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B Richelsen

Publications and source records attributed to B Richelsen.

At least 91 records · Page 5Linked to original sources
PubMed1991

[Health risks of obesity. Significance of the regional distribution of adipose tissue].

This review concentrates on recent prospective studies concerning evaluation of the health risk of obesity with special reference to the impact of the distribution of the adipose tissue. Analysis of the data indicates that adipose tissue localized to the abdominal region (especially intraabdominal fat) is associated with an enhanced risk profile including elevated levels of triglycerides and insulin, low levels of high density lipoprotein-cholesterol and elevated blood pressure. Abdominal obesity, determined by the waist/hip ratio, was associated with cardiovascular disease, premature death and non-insulin demanding diabetes mellitus. On the other hand, the total fat mass (measured as body mass index) was positively associated only with non-insulin demanding diabetes mellitus. The androgen/estrogen activity seems to be an important factor for determining the topographical localization of the adipose tissue. The great amount of free fatty acids which may be released from the abdominal fat tissue seemed to be of great pathogenetic importance for the metabolic consequences of abdominal obesity. In conclusion, obesity and the abdominal localization of adipose tissue seem to be two separate entities with different pathogenesis and clinical consequences. The abdominal obesity is the type which is predominantly associated with enhanced health risks. These associations may result in an altered strategy of treatment of the obese population.

Abdomen↗
PubMed1991

Phosphoinositide metabolism in adipocytes from hypothyroid rats.

The effect of hypothyroidism on insulin- and epinephrine-stimulated phosphoinositide metabolism was investigated in rat adipocytes. Insulin-mediated phosphoinositide synthesis was enhanced by hypothyroidism (14.5 +/- 1.5% above basal level, control vs. 22.5 +/- 2.0% above basel level, hypothyroid, P less than 0.05). However, insulin did not stimulate hydrolysis of phosphoinositides to inositol phosphates, neither in control nor in hypothyroid rats. The alpha 1-adrenoceptor agonist (e.g. epinephrine) significantly stimulated the incorporation of myo-[3H]inositol into phosphoinositides (P less than 0.01) and hydrolysis of phosphoinositides (P less than 0.01), but this stimulatory action was unaffected by the hypothyroid state. The results suggest that hypothyroidism has differentiated effects on the hormone-regulated phosphoinositide metabolism and that the presumptive G-protein coupled to the alpha 1-adrenoceptor seems to be unaffected by hypothyroidism.

Adipose Tissue↗
PubMed1991

Regional differences in triglyceride breakdown in human adipose tissue: effects of catecholamines, insulin, and prostaglandin E2.

Regional variation of adipose tissue triglyceride breakdown (lipolysis) has been suggested to play a role for the health consequences of some forms of obesity. Thus, in the present study we investigated the regulation of lipolysis in isolated adipocytes obtained from different fat depots in females. Intra-abdominal adipose tissue (omental) and subcutaneous abdominal adipose tissue were obtained from the same individuals undergoing abdominal surgery (n = 9); in addition, adipocytes from the subcutaneous gluteal region (n = 12) and from mammary adipose tissue (n = 5) were investigated. The lipolytic/antilipolytic properties of epinephrine (EPI), insulin, clonidine, and prostaglandin E2 (PGE2) were investigated. The most prominent observation was that EPI had none or only minor lipolytic effect in adipocytes from the subcutaneous regions, but significantly enhanced lipolysis by approximately 500% in omental adipocytes (P less than .001). In the presence of the alpha 2-adrenergic antagonist, yohimbine, EPI had similar stimulatory effects (fourfold to fivefold) in all fat depots. The antilipolytic compounds, insulin and clonidine, had greatly reduced antilipolytic properties in omental adipocytes as compared with subcutaneous adipocytes (P less than .01 and P less than .05, respectively). On the other hand, PGE2 had similar antilipolytic properties in adipocytes from the various depots. In conclusion, we found great regional variation in the regulation of lipolysis. Particularly, EPI was much more lipolytic in omental adipocytes than in subcutaneous adipocytes, mainly due to an enhanced functional alpha 2-receptor activity in subcutaneous adipocytes. These in vitro data suggest that free fatty acids (FFA) are more readily mobilized from omental adipose tissue than from subcutaneous adipose tissue.

Adenosine↗
PubMed1990

Effect of near normoglycemia for 5 years on progression of early diabetic retinopathy and renal involvement.

