Allergens displayed on virus-like particles are highly immunogenic but fail to activate human mast cells.

BACKGROUND: The goal of allergen-specific immunotherapy is the induction of protective immune responses in the absence of anaphylactic reactions. We have previously shown that Fel d 1, the major cat allergen, displayed in a repetitive fashion on virus-like particles (VLPs) may fulfill these criteria. Specifically, Fel d 1 on VLPs induced strongly increased protective IgG responses compared to free allergen in mice while anaphylactic reactions were essentially abolished. Here we extend these findings to human mast cells and offer a mechanistic explanation for the reduced anaphylactic activity. METHODS: We differentiated human mast cells in vitro from blood-derived stem cell progenitors and sensitized the cells with a monoclonal Fel d 1-specific IgE. We compared the capability of Fel d 1 to induce mast cell activation in its free form versus displayed on VLPs and we performed allergen binding studies by surface plasmon resonance as well as flow cytometry. RESULTS: We show that free Fel d 1 induces degranulation of IgE-sensitized mast cells whereas Fel d 1 displayed on VLPs fails to induce mast cell activation. We demonstrate that this inability to activate mast cells is based on a biophysical as well as a biochemical mechanism. Firstly, Fel d 1 on VLPs showed a strongly impaired ability to bind to surface-bound IgE. Secondly, despite residual binding, repetitively displayed allergen on VLPs failed to cause mast cell activation. CONCLUSION: These findings indicate that repetitively displaying allergens on VLPs increases their immunogenicity while reducing their potential to cause anaphylactic reactions by essentially eliminating IgE-mediated activation of mast cells.

Anthropometric, hormonal and biochemical differences in lean and obese women before and after menopause.

The menopausal status is associated with an increased risk of metabolic and cardiovascular diseases. Since the post-menopausal modifications have not been clearly investigated in obese women, we evaluated the influences of menopausal status on anthropometric, hormonal and biochemical characteristics in selected groups of normal-weight and obese women. We studied 92 female outpatients: 24 normal-weight pre-menopausal (Pre-NW) [body mass index (BMI) 23.6 +/- 0.48, age 44.8 +/- 0.68], 24 normal-weight post-menopausal (Post-NW) (BMI 23.7 +/- 0.44, age 55.5 +/- 0.69), 24 obese pre-menopausal (pre-OB) (BMI 32.3 +/- 0.45, age 44.6 +/- 0.75), 20 obese post-menopausal women (Post-OB) (BMI 32.9 +/- 0.57, age 55.2 +/- 0.82). All the subjects were non smokers and free from hypertension, diabetes or impaired glucose tolerance (IGT). Anthropometric parameters, body composition, 17 beta-estradiol, LH, FSH, androstenedione, SHBG, testosterone and leptin were determined. Free androgen index (FAI) and insulin resistance index (HOMA) were calculated. In comparison with Pre-OB, Post-OB had higher values of waist circumferences (p < 0.02), while Post-NW showed no difference. Total and LDL-cholesterol were high in Post-NW women, whereas in the obese subjects they were already elevated in the premenopausal period. SHBG levels declined and FAI increased in Post-OB in comparison with Pre-OB. SHBG levels showed an inverse correlation with BMI, waist and waist-to-hip ratio (WHR), while FAI positively correlated with waist values. Serum leptin levels were higher in Post-OB than in Pre-OB, whereas they were similar in normal-weight women. The rise of leptin levels may be related to the greater abdominal fat deposition. In addition, menopausal status of uncomplicated obese women is associated with a greater abdominal fat deposition and with higher values of free androgen index, which may be considered as factors of cardiovascular risk.

Relationship of visceral fat distribution to angiographically assessed coronary artery disease: results in subjects with or without diabetes or impaired glucose tolerance.

