Biomedical subjects

B Richelsen

Publications and source records attributed to B Richelsen.

At least 109 records · Page 6Linked to original sources

PubMed1987

Prostaglandin-E2 receptors in the rat kidney: biochemical characterization and localization.

A radiohistochemical technique yielding data on the distribution and characteristics of PGE2-receptor binding in tissue sections is described. The binding of tritiated PGE2 (3H-PGE2) to slide-mounted tissue sections had all the characteristics associated with ligand-receptor interactions: it was saturable, of high affinity and displayed high specificity for PGE2 binding. From the binding curves a Hill coefficient of 1.1 was calculated which suggests the presence of a homogeneous receptor population. Pretreatment with indomethacin for four days resulted in a 66% increase in maximal binding capacity (Bmax) without any change in affinity. The distribution of receptor was mapped in rats with and without indomethacin pretreatment and compared to the distribution of Tamm-Horsfall glycoprotein, a specific marker for the thick ascending limb of Henle. In both groups the PGE2 receptor showed striking regional variation. In the untreated group the distribution of PGE2 receptors was similar to that of the thick ascending limb of Henle, with maximal density in the outer medullary zone. After indomethacin pretreatment, however, a striking increase in inner medullary binding was observed together with increased binding in the cortex. Thus, in accordance with the main action of PGE2 being regulation of renal water and sodium excretion, we found the highest receptor density in areas of the kidney dominated by the thick ascending limb of Henle and collecting tubules, and much less binding to glomeruli and cortical vessels. In order to investigate characteristics and distribution of PGE2 receptor binding, however, it was mandatory that endogenous prostanoid synthesis is blocked.

Animals↗

PubMed1987

Diabetic retinopathy after 3 years' treatment with continuous subcutaneous insulin infusion (CSII).

Twenty-four insulin-dependent juvenile diabetics with no or minimal background retinopathy were randomly allocated to conventional insulin therapy (CIT) or continuous sc insulin infusion (CSII) administrated by a portable pump. At the present 3 year follow-up, there was one drop-out in the CSII group. Although the metabolic control was significantly better in the CSII patients, both groups improved significantly in metabolic control during the observation period. After 3 years, the HbA lc level was 7.4% +/- 1.2 (+/- SD) in the CSII patients and 8.6% +/- 1.6 in the CIT patients (P less than 0.01). As compared to the status at the beginning of the study, a progression of diabetic retinopathy (criteria: development of more than 2 microaneurysms) was observed in 4 of 11 in the CSII group and in 5 of 12 in the CIT group (P greater than 0.05). None of the patients were seen to develop soft exudates or neovascularisations. This study confirms the impression gained from a previous one-year follow-up of similar progression of retinopathy in patients on CSII and CIT.

Adult↗

PubMed1987

Antilipolytic effect of prostaglandin E2 in perifused rat adipocytes.