The effect of strict metabolic control for 5 years on renal function and retinal morphology was estimated in 24 insulin-dependent diabetic individuals (age 29 +/- 8 years, diabetes duration 10 +/- 6 years) with albustix negative urine and minimal or no background retinopathy before the study. They were randomized to conventional insulin treatment (CIT) or continuous subcutaneous insulin infusion (CSII) with a portable pump. During CSII treatment the metabolic status was significantly improved. HbA1c fell from 8.9 +/- 2.0 to 7.4 +/- 1.3% (p less than 0.01) whereas HbA1c was unchanged during CIT treatment. The mean value of urinary albumin excretion (UAE) was not statistically significantly changed (from 12 +/- 10 mg/24 h to 13 +/- 5 mg/24 h in CSII patients and from 14 +/- 12 to 11 +/- 6 mg/24 h in CIT patients (p greater than 0.1). On the other hand, the elevated GFR values were significantly reduced in both CSII and CIT patients, 129 +/- 17 to 120 +/- 9 and 129 +/- 18 to 119 +/- 12 ml/min.1,73m2, respectively (p less than 0.05). Both the number of microaneurysms, haemorrhages and exudates tended to increase mor in CIT patients than in CSII patients during the 5 year study period, but the differences did not reach statistically significance (p greater than 0.1). Pump treatment did not induce proliferations or "cotton wool" exudates. We conclude that no statistically significantly differences between GFR values, UAE rates, and progression of background retinopathy was observed between normoalbuminuric IDDM patients treated for 5 years with CIT and CSII, respectively. However, due to the size of the material a type II error must be taken into consideration.

Adult↗
PubMed1990

Phosphoinositide metabolism in adipocytes from fed and fasted rats.

Phosphoinositide turnover was investigated in adipocytes from fed and 48 hour fasted rats. Insulin stimulated phosphoinositide synthesis both in adipocytes from fed and fasted rats. Fasting enhanced this effect of insulin 2-fold. Hydrolysis of phosphoinositides to inositol phosphates was not activated by insulin, neither transient after 2 minutes nor after 60 minutes stimulation. Under similar conditions, alpha 1-adrenergic receptor stimulation induced a pronounced inositol phosphate production. Thus, it is suggested that phosphoinositide hydrolysis is not involved in insulin action. The alpha 1-adrenergic effect was similar in adipocytes from fed and fasting rats.

Adipose Tissue↗
PubMed1989

Characterization of antilipolytic action of polyamines in isolated rat adipocytes.

The interactions of polyamines with the lipolytic system were studied in isolated rat adipocytes. Spermine, spermidine and putrescine significantly inhibited adenosine deaminase-stimulated lipolysis. An antilipolytic effect of spermine was detectable at a concentration of 0.25 mM (P less than 0.05). At a concentration of 10 mM all three polyamines inhibited the stimulated lipolysis by 50-60% (P less than 0.001). In addition, spermine enhanced the antilipolytic sensitivity of insulin. Spermine (1 mM) decreased the half-maximal inhibitory concentration of insulin from 320 +/- 70 pM to 56 +/- 20 pM (P less than 0.01). The antilipolytic effects and the cyclic-AMP-lowering effects of the polyamines were almost completely prevented in the presence of different phosphodiesterase (PDE) inhibitors (3-isobutyl-1-methylxanthine and RO 20-1724) and, in addition, polyamines had no effect on lipolysis stimulated by dibutyryl cyclic AMP, indicating that polyamines may inhibit lipolysis by activating the PDE enzyme. This latter suggestion was confirmed by demonstrating that spermine (5 mM) significantly enhanced the low-Km PDE enzyme activity (P less than 0.01). Finally, the amounts of polyamines present in isolated adipocytes were measured, and the estimated cytoplasmic concentrations were 0.02 mM (putrescine), 0.86 mM (spermidine), and 1.0 mM (spermine). It is concluded that polyamines may possibly be involved in the physiological regulation of triacylglycerol mobilization in adipocytes.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Polyamines in rat adipocytes: their localization and their effects on the insulin receptor binding.

