Search PubMed⌕ Search

Biomedical subjects

R Giorgino

Publications and source records attributed to R Giorgino.

At least 73 records · Page 4Linked to original sources
PubMed1992

High systolic blood pressure increases prevalence and severity of retinopathy in NIDDM patients.

OBJECTIVE: To determine whether the severity of retinopathy is higher in a group of NIDDM patients with sBP greater than or equal to 140 mmHg compared with NIDDM patients with sBP less than 140 mmHg. RESEARCH DESIGN AND METHODS: Ophthalmoscopy and FAG were conducted among a group of NIDDM patients with either a sBP above (n = 54) or below (n = 55) 140 mmHg. The groups were matched according to diabetes duration, metabolic control (HbA1c), and AER. RESULTS: Patients with sBP greater than 140 mmHg had a higher prevalence of retinopathy, as established according to a rating scale (4.9 +/- 3.8 vs. 3.2 +/- 3.3, P less than 0.02); furthermore, their BMI values were higher (28.1 +/- 4.5 vs. 24.9 +/- 4.1 kg/m2, P less than 0.001). The group of normotensive subjects showed the highest rate of low grading (0-2) values. However, the highest prevalence rates of 8-10 grading values (proliferative retinopathy) were found in the hypertensive group. CONCLUSIONS: These data suggest that sBP values greater than or equal to 140 mmHg favor the onset of retinopathy in NIDDM patients during their 1st 10 yr of disease.

Blood Pressure↗
PubMed1991

Phorbol esters do not influence the maturation and the beta-adrenergic responsiveness of differentiated adipose precursor cells, cultured in a charcoal-treated serum medium.

Phorbol esters are a well defined group of tumor-promoting substances, which influence the proliferation, the differentiation and the hormonal responsiveness of a wide variety of cell types through the activation of protein-kinase C. Opposite effects have been described on the beta-adrenoceptors and the adenylate cyclase activity, depending on the cell type. Since there is no information about the influence of these substances on lipolysis in adipose precursor cells, the aim of the present study was to examine the effect of 7 days exposure to phorbol esters on the differentiation and the lipolytic responsiveness of rat preadipocytes, cultured in 10% charcoal-treated fetal calf serum. Our results demonstrate that prolonged exposure to these tumor promoters does not influence the differentiation, the beta-adrenoceptors number and the lipolytic response to adenylate cyclase or beta-adrenergic agonists in differentiated cells.

Adenylyl Cyclases↗
PubMed1991

Low dehydroepiandrosterone circulating levels in premenopausal obese women with very high body mass index.

Dehydroepiandrosterone (DHEA) has an anti-obesity effect in rodents and reduces body fat in normal men. Therefore, the plasma levels of DHEA were evaluated in nine premenopausal healthy women and in 13 menstrually active nondiabetic obese women, including patients (n = 6) with body mass index (BMI) over 40. In the obese group, a significant inverse correlation between DHEA levels and BMI was found. These results suggest that patients with severe obesity are unable to increase the DHEA adrenal production rate in order to parallel the increase in the hormone metabolic clearance rate (due to enlargement of body fat mass per se). The deficiency of this mechanism might itself contribute to the progressive fat accumulation in severe obesity.

Abdomen↗
PubMed1991

Is plasma 5 alpha-androstane 3 alpha, 17 beta-diol glucuronide a biochemical marker of hirsutism in women?

We investigated whether plasma androstanediol glucuronide (ADG) levels reflect the increased androgenicity in women with idiopathic hirsutism (n = 24) or hirsutism associated with polycystic ovary syndrome (n = 10). We also evaluated whether ADG levels parallel the clinical evolution of the hirsutism during a combined treatment, with cyproteroneacetate (2 mg) and ethinylestradiol (35 micrograms), of women with moderate idiopathic hirsutism. Finally, we investigated if there is evidence for increased conversion of precursors to ADG in hirsutism, by comparing the ADG levels, measured by RIA, to ADG levels obtained by applying the conversion rates of precursors obtained in non-hirsute women. ADG levels were increased in less than half of the patients with mild hirsutism. The clinical cure of hirsutism, which was obtained by the treatment in majority of patients, was accompanied by a significant decrease of plasma ADG levels, but a similar decrease was also observed in the 5 patients who did not respond to treatment. The data show that, although there is evidence for increased conversion of precursors to plasma ADG in mildly hirsute women, the latter is not a reliable parameter of androgenicity. Our data suggest, moreover, that treatment with cyproterone acetate and ethinylestradiol decreases 5 alpha-reductase activity, as indicated by the more important decrease in ADG levels than in the precursors.

