Different moderators of cognitive-behavioral therapy on subjective and objective binge eating in bulimia nervosa and binge eating disorder: a three-year follow-up study.

BACKGROUND: Different studies considered the mechanisms involved in the maintenance of binge eating in bulimia nervosa (BN) and binge eating disorder (BED), suggesting different pathways. The present 3-year follow-up study evaluated the relationships between psychopathological variables, and objective and subjective binge eating episodes in the two syndromes. METHODS: 85 BN and 133 BED patients were studied. Objective and subjective binge eating, and psychopathological data were collected in a face-to-face interview, and by means of different self-reported questionnaires. The same assessment was repeated at baseline (T0), at the end of an individual cognitive-behavioral treatment (T1), and 3 years after the end of treatment (T2). RESULTS: At baseline, BN and BED patients showed different emotions associated with binge eating: anger/frustration for BN and depression for BED patients. Objective binge eating frequency reduction across time was associated with lower impulsivity and shape concern in BN patients, and with lower emotional eating and depressive symptoms in BED patients. Lower subjective binge eating frequency at baseline predicted recovery, in both BN and BED patients. Recovery was associated with lower impulsivity and body shape concern at baseline for BN patients, and lower depression and emotional eating for BED patients. CONCLUSIONS: Eating psychopathology, psychiatric comorbidity, impulsivity and emotional eating have a different pattern of association with objective and subjective binge eating in BN and BED patients, and they act as different moderators of treatment. A different target of intervention for these two syndromes might be taken into account, and subjective binge eating deserves an accurate assessment.

Ezetimibe + simvastatin versus doubling the dose of simvastatin in high cardiovascular risk diabetics: a multicenter, randomized trial (the LEAD study).

BACKGROUND: The primary goal of therapy in patients with hypercholesterolemia and coronary heart disease (CHD) is reducing low-density lipoprotein cholesterol (LDL-C). This was a multicenter, randomized, double-blind, double-dummy study in patients with type 2 diabetes mellitus (T2DM). METHODS: Adult patients with T2DM and CHD (N = 93) on a stable dose of simvastatin 20 mg with LDL-C >or= 2.6 mmol/L (100 mg/dL) and

Sexual function in obese women with and without binge eating disorder.

INTRODUCTION: Binge eating disorder (BED) is highly prevalent among individuals seeking treatment for obesity. No controlled studies assessing the sexual functioning of these patients have been published so far. AIM: To investigate the sexual functioning of a clinical sample of obese women affected by BED, comparing them with obese non-BED patients (Ob), and with normal weight controls. METHODS: A consecutive series of 107 obese BED and 110 obese non-BED patients referring for the first time to the Clinic for Obesity of the University of Florence, together with a control group of 92 normal weight subjects, were studied. MAIN OUTCOME MEASURES: Patients were studied by means of the Structured Clinical Interview for DSM-IV and the Female Sexual Function Index (FSFI). Moreover, several self-reported questionnaires assessing the eating specific and general psychopathology were used. RESULTS: BED and obese non-BED probands reported a lower sexual activity compared to controls, in terms of absence of sexual intercourse rate, and sexual intercourse frequency. BED patients showed lower FSFI total and subscales scores compared to Ob, and Ob probands reported lower scores compared to controls. According to the multiple linear regression analysis, emotional eating was the main determinant of FSFI scores (FSFI total score, desire, arousal, lubrication, orgasm, satisfaction) for both BED and Ob patients, while impulsivity (inversely associated with FSFI total, orgasm, and pain) and shape concern (inversely associated with arousal, lubrication, orgasm) were main determinants for BED patients only. CONCLUSIONS: BED patients, compared to obese non-BED and controls, have worse sexual functioning, which is associated with high levels of emotional eating, impulsivity, and shape concerns. The relationship between sexual functioning and eating psychopathology should be carefully addressed in obese patients with and without BED.

Is obesity a further cardiovascular risk factor in patients with erectile dysfunction?