Previously, the antilipolytic effect of prostaglandin E2 (PGE2) has been investigated in conventional adipocyte incubations. To define the effect of PGE2 on lipolysis more clearly, isolated epididymal adipocytes were studied with the perifusion system. PGE2 inhibited isoproterenol (100 nM)- and theophylline (1 mM)-stimulated lipolysis in a concentration-dependent manner in both the perifusion system and conventional incubations. However, the half-maximally inhibitory concentration (ED50) of PGE2 on isoproterenol-induced lipolysis was about 0.4 nM in the perifusion system, whereas the ED50 was 8 nM in the static adipocyte incubations. The ED50 values of PGE2 on theophylline-induced lipolysis were 0.8 nM (perifusion) and 5 nM (incubation), respectively. Thus, the sensitivity of stimulated lipolysis to PGE2 was about 10 times higher in the perifusion system than in conventional adipocyte incubations. In addition, the maximal antilipolytic effect of PGE2 was greater in the perifusion system. At a concentration of 100 nM PGE2 inhibited theophylline-induced lipolysis by 82 +/- 5% in adipocyte incubations, whereas lipolysis was inhibited by 100 +/- 3.5% in the perifusion system (P less than 0.05). When lipolysis was stimulated by isoproterenol the maximal antilipolytic effect of PGE2 was an inhibition of 90 +/- 2.5% in the perifusion system and 55 +/- 5% in adipocyte incubations (P less than 0.05). Moreover, the maximal antilipolytic effect was obtained at a PGE2 concentration of 20 nM in the perifusion system, but at a concentration of 100 nM in static incubations. The release of immunoreactive PGE2 from adipocytes was measured by RIA. In the perifusion system no PGE2 could be detected in the effluent under basal conditions; however, during exposure to 100 nM isoproterenol a small amount of PGE2 was detected (3-4.5 pg/10(6) cells X min). Exogenous PGE2 was almost totally (90%) recovered in the effluent. In adipocyte incubations basal PGE2 production was 103 +/- 22 pg/10(6) cells X 60 min, whereas both isoproterenol and theophylline increased these amounts of PGE2 2-fold (P less than 0.01). It is concluded that exogenous PGE2 has pronounced antilipolytic properties at very low concentrations (subnanomolar) in perifused adipocytes. The reduced sensitivity and maximal responsiveness of PGE2 in static incubations may be related to accumulation of FFA and endogenous PGs, which may partially obscure the interaction of exogenous PGE2 with the adenylate cyclase complex.

Adipose Tissue↗

PubMed1986

Increased alpha 2- but similar beta-adrenergic receptor activities in subcutaneous gluteal adipocytes from females compared with males.

alpha 2 and beta-adrenergic binding and action were studied in subcutaneous adipocytes from the gluteal region in females and males. The beta-selective antagonist [3H]dihydroalprenolol and the alpha 2-selective antagonist [3H]yohimbine were used to identify the beta- and the alpha 2-receptor, respectively. The biological effects mediated by these receptors were determined by measuring the glycerol release induced by isoproterenol (beta-receptor agonist) and by clonidine (alpha 2-receptor agonist). The study consisted of health volunteers (eighteen females and fifteen males). Compared to men the alpha 2-receptor binding was increased by 73% (P less than 0.01) in adipocytes from females. From Scatchard analysis it was determined that the increased binding was due to an increased receptor number (438 v. 262 fmol mg-1 protein, P less than 0.001) with unaltered Kd (1.18 v. 1.35 nmol l-1, P greater than 0.05). This increased alpha 2-receptor binding in female and adipocytes was associated with a significantly increased sensitivity (P less than 0.05) and maximal antilipolytic effect of clonidine (P less than 0.05). The beta-receptor binding was similar in adipocytes from females and males. However, isoproterenol was significantly more lipolytic in female adipocytes (P less than 0.01). Since the combination of theophylline and adenosine deaminase also was significantly more lipolytic in female adipocytes the enhanced effect of isoproterenol then seemed to be due to mechanisms not directly related to the hormone-beta-receptor binding. Finally, the mixed beta- and alpha 2-receptor agonist, adrenaline showed biphasic effects on lipolysis, with stimulatory effect at low concentrations (less than 500 nmol l-1) and pronounced inhibitory effect at higher concentrations (greater than 1 mumol l-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1986

Reduced binding and antilipolytic effect of prostaglandin E2 in adipocytes from patients with hyperthyroidism.

The present study was undertaken to evaluate the effect of thyroid hormones on prostaglandin E2 (PGE2) binding and action in human adipocytes. The study consisted of 12 patients with hyperthyroidism and 20 normal subjects. In adipocytes from hyperthyroid patients, there was a 32% decrease in [3H]PGE2-binding sites (P less than 0.01). This reduced binding was accompanied by a 46% reduction in the relative antilipolytic effect of PGE2 in adipocytes from patients with hyperthyroidism. These changes might, then, account for some of the enhanced lipolysis that occurs in hyperthyroid patients. Thyroid hormones significantly increased the lipolytic effect of isoproterenol (P less than 0.01). However, the lipolytic effect of theophylline plus adenosine deaminase and basal lipolysis also were increased in adipocytes from hyperthyroid subjects. The latter findings indicate that thyroid hormones induce a state of increased activation of lipolysis under both basal and stimulated conditions. It is concluded that thyroid hormones reduce the binding and action of PGE2 in human adipocytes, possibly via a cAMP dependent mechanism. These alterations will contribute to accelerated lipid metabolism in the hyperthyroid state.