Adult↗
PubMed1991

Insulin resistance and hypoglycemia in a patient with systemic lupus erythematosus: description of antiinsulin receptor antibodies that enhance insulin binding and inhibit insulin action.

We studied a patient with systemic lupus erythematosus and type B insulin resistance, who progressed from extreme insulin resistance to fasting hypoglycemia. The plasma insulin level was 63.3 +/- 20.9 pmol/L in the fasting state and rose above 1440 pmol/L postprandially. Intravenous administration of human insulin caused almost no decline in plasma glucose. Therefore, it was concluded that the patient was still resistant to insulin and that plasma insulin did not play a crucial role in the development of hypoglycemia. Immunoglobulin G from this patient did not inhibit insulin binding to the insulin receptor; rather, it enhanced [125I]insulin binding in both the immunoprecipitate and the in vitro binding assay to intact cells. Antiinsulin receptor antibodies strongly inhibited insulin internalization in human adipocytes, slowed down the dissociation of [125I]insulin from receptors and failed to induce down-regulation of surface insulin receptors in both the presence and absence of insulin. Finally, autoantibodies mimicked the insulin stimulatory effect on human fat cell lipogenesis even after long term exposure, but inhibited the metabolic potency of insulin when added simultaneously with the natural ligand. We conclude that antiinsulin receptor antibodies induce fasting hypoglycemia, through their continuous receptor stimulatory action, and insulin resistance, possibly by a conformational perturbation of the receptor protein, which, in turn, uncouples insulin receptor binding from receptor function.

Antibodies↗
PubMed1991

Inverse relationship between cortisol excretion rate and plasminogen activator inhibitor-1 (PAI-1) antigen and activity in premenopausal obese women.

The present study was undertaken in order to investigate the possibility of a relationship between plasminogen activator inhibitor-1 (PAI-1) and cortisol excretion rate in 15 obese women. We found a highly significant linear inverse correlation between cortisol excretion rate and both PAI-1 antigen (r = 0.79, P less than 0.001) and activity (r = 0.77, P less than 0.001). In addition, stepwise regression analysis showed that cortisol excretion rate maintained a strong negative relationship with PAI-1 antigen (significance level 0.03) and activity (significance level 0.003), when adjusted for other variables taken in examination (waist to hip ratio, body mass index, insulin, DHEAS, age). Even though this study only demonstrates a negative correlation, the possibility of a direct inhibitory effect of cortisol on PAI-1 production should be considered. In conclusion, the present study demonstrates an inverse correlation between cortisol excretion rate and PAI-1 antigen and activity, suggesting a possible role for cortisol in protecting obese women from reduced fibrinolytic activity.

Adult↗
PubMed1990

Up-regulation of androgen receptor binding in male rat fat pad adipose precursor cells exposed to testosterone: study in a whole cell assay system.

Binding of androgens to adipocytes has previously been evaluated using cytosol fractions without taking into account nuclear binding, although the latter is suggested to be close to the physiological site of action. In the present study, performed in differentiated fat pad adipose precursor cells, we describe a simple, reliable and reproducible androgen binding assay in a system with intact cells. Tritiated and unlabeled methyltrienolone (R1881) were used to define specific and unspecific androgen binding. Triamcinolone acetonide was added to prevent the binding of R1881 to other types of receptors. Differentiated adipose precursor cells contain a homogeneous class of high affinity androgen binding sites, and binding is saturable and reversible. Binding apparently occurs at one site, with a Kd in the range of physiological androgen concentration (about 4 nM). Competition studies indicate that the receptor is specific for R1881, testosterone and dihydrotestosterone, which have approximately the same affinity, while progesterone, estradiol and dexamethasone show much lower affinity. Androgen binding was markedly enhanced after cellular exposure to R1881 and testosterone but not dihydrotestosterone, and this increase was dependent on protein synthesis, suggesting the formation of new receptors by these androgens. In conclusion, fully differentiated adipocytes contain a specific, high affinity receptor, the density of which is dependent on androgens.

Adipose Tissue↗
PubMed1990

Extreme insulin resistance due to anti-insulin receptor antibodies: a direct demonstration of autoantibody secretion by peripheral lymphocytes.