INTRODUCTION: Erectile dysfunction (ED) and, in particular, arteriogenic ED have been proposed as new markers of risk for incident major adverse cardiovascular events (MACE). Reduced penile blood flow is more common in obese people than in leaner ED subjects. AIM: To explore the interaction of overweight/obesity and penile blood flow in the prediction of incident MACE. METHODS: This is an observational prospective cohort study evaluating a consecutive series of 1,687 patients attending our andrological unit for ED. Different clinical, biochemical, and instrumental (penile flow at color Doppler ultrasound: PCDU) parameters were evaluated. MAIN OUTCOMES MEASURES: According to body mass index (BMI), subjects were divided into three groups: normal weight (BMI = 18.5-24.9 kg/m(2)), overweight (BMI = 25.0-29.9 kg/m(2)), and obese (BMI >or= 30.0 kg/m(2)). Information on MACE was obtained through the City of Florence Registry Office. RESULTS: Among patients studied, 39.8% were normal weight, while 44.1% and 16.1% showed BMI 25-29.9 and 30 kg/m(2) or higher, respectively. During a mean follow-up of 4.3 +/- 2.6 years, 139 MACE, 15 of which were fatal, were observed. Cox regression model, after adjusting for age and Chronic Diseases Score, showed that obesity classes along with the presence of arteriogenic ED (peak systolic velocity at PCDU <25 cm/second) were significantly and independently associated with incident MACE (hazard ratio = 1.47 [1.1-1.95], P < 0.05 and 2.58 [1.28-5.09], P < 0.001, respectively). When a separate analysis was performed for classes of obesity, reduced peak systolic velocity at PCDU (<25 cm/second) was significantly associated with incident MACE in obese (BMI >or= 30 kg/m(2)), but not in leaner, subjects. CONCLUSIONS: In obese subjects, more than in leaner ED subjects, impaired penile blood flow is associated with an increased risk of incident cardiovascular disease. The interaction with concomitant risk factors, such as obesity, should be taken into account when assessing the predictive value of penile blood flow for cardiovascular diseases.

Clinical and psychological correlates of health-related quality of life in obese patients.

BACKGROUND: Health-related quality of life (HRQL) is poor in obese subjects and is a relevant outcome in intervention studies. We aimed to determine factors associated with poor HRQL in obese patients seeking weight loss in medical units, outside specific research projects. METHODS: HRQL, together with a number of demographic and clinical parameters, was studied with generic (SF-36, PGWB) and disease-specific (ORWELL-97) questionnaires in an unselected sample of 1,886 (1,494 women; 392 men) obese (BMI > 30 kg/m2) patients aged 20-65 years attending 25 medical units scattered throughout Italy. The clinics provide weight loss treatment using different programs. General psychopathology (SCL-90 questionnaire), the presence of binge eating (Binge Eating scale), previous weight cycling and somatic comorbidity (Charlson's index) were also determined. Scores on SF-36 and PGWB were compared with Italian population norms, and their association with putative determinants of HRQL after adjustment for confounders was assessed through logistic regression analysis. RESULTS: HRQL scores were significantly lower in women than in men. A greater impairment of quality of life was observed in relation to increasing BMI class, concurrent psychopathology, associated somatic diseases, binge eating, and weight cycling. In multivariate analysis, psychopathology (presence of previously-diagnosed mental disorders and/or elevated scores on SCL-90) was associated with lower HRQL scores on both psychosocial and somatic domains; somatic diseases and higher BMI, after adjustment for confounders, were associated with impairment of physical domains, while binge eating and weight cycling appeared to affect psychosocial domains only. CONCLUSIONS: Psychopathological disturbances are the most relevant factors associated with poor HRQL in obese patients, affecting not only psychosocial, but also physical domains, largely independent of the severity of obesity. Psychological/psychiatric interventions are essential for a comprehensive treatment of obesity, and to improve treatment outcome and to reduce the burden of disease.

Ezetimibe/simvastatin vs simvastatin in coronary heart disease patients with or without diabetes.