Adipose Tissue↗

PubMed1986

Continuous subcutaneous insulin infusion fails to correct impaired basal glucose metabolism and impaired insulin sensitivity of adipocytes from patients with type 1 (insulin-dependent) diabetes.

Studies of the in vivo insulin action in conventionally treated Type 1 diabetic patients have shown insulin resistance, especially in poorly controlled patients. We reported previously on impaired basal and insulin-stimulated glucose utilization in adipocytes from Type 1 diabetic subjects. In this study we have examined whether a near-normalization of glycaemia and plasma levels of metabolites in Type 1 diabetic patients induced by continuous subcutaneous insulin infusion might reverse abnormalities of adipose tissue metabolism. 11 Type 1 diabetic subjects who had been treated conventionally with diet and insulin for 11 yr were studied before and after continuous subcutaneous insulin infusion for 6 months. In Type 1 diabetic patients before insulin pump treatment we found decreased adipocyte insulin binding (p less than 0.01), normal insulin binding to monocytes and erythrocytes, impaired insulin sensitivity of the adipocyte glucose transport (p = 0.02) and reduced basal and maximally insulin-stimulated rates of adipocyte glucose oxidation and lipogenesis (all p less than 0.05). After pump therapy for 6 months we found a further reduction of basal and maximal adipocyte glucose oxidation and lipogenesis (all p less than or equal to 0.05), whereas we found no significant changes of insulin receptor binding or insulin sensitivity of adipocyte glucose utilization. We conclude that continuous subcutaneous insulin infusion of Type 1 diabetic patients for 6 months aggravates the defects in basal (non-insulin-stimulated) and maximally insulin-stimulated glucose utilization of isolated adipocytes despite an optimization of glycaemic control and a near-normalization of plasma metabolites.

Adipose Tissue↗

PubMed1985

Alpha 2-adrenergic binding and action in human adipocytes. Comparison between binding to plasma membrane preparations and to intact adipocytes.

Binding of the alpha 2-adrenoceptor antagonist [3H]yohimbine was demonstrated on intact human adipocytes and on human adipocyte membranes. Specific binding was rapid, reversible, saturable and of high affinity in both preparations. [3H]Yohimbine binding was inhibited by various adrenergic agents in a manner which suggests that the labeled sites probably represent the alpha 2-receptor both in intact adipocytes and in the membrane fraction. In adipocyte membranes the maximal binding capacity (Bmax) was 463 +/- 38 fmol/mg protein and the binding was of high affinity with a Kd of 2.1 +/- 0.4 nM. In intact human adipocytes, Bmax was 903 +/- 139 fmol/10(6) cells (or 342 +/- 21 fmol/100 cm2) and the binding affinity was 6.6 +/- 0.8 nM. Adrenergic antagonists bound to a homogeneous class of receptors (linear Scatchard plots) both in isolated membranes and in intact adipocytes. However, agonist binding was heterogeneous in both preparations. The affinity of agonist binding was 5-10 times higher in membranes than in intact adipocytes. The physiological relevance of the binding data was evaluated by correlating the binding of yohimbine with the antilipolytic effect of clonidine. A positive and significant correlation was found between Bmax and maximal antilipolytic effect of clonidine (r = 0.70) in membranes. Furthermore, the binding affinity (Kd) was positively correlated to the sensitivity (IC50) of the clonidine-induced antilipolysis (r = 0.65). A positive and significant correlation was also found in intact adipocytes between Bmax and the maximal antilipolytic effect of clonidine (r = 0.79). However, there was no significant correlation between Kd in intact adipocytes and the IC50 of clonidine. It is concluded that both intact human adipocytes and membrane fractions are useful models to investigate the properties and regulation of alpha 2-adrenoceptors. However, it appears from our correlation studies that the binding data obtained with the membranes are the best related to the physiological effects mediated by alpha 2-receptors in human adipocytes.

