Biomedical subjects

Giuseppe Paolisso

Publications and source records attributed to Giuseppe Paolisso.

48 records · Page 3Linked to original sources

PubMed2002

Effect of tibolone administration on heart rate variability and free fatty acid levels in postmenopausal women.

OBJECTIVE: To evaluate the effects of tibolone on heart rate variability and plasma free fatty acid levels in postmenopausal women. DESIGN: Randomized, placebo-controlled trial. SETTING: University hospital. PATIENT(S): Thirty postmenopausal women. INTERVENTION(S): Tibolone, 2.5 mg/d, or placebo for 4 months. MAIN OUTCOME MEASURES: Variability in heart rate and changes in the lipid profile. RESULT(S): Anthropometric data were unchanged throughout the study. Compared with placebo, long-term tibolone administration was associated with a decrease in plasma levels of low-density lipoprotein cholesterol, triglyceride, and free fatty acid and homeostasis model assessment index. Furthermore, tibolone administration was associated with an increase in RR interval, total power, and high frequency and decrease in low frequency and the low frequency/high frequency ratio. Finally, the delta decrease in plasma free fatty acid levels correlated with delta low frequency/high frequency ratio independently of age, delta body mass index, delta homeostasis model assessment index, and low-density lipoprotein cholesterol levels. CONCLUSION(S): Long-term tibolone administration improves the ratio of cardiac sympathetic tone to parasympathetic tone in postmenopausal women.

Cholesterol, LDL↗

PubMed2002

Elevated plasma activator inhibitor 1 is not related to insulin resistance and to gene polymorphism in healthy centenarians.

Previous studies demonstrated a relationship between the degree of insulin resistance and plasma plasminogen activator inhibitor type-1 (PAI-1) levels. We aim at investigating the relationship between the degree of insulin resistance and plasma PAI-1 levels in aged subjects (n=83) and in healthy centenarians (n=42). In all subjects the degree of insulin resistance was assessed by HOMA method. Our data demonstrated that healthy centenarians have higher plasma PAI-1 levels (73.1+/-13.9 vs 23.7+/-14.7 ng/ml, P<0.001) and lower degree of insulin resistance (1.4+/-0.5 vs 3.3+/-1.3, P<0.001) than aged subjects. In aged subjects plasma PAI-1 levels correlated with the degree of insulin resistance (r=0.61, P<0.001), fasting plasma triglycerides (r=0.74, P<0.001) and age (r=0.33, P<0.001). All such associations were lost in centenarians. Plasma PAI-1 Ag levels were also similar in aged subjects and centenarians even after categorization for PAI gene polymorphism. In multivariate analysis, a model made by age, sex, body mass index, fasting plasma triglycerides, HOMA and PAI-1 gene explained 65 and 50% of plasma PAI-1 level variations in aged subjects and centenarians, respectively. Nevertheless, HOMA (P<0.001) was significantly and independently associated with plasma PAI-1 levels only in aged subjects. In conclusion, our data demonstrates that in healthy centenarians, plasma PAI-1 were not associated with the degree of insulin resistance as in aged subjects. Frequency of PAI-1 genotype does not provide an explanation for such differences between aged subjects and centenarians.

Adult↗

PubMed2002

Leptin affects adenylate cyclase activity in H9c2 cardiac cell line: effects of short- and long-term exposure.

Leptin has been hypothesized to be a pathophysiologic link between obesity and cardiovascular diseases. Because the adenylate cyclase (AC) system is a main effector of beta-adrenergic receptors and leptin has been shown to modulate AC activity in other cell lines, a leptin impact on cardiac AC activity was hypothesized. Therefore, acute and chronic effects of leptin on a rat cardiac cell line (H9c2) were investigated. Leptin affected both basal (+ 13% at 30 min and -16.4% after 18 h v untreated cells) and catecholamine-stimulated AC activity (isoproterenol + leptin at 30 min or 18 h was +21% v untreated cells; norepinephrine + leptin at 30 min was +38.8% v untreated cells; and norepinephrine + leptin at 18 h was +6% v untreated cells). Thus, long-term leptin treatment was associated with a reduced AC activity and a different responsiveness to catecholamines. The AC activity on leptin treatment was accompanied by changes in levels of proteins structurally or functionally related to AC complex (AC, Gas, Gai, p21-ras). These data indicate that the AC complex is profoundly affected at more than one level by leptin treatment in the H9c2 cardiac cell line. Differences in AC activity after short- and long-term exposure to leptin and the interaction between leptin and catecholamine might provide further insight to the understanding of the development of hypertension and congestive heart failure in obese patients.

Adenylyl Cyclases↗

PubMed2002

Positive association between circulating free insulin-like growth factor-1 levels and coronary flow reserve in arterial systemic hypertension.

BACKGROUND: The reduction of coronary flow reserve (CFR) found in arterial hypertension may be due to changes in afterload, left ventricular (LV) structure, and metabolic factors. Also, insulin-like growth factor-1 (IGF-1) may be associated with the magnitude of CFR in relation to its modulating action on cardiac and endothelial function. METHODS: A total of 44 newly diagnosed, untreated hypertensive patients, who were free of diabetes mellitus and coronary artery disease, underwent M-mode analysis, second-harmonic Doppler echocardiographic assessment of CFR (dipyridamole infusion 0.56 mg/kg intravenously in four patients), determination of circulating free IGF-1, and insulin resistance. Based on CFR levels, hypertensive subjects were divided into two groups: 18 with normal CFR (> or = 2) and 26 with impaired CFR (<2). RESULTS: Patients with normal CFR had lower diastolic blood pressure, heart rate, and LV mass index but higher free circulating IGF-I than patients with reduced CFR (P < .001). Insulin resistance was not significantly different between the two groups. In a first multilinear regression analysis that included demographic and echocardiographic variables, insulin resistance was independently associated with CFR (standardized beta coefficient = -0.31, P < .05) in the overall population. However, in a subsequent model which included also IGF-1, the relationship between insulin resistance and CFR disappeared, whereas IGF-1 was the main independent determinant of CFR (beta = 0.51, P < .0002). CONCLUSIONS: Free IGF-1 circulating levels are independently associated with CFR in hypertensive individuals free of overt coronary artery disease. A possible beneficial effect exerted by IGF-1 on coronary blood flow may be supposed in arterial hypertension.