BACKGROUND: Treatment guidelines recommend LDL-C as the primary target of therapy in patients with hypercholesterolemia. Moreover, combination therapies with lipid-lowering drugs that have different mechanisms of action are recommended when it is not possible to attain LDL-C targets with statin monotherapy. Understanding which treatment or patient-related factors are associated with attaining a target may be clinically relevant. METHODS: Data were pooled from two multicenter, randomized, double-blind studies. After stabilization on simvastatin 20 mg, patients with coronary heart disease (CHD) alone and/or type 2 diabetes mellitus (T2DM) were randomized to ezetimibe 10 mg/simvastatin 20 mg (EZ/Simva) or simvastatin 40 mg. The change from baseline in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio, triglycerides, and the proportion of patients achieving LDL-C < 2.6 mmol/L (100 mg/dL) after 6 weeks of treatment were assessed, and factors significantly correlated with the probability of achieving LDL-C < 2.6 mmol/L in a population of high cardiovascular risk Italian patients were identified. A stepwise logistic regression model was conducted with LDL-C < 2.6 mmol/L at endpoint as the dependent variable and study, treatment, gender, age (> or = 65 years or < 65 years), as independent variables and baseline LDL-C (both as continuous and discrete variable). RESULTS: EZ/Simva treatment (N = 93) resulted in significantly greater reductions in LDL-C, TC, and TC/HDL-C ratio and higher attainment of LDL-C < 2.6 mmol/L vs doubling the simvastatin dose to 40 mg (N = 106). Study [including diabetic patients (OR = 2.9, p = 0.003)], EZ/Simva treatment (OR = 6.1, p < 0.001), and lower baseline LDL-C (OR = 0.9, p = 0.001) were significant positive predictors of LDL-C target achievement. When baseline LDL-C was expressed as a discrete variable, the odds of achieving LDL-C < 2.6 mmol/L was 4.8 in favor of EZ/Simva compared with Simva 40 mg (p < 0.001), regardless of baseline LDL-C level. CONCLUSION: EZ/Simva is an effective therapeutic option for patients who have not achieved recommended LDL-C treatment targets with simvastatin 20 mg monotherapy. TRIAL REGISTRATION: Clinical trial registration numbers: NCT00423488 and NCT00423579.

Liver enzymes and risk of diabetes and cardiovascular disease: results of the Firenze Bagno a Ripoli (FIBAR) study.

The aim of the study was to assess gamma-glutamyl transpeptidase (gamma-GT), alanine aminotransferase, and aspartate aminotransferase (AST) in the prediction of diabetes and cardiovascular disease (CVD) in subjects free from hepatic diseases other than nonalcoholic fatty liver disease. The present analysis was performed on the cohort of subjects enrolled in the Firenze Bagno a Ripoli (FIBAR) study, a screening program for diabetes performed between 1 March 2001 and 31 December 2003 in the city of Florence on 3124 subjects who underwent an oral glucose tolerance test. Incident cases of diabetes in nondiabetic subjects (n = 2662) were obtained through databases of drug prescriptions, hospital admissions, and lists of subjects eligible for reimbursement. Incident CVD in subjects free of diabetes and CVD at enrollment (n = 2617) was identified through hospital admissions and through the register of causes of death. Mean follow-up was 39.6 +/- 12.0 months and 39.8 +/- 11.4 months for diabetes and CVD, respectively. Yearly incidence of diabetes and CVD was 0.4% and 0.2%, respectively. After adjustment for age and sex, gamma-GT >40 U/L was associated with increased incidence of diabetes and CVD (hazard ratio [95% confidence interval]: 2.54 [1.26-5.11], P < .05 and 2.21 [0.98-5.43], P < .10, respectively). Risk of diabetes, but not of CVD, was increased in patients with gamma-GT in the 25- to 40-U/L range. After adjustment for confounders, AST >40 U/L predicted CVD (hazard ratio, 6.5 [95% confidence interval, 1.5-28.1]), but not diabetes. Elevated gamma-GT or AST is an independent predictor of CVD. An increase of gamma-GT levels above the reference range, or also in the upper reference range, is an independent predictor of incident diabetes.

Role of endothelin-1 in the migration of human olfactory gonadotropin-releasing hormone-secreting neuroblasts.

FNC-B4 neuroblasts that express both neuronal and olfactory markers have been established and cloned. These cells express GnRH and both the endothelin-1 (ET-1) gene and protein and respond in a migratory manner to GnRH in a dose-dependent manner. Previous research has shown that FNC-B4 cells produce and respond to ET-1 by regulating the secretion of GnRH through endothelin type A receptors and by stimulating their proliferation through endothelin type B (ETB) receptors. In this study, we found that FNC-B4 cells are able to migrate in response to ET-1 through the involvement of ETB receptors. Combined immunohistochemical and biochemical analyses showed that ET-1 triggered actin cytoskeletal remodeling and a dose-dependent increase in migration (up to 6-fold). Whereas the ETB receptor antagonist (B-BQ788) blunted the ET-1-induced effects, the ETA receptor antagonist (A-BQ123) did not. Moreover, we observed that FNC-B4 cells were independently and selectively stimulated by ET-1 and GnRH. We suggest that ET-1, through ETB receptor activation, may be required to maintain an adequate proliferative stem cell pool in the developing olfactory epithelium and the subsequent commitment to GnRH neuronal migratory pattern. The coordinate interaction between ET receptors and GnRH receptor participates in the fully expressed GnRH-secreting neuron phenotype.