A 59-year-old woman with systemic lupus erythematosus was found to have marked hyperglycemia, extreme insulin resistance and abnormally high plasma immunoreactive insulin. Her circulating erythrocytes displayed a dramatic decrease of 125I-labeled insulin binding. Both the whole serum and purified IgG fraction strongly inhibited the binding of radiolabeled insulin to control erythrocytes. These results suggested, although indirectly, the existence of antibodies to insulin receptors in the serum of the patient. To directly investigate this issue, we used an enzyme-linked solid-phase immunoassay which allows the detection and enumeration of lymphocytes secreting antibodies towards insulin receptors. Peroxidase-conjugated anti-human immunoglobulin is used to reveal the binding of antibodies to insulin receptor-coated dishes. We demonstrated that the patient's mononuclear cells, when briefly incubated in Petri dishes with partially purified insulin receptor, were able to secrete immunoglobulins of G class specifically directed to the antigen. Moreover, only a fraction of the whole population of anti-insulin receptor antibodies was directed towards the insulin binding region of the receptor, seemingly corresponding to the auto-antibodies detected with conventional binding-inhibition assay.

Antibody-Producing Cells↗
PubMed1990

D-(-)-beta-hydroxybutyrate inhibits catecholamine-stimulated lipolysis and decreases beta-adrenoceptors' affinity in human fat cells but not in lymphomonocytes.

The effect of D-(-)-beta-hydroxybutyrate, at concentrations commonly achieved during ketoacidosis in humans (10 mmol/l), on human fat cell lipolysis in vitro was the aim of this study. The basal lipolysis was not modified and beta-hydroxybutyrate did not affect forskolin- or dibutyryl-cAMP-stimulated glycerol release, whereas it markedly inhibited isoproterenol-stimulated lipolysis. In membranes of intact adipocytes exposed to D-(-)-beta-hydroxybutyrate for 1 h, we found a decrease in beta-adrenoceptor affinity in saturation experiments and a shift to the right of the isoproterenol-mediated radioligand [( 125I]-cyanopindolol) displacement curve. These findings suggest that beta-hydroxybutyrate inhibits catecholamine-stimulated lipolysis by decreasing beta-adrenoceptor affinity. No effect of beta-hydroxybutyrate was found on beta-adrenoceptor binding of intact mononuclear cells of peripheral blood. In conclusion, the beta-adrenoceptor affinity lowering effect of beta-hydroxybutyrate is seemingly specific to human fat cells and might represent a feed-back mechanism that prevents an uncontrolled breakdown of triglycerides and indirectly regulates its own production rate.

3-Hydroxybutyric Acid↗
PubMed1990

Testosterone treatment of ovariectomized rats: effects on lipolysis regulation in adipocytes.

The effects of testosterone treatment (2 mg every 14 days, for three months) on adipocyte lipolysis of intact (250-300 g body weight) and ovariectomized female rats were studied. Testosterone treatment of intact rats had no effect. Ovariectomy was followed by an increase in fat cell size and a decrease of lipolysis stimulated by isoproterenol, norepinephrine, epinephrine, forskolin, cAMP and isobutylmethylxantine. The number of beta-adrenergic receptors was reduced. There was, however, no change in the antilipolytic effects of UK 14,304 (alpha 2-adrenergic agonist), nicotinic acid, N6-phenylisopropyladenosine or insulin. Testosterone treatment of ovariectomized rats restored the number of beta-adrenoceptors and lipolysis stimulated by cAMP and isobutylmethylxantine, but not lipolysis stimulated by catecholamines and forskolin, suggesting a remaining defect in the catalytic unit of adenylate cyclase. These results indicate that ovariectomy is followed by a profound derangement of the lipolytic pathway at several levels, from beta-adrenoceptors number to the triglyceride lipase activity. This is partially restored by treatment with testosterone, which, however, has no effect on intact female rats. This study emphasizes the importance of ovarian integrity for the lipolytic regulation and the inability of testosterone to replace ovarian function in this regard or to affect lipolysis in intact female rats.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Changes in overall plasma norepinephrine turnover and lymphomonocyte beta-adrenoceptor number during combined caloric and sodium restriction in normotensive obese subjects.

The aim of the study was to evaluate in eight normotensive obese patients the influence of low sodium intake (9 mEq/day) on the sympathetic activity modifications induced by caloric restriction (2511 kJ/day). As compared to the isocaloric salt balanced diet, 7 days of normosodic underfeeding induced a decrease in the overall norepinephrine turnover (clearance and appearance rate) and 24 hours urinary output, whereas the combined caloric and salt restriction significantly increased the norepinephrine appearance rate and even more the norepinephrine clearance but, on the other hand, decreased the beta-adrenergic receptor number on the lymphomonocyte surface, suggesting a reduced peripheral sensitivity to catecholamines. Therefore, the utility of the combined sodium and caloric restriction in the treatment of the normotensive obese patients remains still questionable.

Adolescent↗
PubMed1989

Precursors of plasma androstanediol- and androgen-glucuronides in women.