BACKGROUND AND AIM: To evaluate the relationship between the degree of coronary artery disease (CAD) and the amount of visceral fat deposition in a mixed population of CAD patients with or without diabetes or impaired glucose tolerance (IGT), and with different body weights. METHODS AND RESULTS: A total of 55 patients undergoing coronary angiography (43 men and 12 women with a mean age of 58.9 +/- 1.1 years, range 37-70, and a mean body mass index [BMI] of 27.9 +/- 0.4, range 21.3-38.7) were studied in order to establish whether the coronary damage exclusively depends on intra-abdominal adipose tissue per se, or may be influenced by the coexistence of diabetes or IGT. Twenty-one subjects were non-diabetic, 13 had type 2 diabetes, and 21 IGT. Hypertension was found in 47% and dyslipidemia in 55%; 69% were smokers. The angiographic evaluation of CAD was made using the method of Gensini, and computed tomography (CT) was used to estimate the amount of visceral adipose tissue (VAT) based on a single scan at L4 level. Clinical, anthropometric, biochemical and hormonal variables, as well as smoking and alcohol consumption were determined. In the study population as a whole, the coronary score did not correlate with VAT, but only with smoking. However, both univariate and multivariate regression analysis showed that CAD significantly correlated with VAT in the non-diabetic patients, particularly in those with VAT of > 130 cm2. This correlation did not appear in the diabetic or IGT patients, nor when the group of patients with VAT > 130 cm2 was extended to include diabetic or IGT patients. No relationship was found between CAD and BMI or the other considered variables. CONCLUSIONS: In a mixed population of CAD patients with or without diabetes, CAD correlates with VAT only in the absence of diabetes or IGT, and especially when VAT exceeds 130 cm2 at an L4 CT scan, regardless of weight or obesity. Diabetes or IGT therefore seem to contribute towards the development of CAD regardless of the amount of VAT.

QT dispersion in uncomplicated human obesity.

OBJECTIVE: Because obese patients generally may be prone to ventricular arrhythmias, this study was designed to measure the interval between Q- and T-waves of the electrocardiogram (QT) interval dispersion (QTD) in uncomplicated overweight and obese patients. QTD is an electrocardiographic parameter whose prolongation is thought to be predictive of the possibility of sudden death caused by ventricular arrhythmias. To better evaluate the association between obesity per se and QTD, the study population was intentionally selected because they were free of complications. RESEARCH METHODS AND PROCEDURES: QTD (defined as the difference between the maximum and the minimum QT corrected interval [QTc] across the 12-lead electrocardiogram) was measured manually in 54 obese patients (Group A: mean body mass index [BMI] of 38.1 +/- 0.9 kg/m2 [SEM], 15 males and 39 females), 35 overweight patients (Group B: mean BMI of 27.3 +/- 0.2 kg/m2, 10 males and 25 females), and 57 normal weight healthy control subjects (Group C: mean BMI of 21.9 +/- 0.2 kg/m2, 17 males and 40 females). The obese and overweight patients had no heart disease, hypertension, diabetes, or impaired glucose tolerance and did not have any hormonal, hepatic, renal or electrolyte disorders. The study subjects were matched in terms of age (mean age 38.4 +/- 1.2 years) and sex. RESULTS: The QTDs were comparable among the three groups: Group A, 56.4 +/- 2.6 ms; Group B, 56.7 +/- 2.1 ms; and Group C, 59.4 +/- 2.1 ms; not significant. The QTc intervals of Group A and Group B were similar to that of Group C (411.8 +/- 3.3, 407.2 +/- 3.9, and 410.3 +/- 3.9 ms, respectively [not significant]) and did not correlate with BMI. An association was found between QTD and QTc (r = 0.24, p < 0.005). Using multivariate stepwise regression analysis of the study population, QTD did not correlate with age, BMI, waist circumference, or abdominal sagittal diameter. DISCUSSION: These data suggest that QTD in uncomplicated obese or overweight subjects is comparable with that in age- and sex-matched normal weight healthy controls. In this study population, no association was found between QTD and anthropometric parameters reflecting body fat distribution.

Food-related sensory stimuli are able to promote pancreatic polypeptide elevation without evident cephalic phase insulin secretion in human obesity.