Lipid accumulation product and 25-OH-vitamin D deficiency in type 2 diabetes.

BACKGROUND: Emerging data suggest a link between vitamin D (25(OH)D) deficiency, type 2 diabetes (T2D), and visceral adiposity. The lipid accumulation product (LAP), strictly correlated with abdominal fat depots, is proposed as marker of dysfunctional adiposity. AIM: To verify the association between 25(OH)D levels and LAP in T2D. METHODS: Body mass index (BMI), waist circumference (WC), glucose, HbA1c, lipids, and 25(OH)D were assessed in 420 T2D outpatients and in 150 non-diabetic obese with similar anthropometric characteristics. LAP was computed as the product of sex-specific enlarged WC and triglycerides (TG). RESULTS: In T2D patients, 63.0% showed 25(OH)D deficiency (<20 ng/ml) vs. 71.3% in the obese control group. Overweight males showed a higher prevalence of 25(OH)D deficiency (60.3%) than women (48.8%, p < 0.001), while in obese patients this prevalence was not significant. In both genders, 25(OH)D was not significantly associated with HbA1c and fasting glucose. Age-adjusted 25(OH)D levels were inversely correlated with BMI (p < 0.001), WC (p < 0.001), and LAP (p < 0.001) in both genders. Metabolic syndrome presented an odds ratio (OR) for 25(OH)D deficiency of 1.6 (1.1-2.5, p = 0.048) in females and 1.7 (1.2-2.7, p = 0.016) in males, while the highest quartile of LAP showed an OR of 2.1 (1.2-3.6, p = 0.019) in females and 3.2 (1.6-6.5, p = 0.02) in males. A similar trend was observed in the obese control group. CONCLUSIONS: In the presence of excess weight, subjects with and without T2D frequently feature low 25(OH)D levels. Subjects with higher LAP exhibit a high risk of 25(OH)D deficiency, suggesting that dysfunctional adiposity is a worsening factor for vitamin D hypovitaminosis.

Dyslipidemia and diabetes: reciprocal impact of impaired lipid metabolism and Beta-cell dysfunction on micro- and macrovascular complications.

Patients with diabetes frequently exhibit the combined occurrence of hyperglycemia and dyslipidemia. Published data on their coexistence are often controversial. Some studies provide evidence for suboptimal lifestyle and exogenous hyperinsulinism at "mild insulin resistance" in adult diabetic patients as main pathogenic factors. In contrast, other studies confirm that visceral adiposity and insulin resistance are the basic features of dyslipidemia in type 2 diabetes (T2D). The consequence is an excess of free fatty acids, which causes hepatic gluconeogenesis to increase, metabolism in muscles to shift from glucose to lipid, beta-cell lipotoxicity, and an appearance of the classical "lipid triad", without real hypercholesterolemia. Recently, it has been proposed that cholesterol homeostasis is important for an adequate insulin secretory performance of beta-cells. The accumulation of cholesterol in beta-cells, caused by defective high-density lipoprotein (HDL) cholesterol with reduced cholesterol efflux, induces hyperglycemia, impaired insulin secretion, and beta-cell apoptosis. Data from animal models and humans, including humans with Tangier disease, who are characterized by very low HDL cholesterol levels, are frequently associated with hyperglycemia and T2D. Thus, there is a reciprocal influence of dyslipidemia on beta-cell function and inversely of beta-cell dysfunction on lipid metabolism and micro- and macrovascular complications. It remains to be clarified how these different but mutually influencing adverse effects act in together to define measures for a more effective prevention and treatment of micro- and macrovascular complications in diabetes patients. While the control of circulating low-density lipoprotein (LDL) cholesterol and the level of HDL cholesterol are determinant targets for the reduction of cardiovascular risk, based on recent data, these targets should also be considered for the prevention of beta-cell dysfunction and the development of type 2 diabetes. In this review, we analyze consolidated data and recent advances on the relationship between lipid metabolism and diabetes mellitus, with particular attention to the reciprocal effects of the two features of the disease and the development of vascular complications.