Effects of polyamines on the insulin binding in isolated rat adipocytes were studied. In addition, the concentration of polyamines in adipose tissue was determined, and their localization revealed by fluorescence cytochemistry and immunocytochemistry. Spermine (0.1-10 mM) dose-dependently enhanced the insulin receptor binding; at a concentration of 5-10 mM spermine the insulin binding was enhanced by 100% above control values. Spermidine had a weaker effect than spermine whereas putrescine had no effect on insulin binding. Competition curves with unlabelled insulin indicated that spermine increased the insulin binding capacity without significantly affecting the binding affinity. Fluorescence and immunocytochemistry on adipose tissue localized the polyamines spermidine and/or spermine almost exclusively to the thin layer of adipocyte cytoplasm surrounding the lipid droplet. In addition, chemical analysis for polyamines in the adipocyte medium and in the cells indicated that a differential release of polyamines may have occurred from the cells. The possibility that polyamines may act as intracellular or intercellular (autocrine) regulators, modulating insulin binding, is discussed.

Adipose Tissue↗
PubMed1989

The effects of metformin on adipocyte insulin action and metabolic control in obese subjects with type 2 diabetes.

To investigate the mechanisms of action of metformin, insulin receptor binding and the activity of several insulin-controlled metabolic pathways were measured in adipocytes taken from 10 obese Type 2 diabetic patients treated for 4 weeks with either metformin (0.5 g x 3 daily) or matching placebo using a double-blind crossover design. Metformin therapy was associated with a significant fall in serum fructosamine levels (3.1 +/- 0.4 vs 2.8 +/- 0.4 mmol l-1, p less than 0.02) as well as fasting (10.8 +/- 2.4 vs 9.4 +/- 2.1 mmol l-1) and daytime (11.5 +/- 2.4 vs 10.0 +/- 2.2 mmol l-1) plasma glucose concentrations (p less than 0.05). Fasting and postprandial plasma levels of C-peptide and insulin were unchanged. While fasting plasma lactate concentrations remained unaltered after metformin, a rise was noted in response to meals (from 1.4 +/- 0.1 to 1.8 +/- 0.2 mmol l-1, p less than 0.05). Adipocyte insulin receptor binding was unaffected by drug treatment. Moreover, no insulin-like effects or post-binding potentiation of insulin action could be found on adipocyte glucose transport, glucose oxidation, lipogenesis, glycolysis or antilipolysis. A complementary in vitro study using adipocytes from non-obese healthy volunteers failed to show any direct effect of metformin on adipocyte insulin binding or glucose transport and metabolism, at media drug concentrations corresponding to therapeutic plasma levels.

Adipose Tissue↗
PubMed1988

Evidence that phorbol ester-activated pathways are not directly involved in the action of insulin in rat adipocytes.

The effects of 12-phorbol 13-myristate acetate (PMA) on glucose transport, glucose metabolism and lipolysis in rat adipocytes were examined. Alone, PMA (100 ng/ml) stimulated 2-deoxyglucose transport, glucose oxidation and lipogenesis by an amount corresponding to about 30-50% of the maximal insulin effect. The effect of PMA on the insulin-stimulated processes was additive at all insulin concentrations. Adenosine deaminase-stimulated lipolysis was enhanced by about 50% by PMA (100 ng/ml). Thus, in contrast to insulin, PMA had a lipolytic effect. The antilipolytic effect of insulin was unaffected by the presence of PMA, both ED50 and maximal inhibition of insulin were unchanged. In conclusion, it is suggested that phorbol esters may activate pathways other than those activated by insulin in rat adipocytes.

Adipose Tissue↗
PubMed1988

Prostaglandin E2 action and binding in human adipocytes: effects of sex, age, and obesity.

The antilipolytic effect of prostaglandin E2 (PGE2) was studied in subcutaneous human adipocytes. The influence of sex, age, and obesity on the PGE2 effect was investigated. The antilipolytic effects of PGE2 were related to the PGE2 binding data obtained in the same adipocytes. The maximal antilipolytic action of PGE2 was slightly reduced in adipocytes in males compared with females (maximal inhibition 86% v 97%, P greater than .05). The PGE2 binding was similar in adipocytes in females and males. The antilipolytic effect of PGE2 and the PGE2 binding was similar when young females were compared with older females. However, the antilipolytic effect of PGE2 was significantly reduced in obese compared with nonobese subjects. If lipolysis was only stimulated by adenosine deaminase, the sensitivity of PGE2 was reduced in obesity (IC50, 1.45 nmol/L v 0.47 nmol/L, P less than .01), but the maximal antilipolytic effect of PGE2 in the two groups was similar, with an inhibitory effect of 95% to 98%. If lipolysis was stimulated by both adenosine deaminase and theophylline (2 mmol/L), it was especially the maximal antilipolytic effect of PGE2 that was impaired in adipocytes from obese subjects (lipolysis was maximally inhibited by 61% v 92%, P less than .01). When the PGE2 binding was expressed in relation to adipocyte surface area, the total binding capacity (Bmax) was reduced in adipocytes in obese subjects from 26.5 to 17.9 fmol/100 cm2 (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase↗
PubMed1988

Interaction of indomethacin with the antilipolytic effect of prostaglandin E2 in rat adipocytes.