Adipose Tissue↗

PubMed1985

Effects of prostaglandin E2, indomethacin and adenosine deaminase on basal and insulin-stimulated glucose metabolism in human adipocytes.

The effects of prostaglandin E2 were studied on glucose metabolism (3-O-methylglucose transport, CO2 production and lipogenesis) in human adipocytes. Initially, the effects of endogenously produced adenosine and prostaglandins were indirectly demonstrated by using adenosine deaminase and indomethacin in the incubations. From these studies it was found that adenosine deaminase (5 micrograms/ml) had a pronounced effect on adipocyte glucose metabolism in vitro. In the basal (nonhormonal-stimulated) state, glucose transport, CO2 production and lipogenesis were inhibited by about 30% (P less than 0.05). Furthermore, adenosine deaminase significantly inhibited the isoproterenol- and insulin-stimulated CO2 production and lipogenesis (P less than 0.01). Indomethacin (50 microM) had a consistently inhibitory effect on the insulin-stimulated CO2 production (P less than 0.05), whereas indomethacin had no significant effects on basal or isoproterenol-stimulated glucose metabolism. In contrast to the relatively minor effect of endogenous prostaglandins, the addition of exogenous prostaglandin E2 significantly stimulated the glucose transport, glucose oxidation and lipogenesis in human adipocytes, especially in the presence of adenosine deaminase. Half-maximal stimulation was obtained at prostaglandin E2 concentrations of 2.2, 0.8 and 0.8 nM, respectively. The effect of prostaglandin E2 was specific, since the structurally related prostaglandin, prostaglandin F2 alpha, had practically no effect on glucose metabolism. The maximal effect of prostaglandin E2 (1 microM) on glucose metabolism was 30-35% of the maximal insulin (1 nM) effect. When insulin and prostaglandin E2 were added together, the effect of prostaglandin E2 on glucose metabolism was additive at all insulin concentrations tested.

3-O-Methylglucose↗

PubMed1985

Postbinding defects of insulin action in human adipocytes from uremic patients.

It is now well established that longstanding human uremia is associated with impaired in vivo insulin action on glucose utilization of peripheral target tissues. In an attempt to define the cellular basis of the uremic insulin resistance we studied insulin action in adipocytes from eight patients with undialyzed chronic uremia and from eight matched healthy controls. (125I)-Insulin binding to fat cells from uremic patients was normal. In contrast (14C)-D-glucose transport exhibited decreased sensitivity to insulin. The concentrations of insulin that elicited half-maximal response was 422 +/- 95 pmoles/liter in uremic patients and 179 +/- 38 pmoles/liter in normal subjects (P less than 0.01). The noninsulin- and the maximal insulin-stimulated glucose transport of adipocytes from uremic patients with normal. (14C)-D-glucose conversion to total lipids was also measured in these cells in the absence and presence of various insulin concentrations. Similar to the findings in transport studies the lipogenesis of fat cells from uremic patients had depressed sensitivity to insulin (half-maximal stimulation at 38 +/- 8 pmoles/liter in uremic patients and at 11 +/- 3 pmoles/liter in normal subjects, P less than 0.01) with unchanged noninsulin and maximal insulin-stimulated lipogenesis. Taken together these results suggest that the insulin resistance of adipocytes from patients with chronic uremia may be accounted for primarily by postbinding defects localized to glucose transport and metabolism.

Adipose Tissue↗

PubMed1985

Prostaglandin E2 receptors on human peripheral blood monocytes.

The prostaglandin E2 (PGE2) receptor on human peripheral blood monocytes is characterized. The receptor binding at physiological temperature and pH was saturable, specific, and reversible. Scatchard analysis of binding data revealed a linear plot giving a Kd = 1.1 X 10(-9) mol/l and Bmax = 4.1 fmol/10(7) cells, equal to 240 binding sites per cell. PGE2 increased intracellular cyclic adenosine 5'-monophosphate by a maximal factor of 3. PGF2 alpha and arachidonic acid had no stimulatory effects on adenyl cyclase, in accordance with their low binding to the cells. The characterization of the PGE2 receptor on human monocytes creates a basis for the study of the clinical significance of changes in PGE2-receptor binding in disease states involving PGE2-monocyte interactions such as various immunological disorders and bone resorption.