Effects of glucagon-like peptide-1 receptor agonists on body weight: a meta-analysis.

Glucagon-Like Peptide-1 receptor agonists (GLP-1RAs), approved as glucose-lowering drugs for the treatment of type 2 diabetes, have also been shown to reduce body weight. An extensive Medline, Cochrane database, and Embase search for "exenatide," "liraglutide," "albiglutide," "semaglutide," and "lixisenatide" was performed, collecting all randomized clinical trials on humans up to December 15, 2011, with a duration of at least 24 weeks, comparing GLP-1 receptor agonists with either placebo or active drugs. Twenty two (7,859 patients) and 7 (2,416 patients) trials with available results on body weight at 6 and 12 months, respectively, were included. When compared with placebo, GLP-1RAs determine a reduction of BMI at 6 months of -1.0 [-1.3; -0.6] kg/m(2). Considering the average BMI at baseline (32.4 kg/m(2)) these data means a weight reduction of about 3% at 6 months. This result could seem modest from a clinical standpoint; however, it could be affected by many factors contributing to an underestimation of the effect of GLP-1RA on body weight, such as non adequate doses, inclusion criteria, efficacy of GLP-1RA on reducing glycosuria, and association to non-pharmacological interventions not specifically aimed to weight reduction.

Sustained exendin-4 secretion through gene therapy targeting salivary glands in two different rodent models of obesity/type 2 diabetes.

Exendin-4 (Ex-4) is a Glucagon-like peptide 1 (GLP-1) receptor agonist approved for the treatment of Type 2 Diabetes (T2DM), which requires daily subcutaneous administration. In T2DM patients, GLP-1 administration is reported to reduce glycaemia and HbA1c in association with a modest, but significant weight loss. The aim of present study was to characterize the site-specific profile and metabolic effects of Ex-4 levels expressed from salivary glands (SG) in vivo, following adeno-associated virus-mediated (AAV) gene therapy in two different animal models of obesity prone to impaired glucose tolerance and T2DM, specifically, Zucker fa/fa rats and high fed diet (HFD) mice. Following percutaneous injection of AAV5 into the salivary glands, biologically active Ex-4 was detected in the blood of both animal models and expression persisted in salivary gland ductal cell until the end of the study. In treated mice, Ex-4 levels averaged 138.9±42.3 pmol/L on week 6 and in treated rats, mean circulating Ex-4 levels were 238.2±72 pmol/L on week 4 and continued to increase through week 8. Expression of Ex-4 resulted in a significant decreased weight gain in both mice and rats, significant improvement in glycemic control and/or insulin sensitivity as well as visceral adipose tissue adipokine profile. In conclusion, these results suggest that sustained site-specific expression of Ex-4 following AAV5-mediated gene therapy is feasible and may be useful in the treatment of obesity as well as trigger improved metabolic profile.

Failure to metformin and insulin secretagogue monotherapy: an observational cohort study.

The aim of the present cohort study is the assessment of treatment failure rates in patients on monotherapy with metformin or insulin secretagogues, observed in a routine clinical setting. A cohort of patients without any pharmacological treatment was also observed. A retrospective observational cohort study was performed on a consecutive series of 2,020 type 2 diabetic patients receiving monotherapy with an oral agent (metformin or insulin secretagogue, n = 1,126) or drug-naive (n = 894). HbA1c and prescribed hypoglycemic therapy were recorded yearly. Patients were followed until death, change of residence, failure to treatment, or up to 48 months. The mean duration of follow up was 34.8 ± 18.0 months. In a Cox regression analysis, metformin was associated with a significant reduction, and insulin secretagogues with a significant increase, in the risk of failure to therapy during follow up. When duration of diabetes and baseline BMI were added to the model, insulin secretagogues, but not metformin, were still associated with increased risk of failure. In conclusion, insulin secretagogues are associated with increased failure rate in comparison with metformin. This difference could be due to detrimental effect of secretagogues, rather than to a beneficial action of metformin.

Zonisamide Combined with Cognitive Behavioral Therapy in Binge Eating Disorder: A One-year Follow-up Study.