The data concerning the cephalic phase of insulin secretion (CPIS) in human obesity are controversial. We investigated the effect of a variety of sensory challenges on CPIS in 17 non-diabetic obese patients (four males, 13 females, mean age 41.1 years, mean BMI 38.7). Water, saccharin, and lemon juice were used as oral stimuli, and a complete meal was simply presented as visual and olfactory stimulations. Twelve healthy normal-weight subjects (four men, eight women, mean age 39.9, mean BMI 22.5) also underwent oral stimulation as controls, and the patients who underwent the sight and smell stimulations were also tested for pancreatic polypeptide (PP) changes in order to verify the occurrence of truly cephalic reflex during the test. Insulin levels were measured before and after each stimulation (every min for the first 5 min, and then after 10, 20, and 30 min). None of the stimuli (saccharin, lemon juice or water retained in the mouth for 2 min and were then spat out; the combined and separate sight and smell of a meal for 2 min) led to a significant increase in insulin in the obese patients (except in the case of one woman after oral stimulation). The oral stimuli led to a variable CPIS in one female and three male controls. Despite the absence of CPIS, the five obese patients undergoing all three sensory stimulations related to the meal (combined sight and smell, sight alone and smell alone) showed an early and significant increase in plasma PP concentrations within the first 3 min; this was more pronounced after the combined than after the separate exposure. Although only preliminary, these results underline the variability but substantial lack of CPIS in obese patients, thus suggesting that it can be considered a relatively rare and unrelevant event even in the presence of a true brain-mediated reflex revealed by the rapid and consistent increase in PP found in our experiments.

The compliance of hypocaloric diet in type 2 diabetic obese patients: a brief-term study.

In studies of the effect of diets in obese type 2 diabetic patients, information about the degree of compliance or non-compliance is generally lacking or incomplete, though their poor long-term success rate is widely recognized. We have quantified the degree of short-term compliance with a personalized hypocaloric diet (800-1500 kcal) in 77 obese type 2 diabetic patients (mean age 60, mean BMI 34.4) three months after explaining their dietary schedule and its expected advantages by means of simple but essential nutritional advice lasting about 20 minutes of the type currently used for such patients attending diabetes care institutions or outpatient departments. Even though a mean 14% reduction in daily food intake was achieved, the mean daily energy intake at the interview (assessed by means of the 3-day recall method) still exceeded the prescribed diet by 40-50%. The worst compliance in terms of total excess energy intake or carbohydrate and fat intake was found in the older patients. The greater the excess of food intake, the poorer the metabolic control, as expected.

The role of central fat distribution in coronary artery disease in obesity: comparison of nondiabetic obese, diabetic obese, and normal weight subjects.

OBJECTIVE: To investigate the degree of coronary artery disease (CAD) in relation to obesity and fat distribution in obese patients with normal glucose tolerance, in comparison with CAD of diabetic obese patients and of normal weight subjects with CAD. DESIGN: Patients listed for coronary angiography with different body mass index (BMI) with or without diabetes: study of the correlation between severity of coronary damage and fat distribution. SUBJECTS: 92 patients subdivided into: 30 normal glucose tolerant obese (BMI 31.7+/-0.5, aged 53+/-1.7 y), 28 type 2 diabetic obese (BMI 30.7+/-0. 3, aged 57+/-1.2 y), and 34 normal weight patients (BMI 23.1+/-0.3, aged 54+/-1.7 y). MEASUREMENTS: CAD assessed by angiography and evaluated according to the method of Gensini. Fat mass and fat distribution assessed by bioelectrical impedance and anthropometry. Clinical, biochemical and hormonal variables, as well as smoking habits and alcohol intake. RESULTS: The angiographic coronary scores were similar in nondiabetic obese and in diabetic obese patients, and were significantly higher than those of normal weight subjects. In the entire population coronary score correlated with indices of abdominal fat distribution. In the stepwise analysis of each group separately, waist hip ratio (WHR) correlated with coronary score only in normal weight nondiabetic patients. CAD was inversely associated with BMI only in nondiabetic obese patients. CONCLUSION: CAD of obese patients: 1) is similar to that of diabetic obese patients; 2) is more severe than that of normal weight individuals; and 3) is inversely correlated with BMI. CAD appears to be associated with WHR, not with BMI, only in nondiabetic patients with normal body weight. On the contrary, CAD of diabetic obese patients is unrelated to BMI and parameters of fat distribution, but is associated with smoking habits.