Arachidonic Acid↗

PubMed1985

Defective non-insulin-mediated and insulin-mediated glucose transport and metabolism in adipocytes from obese and lean patients with untreated type 2 diabetes mellitus.

Insulin binding, glucose transport, and glucose metabolism were investigated in isolated adipocytes from 11 lean and 13 obese patients with non-insulin-dependent diabetes mellitus. Insulin binding at 15 degrees C was reduced by 35% (p less than 0.01) in both lean and obese diabetic patients, whereas insulin binding (or uptake) at 37 degrees C was similar in diabetic patients and healthy controls. In lean diabetic patients both non-insulin-mediated (basal) and maximally insulin-stimulated glucose transport and metabolism were significantly reduced (all p less than 0.01). The percentage responses to insulin were also markedly reduced (p less than 0.05, p less than 0.02). In obese diabetic patients basal glucose transport was reduced (p less than 0.01) but basal glucose metabolism was not. Insulin-stimulated glucose transport and metabolism were significantly reduced (p less than 0.01, p less than 0.05). The percentage responses were reduced compared to healthy controls (p less than 0.05, p less than 0.05) but higher than in lean diabetic patients (p less than 0.05). We conclude that adipocytes isolated from both lean and obese patients with non-insulin-dependent diabetes mellitus are characterized by severely depressed non-insulin-mediated and insulin-mediated glucose transport and depressed insulin-mediated glucose metabolism. The major defect seems to be a reduced maximal effect of insulin on glucose metabolism, suggesting post-binding and post-transport abnormalities.

Adipose Tissue↗

PubMed1985

Glucose transport and metabolism in adipocytes from newly diagnosed untreated insulin-dependent diabetics. Severely impaired basal and postinsulin binding activities.

Previous studies have shown cellular insulin resistance in conventionally treated insulin-dependent diabetics. To determine whether insulin resistance is also present in insulin-dependent diabetics before the commencement of insulin therapy, we studied nine newly diagnosed untreated insulin-dependent diabetics and nine control subjects. Insulin binding to adipocytes, monocytes, and erythrocytes was normal in the diabetic individuals. Basal (noninsulin stimulated) glucose transport rate was normal, whereas the maximal insulin responsiveness of glucose transport was severely impaired (P less than 0.02). Insulin sensitivity as judged by left or rightward shifts in the insulin dose-response curves was unchanged. Moreover, the basal lipogenesis rate measured at a glucose concentration of 0.5 mmol/liter was decreased in the diabetics (P less than 0.05), and the maximal insulin responsiveness of lipogenesis was also reduced (P less than 0.05). We conclude that fat cells from untreated insulin-deficient diabetics are insulin resistant. The major defects are (1) reduced maximal insulin responsiveness of glucose transport and conversion to lipids that are postbinding abnormalities, and (2) reduced basal glucose conversion to lipids.

Adipose Tissue↗

PubMed1985

Beta-adrenergic regulation of prostaglandin E2 receptors in human and rat adipocytes.

Incubation of intact human and rat adipocytes with isoproterenol (10(-6) M) inhibits the specific binding of [3H] prostaglandin E2 (PGE2) by about 25% in human adipocytes and 50% in rat adipocytes. Scatchard analysis of [3H]PGE2 binding demonstrated that the isoproterenol-induced decrease in receptor activity may be due to a decrease in the apparent number of PGE2-binding sites, while the receptor affinity was unaltered. The inhibitory effect of isoproterenol on [3H]PGE2 binding was already seen after 10 min of isoproterenol treatment, and the maximal effect was obtained after 30-60 min. Half-maximal inhibition of binding occurred at a concentration of 5 X 10(-8) M isoproterenol. The effect of isoproterenol could be mimicked by epinephrine, theophylline, and (Bu)2-cAMP, indicating that elevated levels of cAMP are the common mechanism by which these agents affect PGE2 binding. Furthermore, the isoproterenol-induced inhibition of PGE2 binding was completely blocked by propranolol. The effects of some FFA and indomethacin were studied on PGE2 receptor binding, too. From the results of the latter studies, we suggest that endogeneously released arachidonic acid could account for some of the reduction in PGE2 binding. In conclusion, a beta-adrenergic receptor-mediated cAMP-dependent mechanism for the regulation of PGE2 receptor binding is demonstrated in both human and rat adipocytes.