The interaction of indomethacin with the antilipolytic effect of prostaglandin E2 (PGE2) was investigated in rat adipocytes in order to reveal a possible role of endogenous PGs in adipose tissue. Adipocytes isolated from rats treated in vivo for 5 days with indomethacin were compared with non-treated control rats. The sensitivity of the antilipolytic effect of exogenous PGE2 was significantly enhanced in adipocytes from indomethacin-treated rats (IC50 of PGE2: 0.45 +/- 0.05 nM vs. 1.2 +/- 0.1 nM, P less than 0.01). This enhanced antilipolytic effect of exogenous PGE2 could be related to the reduced endogenous PGE2 formation in adipocytes from the indomethacin-treated rats (PGE2 formation was reduced by more than 90%). In agreement with that observation the [p3H]PGE2 receptor binding was enhanced by 58% in adipocytes treated with indomethacin. Thus, indomethacin via inhibition of endogenous PG formation could modulate some properties of lipolysis in adipocytes. However, indomethacin treatment had no significant effects on basal or isoproterenol-stimulated lipolysis.

Adipose Tissue↗
PubMed1988

A mixed meal potentiates the insulin sensitivity of glucose transport and metabolism in adipocytes from patients with type 2 diabetes mellitus.

Post-glucose enhancement of insulin action may represent a physiological mechanism for the acute regulation of insulin sensitivity of target tissues. To clarify whether a similar mechanism is operative in the insulin-resistant diabetic state we have investigated the effects of a mixed meal on adipocyte insulin action in eight patients with Type 2 diabetes mellitus. Ninety minutes after ingestion of breakfast insulin binding to fat cells increased by 21% (p less than 0.05). In the fasting state 6 patients had a significant response of glucose transport and lipogenesis to insulin whereas two exhibited non-responsiveness. In the 6 responders insulin sensitivity, as estimated by the insulin concentration at which half-maximal effect was achieved, increased for glucose transport (before, 260 +/- 46 pmoll-1; after, 105 +/- 21 pmol l-1; p less than 0.05) and for lipogenesis (before, 36 +/- 9 pmol l-1; after, 9 +/- 2 pmol l-1; p less than 0.05). No significant changes occurred in basal or maximal glucose transport or lipogenesis. In the two primary non-responders intake of the meal was associated with average increase in maximal insulin responsiveness of 52% for glucose transport and 28% for lipogenesis. Intake of a mixed meal is associated with a slight increase of insulin binding to adipocytes from patients with Type 2 diabetes mellitus but a marked increase of adipocyte insulin sensitivity at the post-binding levels of glucose transport and metabolism.

Adipose Tissue↗
PubMed1988

Comparative studies of insulin binding to receptor from adipocytes, hepatocytes, monocytes and erythrocytes from the pig. Similarities with insulin receptor binding in man.

We have described the receptor binding of A14-labelled [125I]insulin to viable adipocytes, hepatocytes, monocytes and erythrocytes from the pig. For all cell types the binding was of high affinity, specific for insulin, the non-specific binding low and degradation of insulin in the medium was minimal. At 24 degrees C, steady state insulin binding was achieved in all four cell types. At 37 degrees C, steady state insulin binding could be measured to adipocytes and hepatocytes. Specific insulin binding levels and receptor affinity for blood and fat cells from the pig are comparable to that in human cells, whereas differences, especially according to affinity, exist between pig and rat cell insulin receptor binding. It is therefore concluded that the pig is a more suitable model for studies of insulin binding in man than rodents. Finally, no correlations between the individual binding levels to the different cell types were observed. Hence, measurement of insulin binding to the easier available blood cells cannot replace studies of insulin binding to target cells of insulin.

Adipose Tissue↗
PubMed1988

Characterization of the insulin resistance of glucose utilization in adipocytes from patients with hyper- and hypothyroidism.