Diabetes and complications after cardiac surgery: comparison with a non-diabetic population.

Diabetes is a well-recognized independent risk factor for mortality due to coronary artery disease. When diabetic patients need cardiac surgery, either coronary-aortic by-pass (CABP) or valve operations (VO), the presence of diabetes represents an additional risk factor for these major surgical procedures. Because of controversial data on mortality rates and post-operative complications in diabetic patients, probably due to not exactly comparable groups of patients, this retrospective study aimed to compare two homogeneous populations, which were different only for the presence or absence of diabetes. We studied 700 patients undergoing cardiac surgery: 350 with and 350 without diabetes, mean age 62 +/- 9 years (67% males); 441 underwent CABP and 259 VO. Apart from the diabetes, the two groups were strictly matched for age, body mass index, concomitant pathologies and smoking habits, except for previous neurological injuries (more frequent in diabetic patients), and for a slightly lower ejection fraction in the diabetic group. Intra- and post-operative complications or events were evaluated carefully: death, number staying in post-operative intensive care unit (ICU), renal, hepatic and respiratory complications, necessity for reoperation and hemotransfusions. Anesthesia and surgical procedures (including extra-corporeal circulation techniques) remained substantially unchanged over the period of recruitment of patients (1996-1998) and applied equally to both groups of patients. All diabetic patients were treated with insulin by using standard procedures in order to optimize metabolic control. Diabetic patients in our study, did not show higher rates of mortality in comparison with non-diabetic patients, but had more total neurological complications, more renal complications, a higher re-opening rate, more prolonged ICU stay, and they needed more blood transfusions. Diabetes remains an independent risk factor for these events even in a multivariate logistic regression model analysis. In the subgroup of diabetic patients who underwent CABP a higher rate of renal dysfunction, re-opening, need for hemotransfusions and prolonged ICU stay were confirmed. In the subgroup of diabetic patients undergoing VO we found a higher rate of renal dysfunction, reopening, prolonged ICU stay and major lung complications. In conclusion, diabetes does not seem to increase the mortality rates of cardiac surgery, but diabetic patients undergoing CABP have, on the basis of the relative risk evaluation, a 5-fold risk for renal complications, a 3.5-fold risk for neurological dysfunction, a double risk of being hemotransfused, reoperated or being kept 3 or more days in the ICU in comparison with non-diabetic patients. Moreover, diabetic patients undergoing VO have a 5-fold risk of being affected by major lung complications.

Obesity and coronary artery surgery.

OBJECTIVE: To assess whether obesity is a risk factor for morbidity and mortality in patients undergoing elective coronary artery revascularization. DESIGN: Prospective, clinical study. SETTING: University hospital. PARTICIPANTS: Three hundred forty-five consecutive patients who underwent elective coronary revascularization with cardiopulmonary bypass and without associated procedures. INTERVENTIONS: Patients were assigned to the obese group if their body mass index was greater than 30 for men and 28.6 for women, according to the World Health Organization indications. MEASUREMENTS AND MAIN RESULTS: Preoperative and intraoperative variables were collected and checked for homogeneity of the groups. Postoperative outcome was assessed on the basis of intubation time, intensive care unit (ICU) and postoperative hospital stay, mortality rate, and incidence of transfusions, reoperations, low-output syndrome, minor and major neurologic dysfunction, minor and major lung dysfunctions, renal dysfunction, and superficial and deep infections. The effect of obesity on postoperative outcome was tested with a multivariate logistic regression analysis. Obese and control patients had the same intubation time and ICU and postoperative hospital stay. Mortality and all major complications occurred with the same incidence in the two groups. Obese patients had a significantly (p < 0.05) greater rate of superficial infections and more (24.1% v 7.4%; p < 0.001) minor lung complications. Conversely, they had a significantly lower transfusion rate (27.5% v42.7%; p < 0.01). CONCLUSION: Obese patients had only minor complications after coronary artery surgery. The large body surface area because of obesity protects them against the hemodilution-related transfusion risk.