Although androstanediol (AD) and androstanediolglucuronide (ADG) are generally considered to be parameters of peripheral androgen action, their plasma levels do not always vary in parallel, suggesting that they may have different precursors. Few hard data being available concerning ADG precursors in women, we studied in postmenopausal women with absent or suppressed adrenal function, the blood conversion rates of testosterone (T), dihydrotestosterone (DHT), androstenedione (A) and dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) to AD and ADG respectively, as well as the conversion of AD to ADG. Moreover conversions of these precursors to testosteroneglucuronide (TG) and dihydrotestosteroneglucuronide (DHTG), respectively, were also studied. Our data show that, whereas plasma A and DHT are the major precursors of AD, plasma DHEAS and A are the major precursors of plasma ADG, accounting for 50 and 15%, respectively, of plasma ADG, A being the major precursor of plasma TG and DHTG, respectively. When the conversion rates, obtained in this study, were applied to the plasma concentration of precursors found in normal young and postmenopausal women, respectively, the calculated concentration of product steroids accounted for almost the totality of the actual plasma levels of ADG, TG and DHTG respectively. The difference in relative importance of their precursors, explains that plasma concentrations of AD and ADG do not always vary in parallel; moreover, the importance of DHEAS as precursor of ADG explains the suppression by dexamethasone and the increase after adrenocortical stimulation of plasma ADG levels.

Adult↗
PubMed1989

2,3-diphosphoglycerate in normal and pathologic pregnancy: relationship to neonatal weight.

2,3-Diphosphoglycerate levels were assayed in 154 pregnant women in third trimester (61 normal, 52 diabetic, 19 with gestational hypertension, 7 with fetal macrosomia, and 15 with idiopathic fetal underdevelopment). A correlation was found between 2,3-diphosphoglycerate levels and birth weight (absolute and relative birth weight or birth weight expressed as percentile), which was negative in normal patients evaluated in the last 7 days before delivery (r = 0.38; p = 0.04) and positive in diabetic patients (evaluated in the third trimester and in the last 7 days before delivery) and in patients with gestational hypertension (evaluated in the third trimester) (r and p values differ according to whether birth weight is expressed as absolute, relative, or a percentile). No correlation was found between 2,3-diphosphoglycerate levels and birth weight in patients with neonatal underdevelopment or macrosomia of unknown origin. On the basis of these results we hypothesize that in some conditions the fetus can influence maternal 2,3-diphosphoglycerate levels and hence its own oxygen supply and growth in utero.

2,3-Diphosphoglycerate↗
PubMed1989

Influence of lactate on isoproterenol-induced lipolysis and beta-adrenoceptors distribution in human fat cells.

The influence of lactate on human adipocytes lipolysis and the possible relationship between lactate-induced metabolic effects and beta-adrenoceptor binding sites were investigated. beta-sites were identified in membranes with (125I)-cyanopindolol and in intact cells with (125I)-cyanopindolol and (3H)-CGP 12177. Lactate reduced isoproterenol-induced lipolysis in a dose-response fashion and such inhibition became significant only at 16 mmol/l lactate. Exposure of human fat cells to 16 mmol/l lactate significantly reduced beta-adrenoceptors density on crude membranes. When the binding assay was performed on intact cells using (125I)-cyanopindolol at 37 degrees C, the radioligand identified the same number of receptors, regardless of the presence of lactate in the preincubation medium. When (3H)-CGP 12177 was used, it bound to about 35% less receptors in lactate pre-treated cells than in control. Seemingly, at 37 degrees C, because of its lipophilicity, (125I)-cyanopindolol can cross the plasma membrane and bind to intracellular sites whereas, (3H)-CGP 1277, due to its hydrophilicity, identifies surface receptors only. Thus, the present in vitro study provides evidence that high levels of lactate, similar to the concentrations usually achieved in overt lactic acidosis, are able per se to inhibit human lipolysis and to redistribute beta-adrenoceptors from cell surface to a domain not accessible to hydrophilic ligands.

Adipose Tissue↗
PubMed1989

Biophysical and endocrine-metabolic changes during menopausal hot flashes: increase in plasma free fatty acid and norepinephrine levels.

Thermocutaneous, vascular, metabolic and hormonal changes were investigated during 11 hot flashes from 6 postmenopausal women. The first detectable change was an increase in finger blood flow with a concomitant enhancement of skin conductance. The increase in skin conductance was followed rapidly by a sharp rise in finger temperature. The main endocrine-metabolic changes associated with the above phenomena were a sharp increase in plasma free fatty acids (approximately 65%), norepinephrine (approximately 100%) and LH (approximately 20%) levels. Plasma glucose and cortisol tended to be increased but did not reach statistical significance; on the other hand, plasma insulin, glucagon, growth hormone, epinephrine and dopamine remained unchanged.

Adult↗