with tonsillitis and bronchitis. This was in concordance with an increase in the use of desktop diagnostics (Strep A and CRP). CONCLUSION: These results indicate that it is possible to achieve a change in the utilisation of antibiotics in the treatment of RTIs and that the Audit Project Odense (APO) model could be a valuable tool.

Anti-Bacterial Agents↗
PubMed1990

Effects of a tocolytic oxytocin analogue on lipid and carbohydrate metabolism.

The effect of a newly developed tocolytic oxytocin analogue, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin on lipid and carbohydrate metabolism was investigated. Oxytocin and vasopressin both stimulated lipogenesis in isolated rat adipocytes, an effect which was dose-dependently inhibited by the oxytocin analogue. In vivo, intravenous injection of 10 nmol/kg body weight of the analogue to 11 healthy subjects caused an initial, but insignificant peak after 4 min in both plasma glucose and glycerol, which thereafter remained at basal level. It is concluded that although an antagonistic effect of the analogue on vasopressin- and oxytocin-stimulated lipogenesis could be demonstrated in vitro, the effect on lipid and carbohydrate metabolism in vivo in humans is insignificant.

Adipose Tissue↗
PubMed1984

Hormonal regulation of hormone-sensitive lipase in intact adipocytes: identification of phosphorylated sites and effects on the phosphorylation by lipolytic hormones and insulin.

In isolated adipocytes, fast-acting lipolytic hormones and insulin have been shown previously to control lipolysis by regulating the activity of hormone-sensitive lipase, the rate-limiting enzyme, through an increase or decrease, respectively, of the extent of phosphorylation of the enzyme. Here, we demonstrate that exposure to lipolytic hormones (corticotropin, noradrenaline) led to phosphorylation at two sites on the Mr 84,000 lipase subunit. One, designated "basal site," was phosphorylated also in the absence of any hormonal stimulation, its phosphorylation apparently not being influenced by hormones. The second, designated "regulatory site," was identical to that phosphorylated by cyclic AMP-dependent protein kinase on the isolated lipase. The regulatory site was not appreciably phosphorylated in the absence of hormones, but exposure of the cells to noradrenaline increased its phosphorylation extent to that of the basal site. Insulin or the beta-adrenergic antagonist propranolol decreased the extent of phosphorylation of the regulatory site to the low level before stimulation, apparently without effect on the basal site. Phosphoserine was the only phosphorylated amino acid residue at both sites. Limited proteolytic digestion indicated that the two sites were separated by less than about 170 amino acid residues. Thus, control of adipose tissue lipolysis by fast-acting lipolytic hormones and by insulin is exerted through the regulation of the phosphorylation state of a single phosphoserine residue in the hormone-sensitive lipase.

Adipose Tissue↗
PubMed1984

The antilipolytic, insulin-like effect of growth hormone is caused by a net decrease of hormone-sensitive lipase phosphorylation.

The mechanism of the antilipolytic effect of GH and the cause of refractoriness to its own action was studied in isolated rat adipocytes. Human GH rapidly inhibited catecholamine-stimulated lipolysis rate, with a time course similar to that of insulin, but only in cells which had been preincubated in the absence of GH for 2-3 h. Half-maximal inhibition was obtained with a GH concentration of 100 ng/ml. Parallel determinations of the lipolysis rate (with a pH-stat titration technique) and the extent of phosphorylation of hormone-sensitive lipase, the rate-controlling enzyme in adipose tissue lipolysis, were made. The extent of lipase phosphorylation, 1.7-fold enhanced by previous noradrenaline stimulation, was rapidly reversed by addition of GH, and the decrease was followed by a parallel decrease in the lipolysis rate. The time course and magnitude of these effects was similar to those obtained with exposure of the cells to insulin, indicating that the antilipolytic effect of both hormones was exerted through the same mechanism: a net dephosphorylation of the hormone-sensitive lipase. To study the refractoriness of the fat cells to the action of GH (which was not found with insulin) adipocytes were prepared from hypophysectomized rats 24 h after surgery. With such cells no preincubation was required to obtain the effects of GH on the lipolysis rate and extent of hormone-sensitive lipase phosphorylation. The effects of GH on both of the parameters studied were similar to those obtained in nonhypophysectomized rats. These results suggest that the refractoriness of the fat cells to GH may be explained by a functional inhibition at a site(s) in the series of metabolic events initiated by GH action, which precedes the activation of the hormone-sensitive lipase.

Adipose Tissue↗
PubMed1982

Characteristics of the lipolytic beta-adrenergic receptors in hamster adipocytes.

Hamster adipocyte beta-adrenergic receptors were characterized by the effect on the lipolysis rate of several selective beta-adrenergic agonists and antagonists. Prenalterol and procaterol, selective beta 1- and beta 2-agonists, respectively, both stimulated the lipolysis rate half-maximally at 1-2 microM, a concentration approximately 100-fold higher than that needed for half-maximal stimulation by isoprenaline. The maximal procaterol effect was similar to that of isoprenaline, while the effect of prenalterol was 40% lower. Submaximally isoprenaline-stimulated lipolysis was half-maximally inhibited by propranolol at 0.2 microM and by atenolol and H 35/25, selective beta 1- and beta 2-antagonists, at 23 and 6 microM concentration, respectively. Highly specific beta 1 and beta 2 stimulation was induced by incubation with prenalterol or procaterol, with simultaneous maximal selective beta 2 or beta 1 inhibition, respectively. The maximal beta 2 stimulation was approximately twice the corresponding beta 1 effect under these conditions, the sum of both effects closely approaching that of maximal nonselective beta-adrenergic stimulation with isoprenaline. Similar results were obtained with the selective beta 2-antagonist, ICI 118,551, or the beta 1-antagonists, pamatolol and practolol. The findings are most easily explained by the existence of a heterogeneous beta 1- and beta 2-adrenergic receptor population on hamster adipocytes.

Adipose Tissue↗
PubMed1981

Effects of insulin on lipolysis and lipogenesis in hamster white adipocytes with high sensitivity to hormones.

A modified procedure for preparation of hamster adipocytes by collagenase digestion under carefully controlled conditions has been developed. The adipocytes were 4- to 8-fold more sensitive to catecholamine stimulation of lipolysis than cells prepared by a commonly used method (Hittelman, K.J., Wu, C.F. and Butcher, R.W. (1973) Biochim. Biophys. Acta 304, 188-196) and also more sensitive to the anti-lipolytic action of insulin. The effects of insulin on lipogenesis, measured as [3H]glucose conversion to cell lipids, and on catecholamine-stimulated lipolysis were compared under identical conditions with the same cell batch. Isoprenaline-stimulated lipolysis was found to be half-maximally inhibited by an insulin concentration 8-fold lower than that stimulating lipogenesis to a corresponding extent (half-maximal effects at insulin concentrations of 40 vs. 300 pM). A similar difference was found when cells had been stimulated with adrenaline instead of isoprenaline.

Adipose Tissue↗