Secondary failure of oral hypoglycaemic agents in lean patients with type 2 diabetes mellitus: insulin sensitivity, insulin response to different stimuli, and the role of cyclic-AMP.

The aim of this study was to evaluate the insulin (IRI) response to different stimuli and insulin sensitivity in Type 2 diabetic patients responsive to oral hypoglycaemic agents (OHA) and in Type 2 diabetic patients with secondary failure of OHA (SF), all patients being of normal body weight (relative body weight less than 120%), and the possible role of cyclic AMP in the reduced IRI release. SF patients, without islet cell antibodies (ICA), with hyperglycaemia lasting more than 3 months, underwent tests with i.v. tolbutamide (n = 21), i.v. glucose (n = 14), i.v. glucagon (n = 19), i.v. arginine infusion (n = 18); the arginine infusion was repeated in 12 patients during administration of aminophylline, an inhibitor of phosphodiesterase. The same tests were performed in groups of 8 to 15 OHA patients and in groups of 6 to 17 healthy subjects. During all the tests, blood glucose levels were higher in SF patients, than in OHA patients and in healthy subjects. Both SF patients and OHA patients had no IRI response to glucose; SF patients, in contrast to OHA patients, had a reduced IRI response to tolbutamide and to glucagon. The IRI response to arginine was not different in OHA, in SF patients and in healthy controls, but was significantly enhanced by aminophylline only in healthy controls. Insulin infusions (1.66 mU/Kg/min for 90 min) were performed in OHA patients and in SF patients at blood glucose levels of 150 and of 250 mg/dl: during the last 60 min, the amount of glucose metabolized (M), and the insulin sensitivity (M/I) index were greater in OHA than in SF patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Italian Consensus Conference--overweight, obesity and health.

On 5 and 6 April 1991, at the National Research Council (CNR) in Rome, a Consensus Conference on the relationship between overweight, obesity and health was held. The conference was sponsored by FATMA (Applied Project on Disease Factors of the CNR) and UICO (Italian Society for the Study of Obesity) with the purpose of establishing guidelines for health employees. The development of the conference followed the methodology set down by OMAR to obtain a rational and significant consensus on the answers to six basic questions prepared by the planning committee. The questions were the pivotal point of the conference and were brought to the attention of all the attendees and widely diffused among the medical community; they were proposed with the aim of giving an exhaustive definition of obesity, to investigate its relationship with mortality and morbidity, to highlight its social characterization, to indicate methods of evaluation and recommendations for weight loss, to select groups at risk, and to focus general guidelines for research. After the presentation of the state of the art on 18 topics by experts in the field, the 22 members of the consensus panel, impartial experts from a vast area of the scientific community, discussed a draft document representing the answers to the questions, which was subsequently submitted to the 307 attendees, discussed and then approved. This paper is the definitive document of the Consensus Conference. The introduction explains the reasons which led to the decision to promote the conference six years after the one held in the United States. The methodology is then set out. The questions are answered in the form of recommendations and backed up by data and scientific evidence from the literature.

Sleep-related growth hormone secretion in human obesity: effect of dietary treatment.