UNLABELLED: Objective. Binge eating disorder is a serious, prevalent eating disorder that is associated with overweight. Zonisamide is an antiepileptic drug that can promote weight loss. We evaluated the efficacy and safety of zonisamide as augmentation to individual cognitive behavioral therapy in the treatment of binge eating disorder patients. DESIGN: controlled open study. PARTICIPANTS: Twenty four threshold and subthreshold binge eating disorder patients were enrolled in the cognitive behavioral therapy treatment group, and 28 patients in the cognitive behavioral therapy plus zonisamide group. MEASUREMENTS: At the beginning (T0), at the end (T1) of treatment, and one year after the end of treatment (T2), body mass index was measured and Eating Disorder Examination-Questionnaire, Binge Eating Scale, Beck Depression Inventory, and State-Trait Anxiety Inventory were administered.Results. At T1 the cognitive behavioral therapy plus zonisamide group showed a higher mean reduction of body mass index, Eating Disorder Examination-Questionnaire, Beck Depression Inventory, and Binge Eating Scale scores. At T2, the cognitive behavior therapy group regained weight, while the cognitive behavioral therapy plus zonisamide group reduced their body mass and showed a higher reduction in binge eating frequency and Binge Eating Scale, Eating Disorder Examination-Questionnaire Restraint, and State and Trait Anxiety Inventory scores.Conclusion. The zonisamide augmentation to individual cognitive behavior therapy can improve the treatment of binge eating disorder patients, reducing body weight and the number of binge eating episodes. These results are maintained one year after the end of treatment.

Metformin beyond diabetes: new life for an old drug.

Metformin is a widely used drug in the therapy of patients affected by diabetes mellitus. Although some caution is needed in the very old, advanced age per se does not represent a contraindication to metformin use. Despite the fact that its precise mechanism of action it is not completely elucidated, long-term treatment with this drug in monotherapy, improves glycaemic control and reduces cardiovascular mortality in overweight type 2 diabetic patients. Experimental evidence produced over the years suggests that metformin may be useful in some clinical conditions different from diabetes mellitus. In the present review we have examined currently available data about the possible use of metformin as an effective therapeutical agent in pathological conditions different from type 2 diabetes mellitus. On the basis of our investigation, the use of metformin can be suggested in overweigth patients affected by impaired glucose tolerance and/or fasting hyperglycaemia and in subjects affected by polycystic ovary syndrome, while further data are needed in order to prescribe such a drug in patients affected by non-alcoholic steato-hepatitis and in HIV patients on antiretroviral therapy.

Dipeptidyl peptidase-IV expression and activity in human glomerular endothelial cells.

Glucagon-like peptide-1 (GLP-1), a meal-stimulated gastrointestinal insulinotropic hormone inactivated by dipeptidyl peptidase-IV (DPP-IV), is reduced in type 2 diabetic patients. The present study shows that 2-week exposure of human glomerular endothelial cells to high glucose (22 mM) determines a highly significant increase in DPP-IV activity and mRNA expression, which cannot be entirely accounted for by hyperosmolarity. On the other hand, incubation of purified DPP-IV in a buffer solution added with high glucose does not affect enzyme activity. These results suggest that high glucose increases expression and activity of DPP-IV, possibly contributing to GLP-1 reduction in type 2 diabetic patients.

AT1 and AT2 receptors in human glomerular endothelial cells at different passages.

In human adult kidney angiotensin II (AngII) effects are mediated by the AT1 receptor, while the functions of AT2 receptors are mostly unknown. Since AngII regulates endothelial cell growth by AT1 and AT2 receptors, we analysed their functional aspects at different passages in human glomerular endothelial cells (GENC). Semiquantitative reverse transcription-polymerase chain reaction revealed the presence of AT1 and AT2 receptors between 2p and 15p cell passages with different levels of expression. In fact, binding studies of different families of displacement curves using AngII, DUP753 (AT1 antagonist), and PD123177 (AT2 antagonist) showed the presence of AT1a and AT2 receptors at 4p-9p while in GENC 2p only the presence of AT2. In terms of mitogenic activity, AngII was unable to stimulate GENC 2p growth. On the contrary, in GENC 4p-9p and 15p a significant thymidine incorporation was observed. This stimulatory effect seemed to be induced also by the concomitant release of PDGF-BB AT1a mediated. In conclusion, AT1a and AT2 receptors are represented in GENC with a different ratio depending upon the cell passage. AngII regulates the mitogenic effect through AT1a receptors (in later cell passages 4p-15p) involving the release of PDGF-BB, while AT2 (in early cell passage 2p) showed a predominant negative growth control.