UNLABELLED: Insulin action on glucose utilization was characterized in adipocytes from 10 thyrotoxic patients, 6 hypothyroid patients and 10 age- and sex-matched control subjects. In thyrotoxic patients insulin binding at low insulin concentrations was reduced (P less than 0.05) and accompanied by impaired insulin sensitivity of glucose transport (P less than 0.02), glucose oxidation (P less than 0.05) and lipogenesis (P less than 0.05). Glucose transport and glucose oxidation rates also exhibited depressed maximal insulin responsiveness (P less than 0.05). In hypothyroid patients insulin binding was reduced, too, (P less than 0.05) and associated with impaired sensitivity to insulin of glucose transport (P less than 0.05). Both glucose transport and lipogenesis rates showed decreased maximal insulin responsiveness (P less than 0.05). IN CONCLUSION: In man, both hyper- and hypothyroidism are characterized by insulin resistance of adipocyte glucose utilization localized to insulin binding as well as to insulin-stimulated glucose transport and metabolism.

Adipose Tissue↗
PubMed1987

Factors regulating the production of prostaglandin E2 and prostacyclin (prostaglandin I2) in rat and human adipocytes.

The regulation of PGE2 (prostaglandin E2) and PGI2 (prostaglandin I2; prostacyclin) formation was investigated in isolated adipocytes. The formation of both PGs was stimulated by various lipolytic agents such as isoproterenol, adrenaline and dibutyryl cyclic AMP. During maximal stimulation the production of PGE2 and PGI2 (measured as 6-oxo-PGF1 alpha) was 0.51 +/- 0.04 and 1.21 +/- 0.09 ng/2 h per 10(6) cells respectively. Thus PGI2 was produced in excess of PGE2 in rat adipocytes. The production of the PGs was inhibited by indomethacin and acetylsalicylic acid in a concentration-dependent manner. The half-maximal effective concentration of indomethacin was 328 +/- 38 nM and that of acetylsalicylic acid was 38.5 +/- 5.3 microM. The PGs were maximally inhibited by 70-75% after incubation for 2 h. In contrast with their effect on PG production, the two agents had a small potentiating effect on the stimulated lipolysis (P less than 0.05). The phospholipase inhibitors mepacrine and chloroquine inhibited both PG production and triacylglycerol lipolysis and were therefore unable to indicate whether the PG precursor, arachidonic acid, originates from phospholipids or triacylglycerols in adipocytes. Angiotensin II significantly (P less than 0.05) stimulated both PGE2 and PGI2 production in rat adipocytes without affecting triacylglycerol lipolysis. Finally, it was shown that PGE2 and PGI2 were also produced in human adipocytes, although in smaller quantities than in rat adipocytes. It is concluded that the production of PGs in isolated adipocytes is regulated by various hormones. Moreover, at least two separate mechanisms for PG production may exist in adipocytes: (1) a mechanism that is activated concomitantly with triacylglycerol lipolysis (and cyclic AMP) and (2) an angiotensin II-sensitive, but lipolysis (and cyclic AMP)-independent mechanism.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Alpha 2- and beta-adrenergic receptor binding and action in gluteal adipocytes from patients with hypothyroidism and hyperthyroidism.

The alpha 2- and beta-adrenergic receptor activities have been investigated in human adipocytes in relation to thyroid status. Adipocytes from 11 hypothyroid and 18 hyperthyroid were compared with 19 euthyroid (normal) subjects. The lipolytic and cAMP responses to isoproterenol and epinephrine were greatly enhanced in adipocytes from hyperthyroid subjects (P less than .01) and impaired in adipocytes from hypothyroid subjects (P less than .05). However, the antilipolytic effect of clonidine (alpha 2-agonist) and the effect of clonidine on cAMP were similar in all three groups. The alpha 2- and beta-receptor numbers were both slightly increased in hyperthyroidism, but the ratio between the alpha 2- and beta-receptors was unchanged in relation to normal subjects. On the other hand, the adrenergic binding to adipocyte membranes from hypothyroid subjects was reduced, and the beta-receptor binding was reduced even much more (50%) than the alpha 2-receptor binding (20%, P less than .01). Thus, the alpha 2- and beta-receptor ratio was almost doubled in hypothyroid adipocytes (P less than .01). The antagonist affinity against the adrenergic receptors (determined by propranolol and yohimbine, respectively) was unchanged in the three groups. Agonist binding determined in intact adipocytes revealed unaltered affinity of clonidine for the alpha 2-receptor in the three groups. In hyperthyroidism, though, there was enhanced affinity of isoproterenol in competition with the beta-receptor (P less than .05). It is concluded that the inhibitory alpha 2-receptor pathway functions normally in all groups, indicating that the alpha 2-receptors and the alpha 2-receptor-mediated pathway in human adipocytes are relatively unaffected by thyroid hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