Eight obese patients (4 male, 4 female; mean age = 35.9 years) before [mean body mass index (BMI) = 37.1] and after (mean BMI = 31.4) weight loss by means of a mixed hypocaloric diet were compared with 8 lean subjects (4 male, 4 female; mean age = 37.1 years, mean BMI = 22.3) in a study of their nocturnal sleep patterns and sleep-related growth hormone (GH) secretions. Although no sleep disorders (in particular, sleep apnea and hypersomnia) were observed, GH secretion was markedly altered in obese patients that showed no sleep-related GH peaks. After weight loss, the sleep architecture in obese subjects was unchanged. On the contrary, GH peak appeared to be only partially restored and delayed until after stage III-IV of non-REM sleep. Our study on obese subjects suggests that the altered nocturnal GH secretion, probably related to a hypothalamic dysfunction, may be the result of the obesity per se.

[Italian Consensus Conference; overweight, obesity and health (ICC S.O.S. 1991)]. / Consensus Conference Italiana: sovrappeso, obesità e salute (CCI S.O.S. '91).

On April 5th and 6th 1991, at the National Research Council (CNR) in Rome, a Consensus Conference on the relationship between Overweight, Obesity and Health was held. The Conference was sponsored by FATMA (Applied Project on Disease Factors of the CNR) and UICO (Italian Society for the Study of Obesity) with the purpose of establishing guidelines for health employees. The development of the Conference followed the methodology set down by OMAR to obtain a rational and significant consensus on the answers to 6 basic questions prepared by the Planning Committee. The questions were the pivotal point of the Conference and were brought to the attention of all the attendees and widely diffused among the medical community; they were proposed with the aim of giving an exhaustive definition of obesity, to investigate its relationship with mortality and morbidity, to highlight its social characterization, to indicate methods of evaluation and recommendations for weight loss, to select groups at risk, and to focus general guidelines for research. After the presentation of the state of the art on 18 topics by experts in the field, the 22 members of the Consensus Panel, impartial experts from a vast area of the scientific community, discussed a draft document representing the answers to the questions, which was subsequently illustrated to the 307 attendees, discussed and then approved. This paper is the definitive document of the Consensus Conference. The introduction explains the reasons which led to the decision to promote the Conference six years after the one held in the United States. The methodology is then set out. The questions are answered in the form of recommendations and backed up by data and scientific demonstrations from the literature.

[Caloric intake and distribution of the main nutrients in a population of obese children]. / Introito calorico e ripartizione dei principali nutrienti in una popolazione infantile obesa.

Calorie intake and the main nutrient contents were assessed in a population of 152 obese (OB) children (86 M; 66 F; age 7-11) and 153 normal weight (NW) peers (87 M; 66 F). The following method was used: a) an interview using a food dictionary to assess food intake during the 2 days prior to the study and on one holiday: and b) a weekly questionnaire. The mean food intake of OB did not exceed that of NW, but on the contrary was lower (OB: 1812.9 +/- 39.6 kcal/die; NW: 1928.5 +/- 39.4 kcal/die; p less than 0.05). The population studied consumed approximately 50% of calories as carbohydrates (CHO), 35% as fats (F) and 15% as protein (P), and no difference was noted between OB and NW. The percentage of CHO was lower than that recommended by LARN, whereas the percentages of F and P were higher. A significant increase with age was noted in F and P intake as was a significant reduction of CO. 70% of OB and 80% of NW matched or exceeded the calorie intake recommended by LARN. 30% of OB and 24% of NW consumed 30% less than the daily calorie intake recommended by LARN.

Pharmacological interaction between tolbutamide and acetylsalicylic acid: study on insulin secretion in man.

This study has been planned to investigate some aspects of the interaction between acetylsalicylic acid (ASA) and tolbutamide on insulin secretion. In healthy subjects, oral administration of 3.2 g daily of ASA for 3 days significantly enhanced a) basal insulin levels (p less than 0.01), b) arginine-stimulated insulin secretion (25 g i.v. over 30 min) (p less than 0.01) and c) tolbutamide-stimulated insulin secretion (1 g or 0.25 g i.v. as a bolus) (areas under curves: p less than 0.02). Corresponding decreases in glycemia were observed. Tolbutamide binding to serum proteins was significantly reduced after ASA treatment (p less than 0.02). We conclude that, in case of tolbutamide test, interferences between ASA and tolbutamide on insulin secretion might be dependent, at least in part, on enhancement of free-tolbutamide percentage in plasma and not only on a direct or synergic action of ASA on pancreatic B-cell. Therefore, acute stimulation of insulin secretion by tolbutamide appears not to be completely comparable to other traditional stimuli, when ASA effects are studied.