Adipose Tissue↗

PubMed1985

Decrease of prostaglandin E2 receptor binding is accompanied by reduced antilipolytic effects of prostaglandin E2 in isolated rat adipocytes.

The effect of treatment of isolated rat adipocytes with prostaglandin E2 (PGE2) on subsequent [3H]PGE2 binding was studied. In addition, the antilipolytic effects of was studied. In addition, the antilipolytic effects of PGE2, adenosine, and insulin were studied in control and PGE2-treated adipocytes. Treatment of adipocytes with PGE2 (1 microM) decreased the binding of [3H]PGE2 by 61% (from 11.0 to 4.6 fmol/10(6) cells, P less than 0.005). Scatchard analysis of the binding data demonstrated that the decrease of PGE2 receptor binding was due to a decrease in the apparent number of PGE2 receptors while the apparent receptor affinity was unaltered. Reduction of the PGE2 receptor binding was specifically regulated inasmuch as structurally related compounds such as PGF2 alpha and arachidonic acid had only minor effects on subsequent [3H]PGE2 receptor binding. Reduction of the available receptor number was associated with a significant decrease in the antilipolytic effect of PGE2 on the isoproterenol-stimulated lipolysis (P less than 0.05). The maximal antilipolytic effect of PGE2 was decreased by 45%. Desensitization of the biological effect of PGE2 (antilipolysis) was only partially specifically regulated inasmuch as the antilipolytic compound phenylisopropyladenosine also had reduced antilipolytic effect in PGE2-treated cells. However, the antilipolytic effect of insulin was similar in control and PGE2-treated cells. It was found that the PGE2-induced decrease of [3H]PGE2 receptor binding may be due to a very tight coupling between the PGE2 molecule and its specific receptor. This tight coupling may then represent an occupancy of the receptor rather than a true loss of receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1985

Insulin pump treatment: effect on glucose homeostasis, metabolites, hormones, insulin antibodies and quality of life.

Continuous subcutaneous insulin infusion (CSII) with a portable pump was compared to unchanged conventional treatment (UCT) in long-term treated patients with IDDM in order to evaluate changes in glucose homeostasis, metabolites, hormones and quality of life. We found that the mean blood glucose values, measured at home, and the HbA1c values were significantly lower in the CSII group compared to the UCT group. The improved control during CSII was followed by a nearly normalization of the diurnal pattern of FFA and ketone bodies in plasma. Plasma free insulin values were significantly higher in the morning (fasting) during CSII compared to UCT, whereas the mean diurnal concentrations and the diurnal pattern were identical in the 2 groups. Both peak values of growth hormone during the day and the fasting values were significantly lower in the CSII group compared to the UCT group. In patients treated with the insulin pump (CSII) the wellbeing (quality of life) was estimated to be significantly improved. Two patients developed ketoacidosis during CSII, whereas 2 controls (UCT) were hospitalized with hypoglycemic coma. We conclude that insulin pump treatment for 6 months results in a near normalization of glucose and FFA metabolism, resulting in an improved quality of life. The improved control seems not to be explained by a change of the diurnal pattern of plasma insulin. However, the higher morning values may be of significant importance.

Adult↗

PubMed1985

Characterisation of mechanisms responsible for uraemic insulin resistance: in vitro experiments.