[Possible correlations between protein-loosing nephropathy and obesity]. / Possibili correlazioni tra nefropatia protido-disperdente ed obesità.

Nephrotic syndrome has been reported in obesity; its precise incidence in obese patients without diabetes mellitus and/or arterial hypertension is however unknown. Thirty-two obese subjects without complications were therefore assessed before and after weight loss, together with 18 healthy control subjects. Overnight albumin excretion rate (AER) was assessed using a RIA method (H. Albumin-Kit, Sclavo). Glomerular filtration rate (GFR) was also evaluated in 10 obese subjects using Cr51 before and after weight loss. AER was found to be higher, although the difference was not statistically significant, in obese subjects compared to controls, but was significantly reduced after weight loss (p = 0.05). GFR also showed a non-significant tendency to decrease following loss of weight. Systolic and diastolic blood pressures were significantly decreased following weight loss (p less than 0.01 and p less than 0.025 respectively). In conclusion, although it is not possible to confirm the presence of true nephropathy in uncomplicated obesity, the latter can facilitate the onset of hemodynamic-type mechanisms which, in the presence of diabetes mellitus or arterial hypertension, may lead to the appearance of the nephrotic syndrome.

Effect of acute administration of metoclopramide on insulin secretion in man.

The effect of acute i.v. administration of 2.5 mg metoclopramide (MCP), an antidopaminergic agent with low serotoninergic activity, on blood insulin and glucose concentrations was studied in 9 healthy men. MCP was able to significantly decrease basal serum insulin levels (from 6.8 +/- 1.1 to 4.3 +/- 0.7 microU/ml in 120 min; p less than 0.025) with a parallel elevation in blood glucose (from 72.5 +/- 1.1 to 82.6 +/- 2.5 mg/dl in 120 min; p less than 0.01). These findings, which were not observed after placebo, and appeared not to be explained by the spontaneous occurrence of physiological oscillations of insulin and glucose plasma levels, are consistent with similar effects observed after administration of other antidopaminergic agents and with the stimulatory activity on insulin and glucagon release described during dopamine infusion in man.

Basal and norepinephrine-stimulated lipolysis in differently sized human isolated adipocytes: comparison of three modalities for results expression.

Lipolytic rate in basal conditions and after adrenergic stimulation with norepinephrine (NE, 8.87 microM) from suspensions of differently sized human adipocytes has been tested. Adipocytes were intra surgically provide for obese (OB) and normal-weight (NW) individuals. Total volume of cells was constant in all samples, being 4% in the incubation system. Glycerol released in the buffer at the end of one hour incubation was measured and results expressed by three different features, i.e. related to: A) total volume of cells (nmol glycerol/40 microliters/h); B) cell number (nmol/cell x 10(4)/h), or C) cell surface unit (nmol/mm2/h). No statistically significant differences between OB and NW have been found, nor between histometrical parameters or between lipolytic rates. A positive, significant correlation between lipolytic rate B and Mean Cell Volume (MCV) or total Cell Surface (TCS 10(4)) has been found (rs from 0.90 to 0.94, p less than 0.01) both in basal conditions and after stimulation. A significant, positive correlation between stimulated lipolytic rate C and MCV (r = 0.67, p less than 0.05) has also been observed. Our results suggest that lipolytic rate appears to be correlated to cell volume. While the expression of lipolytic rate with relation to total volume of cells in the sample (rate A) may be more convenient to minimize the effect of different size of cells in different samples, data expressed as glycerol released per number of cells (rate B) or per surface unit (rate C) appears however to be more suitable form main experimental purposes in metabolic studies of adipocytes.