In an attempt to define the cellular basis of the uraemic insulin resistance we studied insulin action in adipocytes from eight patients with undialysed chronic uraemia and from eight matched healthy controls. (125I)-insulin binding to fat cells from uraemic patients was normal. In contrast (14C)-D-glucose transport exhibited decreased sensitivity to insulin. The concentrations of insulin that elicited a half-maximal response were 422 +/- 95 pmol/L in uraemic patients and 179 +/- 38 pmol/L in normals (p less than 0.01). The non-insulin and the maximally insulin stimulated glucose transport of adipocytes from uraemic patients was normal. The lipogenesis of fat cells from uraemic patients had depressed sensitivity to insulin (half-maximal stimulation at 38 +/- 8 pmol/L in uraemic patients and at 11 +/- 3 pmol/L in normals, p less than 0.01) with unchanged non-insulin and maximally insulin stimulated lipogenesis. Taken together these results suggest that the insulin resistance of adipocytes from patients with chronic uraemia may be primarily accounted for by post-binding defects localised to glucose transport and metabolism.

Adipose Tissue↗

PubMed1984

Prostaglandin E2 receptor binding and action in human fat cells.

The prostaglandin E2 (PGE2) receptor in human adipocytes was identified by the use of [3H]PGE2. The receptor binding at physiological temperature and pH was specific, saturable, and slowly reversible. Half-maximal displacement for [3H]PGE2 binding occurred with 2.5 nmol/liter. Half-maximal inhibition of isoproterenol-induced lipolysis was achieved at a concentration of PGE2 of 3.8 nmol/liter and half-maximal inhibition of basal lipolysis was achieved at a concentration of PGE2 of 0.9 nmol/liter. The order of potency for prostaglandin inhibition of receptor binding and antilipolytic effect was the same, with PGE2 greater than PGF2 alpha much greater than arachidonic acid. Scatchard analysis of the binding data revealed a nonlinear plot indicating the existence of two or more binding sites with different affinities. The binding sites of high affinity had an equilibrium constant (Kd) of 2 nmol/liter and a total binding capacity of 58 fmol/10(6) adipocytes which corresponds to about 33,000 binding sites per adipocyte. The binding sites of low affinity had a Kd of 56 nmol/liter and a total binding capacity of 700 fmol/10(6) adipocytes. We conclude that [3H]PGE2 binds to receptors in isolated human adipocytes and that their antilipolytic effects are mediated by this binding.

Adipose Tissue↗

PubMed1984

Improved in vivo insulin effect during continuous subcutaneous insulin infusion in patients with IDDM.

It has recently been shown that conventionally treated IDDMs are insulin resistant. Using the insulin clamp technique, we studied the influence of metabolic status on the in vivo insulin effect in these patients. Eleven IDDMs, treated conventionally with diet and insulin for 10.7 +/- 5.6 yr, were studied before and after continuous subcutaneous insulin infusion (CSII) treatment (with a portable pump) for 6 mo. We found that conventionally treated diabetic subjects were extremely insulin resistant with regard to peripheral glucose uptake. Glucose uptake, at an insulin concentration of about 80 microU/ml, was 4.3 +/- 2.0 mg/kg X min before treatment compared with 11.5 +/- 4.0 mg/kg X min in normals (P less than 0.01). After pump treatment for 6 mo, metabolic control improved significantly (HbA1c decreased from 8.9 +/- 1.9% to 7.4 +/- 1.2%, P less than 0.01) and, parallel to that, glucose uptake increased about 80% to 7.5 +/- 3.5 mg/kg X min (P less than 0.01). The mean daily plasma FFA level decreased from 0.32 +/- 0.10 mmol/L to 0.21 +/- 0.07 mmol/L (P less than 0.01); this variable was negatively correlated to the glucose clearance rate (r = -0.62, P less than 0.01). There was no statistically significant change in mean daily plasma insulin and plasma growth hormone levels or in 24-h cortisol excretion in the urine (P greater than 0.1). The insulin binding capacity of serum IgG was also unchanged, and there was no significant relationship between this quantity and glucose clearance rates (r = 0.18, P greater than 0.1). We conclude that conventionally treated IDDMs are insulin resistant with regard to peripheral glucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