Adult↗

PubMed2002

Genetic analysis of Paraoxonase (PON1) locus reveals an increased frequency of Arg192 allele in centenarians.

Human Paraoxonase (PON1) is a High-Density Lipoprotein (HDL)-associated esterase that hydrolyses lipo-peroxides. PON1 has recently attracted attention as a protective factor against oxidative modification of LDL and may therefore play an important role in the prevention of the atherosclerotic process. Two polymorphisms have been extensively studied: a Leucine (L allele) to Methionine (M allele) substitution at codon 55, and a Glutamine (A allele) to Arginine (B allele) substitution at codon 192. We have examined these two aminoacidic changes in 579 people aged 20 to 65 years old, and 308 centenarians. We found that the percentage of carriers of the B allele at codon 192 (B+ individuals) is higher in centenarians than in controls (0.539 vs 0.447), moreover we found that among the B+ individuals, the phenomenon was due to an increase of people carrying M alleles at codon 55 locus. In conclusion, we propose that genetic variability at PON1 locus affects survival at extreme advanced age.

Adult↗

PubMed2002

Relationship between autonomic cardiac activity, beta-cell function, anthropometrics and metabolic indices in type II diabetics.

OBJECTIVE: Recent studies have demonstrated that C-peptide exerts beneficial effects on the diabetic state, including improvements in kidney and nerve function. Thus, we investigated the effect of residual pancreatic C-peptide secretion on the cardiac autonomic nervous system in well- and poorly controlled type II diabetic patients. DESIGN: Randomised cross-sectional study. PATIENTS: Forty type II diabetic patients free from diabetic neuropathy, with similar anthropometric parameters, volunteered for our study. MEASUREMENTS: Insulin action, residual pancreatic C-peptide secretion and the cardiac autonomic nervous system were investigated by euglycaemic hyperinsulinaemic clamp, glucagon bolus test and heart rate variability, respectively. M-values were used as an index of insulin sensitivity. High frequency (HF) and low frequency (LF) oscillations in heart rate were analysed. RESULTS: The patients were categorized into those with good (HbA1c < or = 7.0) and poor (HbA1c > or = 8.0) metabolic control. The patients with good metabolic control had fasting plasma glucose and C-peptide levels, plasma area under the curve (auc) insulin and C-peptide levels, M-values, LF values and LF/HF ratio significantly lower than patients with poor metabolic control. In contrast, RR interval, total power and HF values had an opposite trend. Basal plasma C-peptide correlated with LF/HF in patients with good (r = -0.42; P < 0.05) and poor metabolic control (r = -0.45; P < 0.05). An even stronger correlation between auc C-peptide and LF/HF in patients with good (r = -0.53, P < 0.002) and poor metabolic control (r = -0.49; P < 0.03), as well as in the whole group (r = -0.83; P < 0.001) was found. By multiple regression analyses performed in all patients, LF/HF were independently associated with auc C-peptide (t = -8.618; P < 0.001) but not basal C-peptide levels (t = -0.137; P < 0.88). CONCLUSION: Our study demonstrated that preserved C-peptide secretion is associated with a well balanced cardiac autonomic activity in type II diabetic patients.

Area Under Curve↗

PubMed2002

LL-paraoxonase genotype is associated with a more severe degree of homeostasis model assessment IR in healthy subjects.

The LL genotype among subjects with paraoxonase (PON) polymorphism Met-Leu 54 has been shown to be associated with elevated risk of coronary heart disease. Indeed, insulin resistance (IR) is a well known cardiovascular risk factor that is likely attributable to a genetic background, lifestyle, and environmental factors such oxidative stress. Because subjects sharing the LL genotype have a more elevated degree of oxidative stress, one cannot rule out that in those subjects a more severe degree of IR can occur. Thus, the possible relationship between PON gene polymorphism and degree of IR was investigated. In 213 healthy subjects, the degree of IR was assessed by the homeostasis model assessment, and the Met-Leu 54 PON polymorphism was detected. The frequency was 0.366 for the LL genotype, 0.469 for the LM genotype, and 0.164 for the MM genotype. Comparing the three genotype groups, LL genotype had the more severe degree of IR, compared with LM (P < 0.01) and MM (P < 0.01) genotypes. No difference between LM and MM genotypes was found (P = 0.49). Subjects carrying the LL genotype were associated with the IR syndrome picture more than individuals carrying the M allele because they were more overweight and had the highest levels of triglycerides and blood pressure and the lowest values of plasma high-density lipoprotein cholesterol. In a multivariate stepwise regression analysis, LL genotype was a significant predictor of IR, independent of age, sex, body mass index, fasting plasma triglycerides, and high-density lipoprotein cholesterol (P < 0.001). In conclusion, the presence of LL PON genotype is associated with a more severe degree of IR. Thus, IR might be the possible missing link between Met-Leu 54 PON polymorphism and the increased cardiovascular risk.

Aryldialkylphosphatase↗

PubMed2002

FFAs and QT intervals in obese women with visceral adiposity: effects of sustained weight loss over 1 year.

We evaluated 66 obese patients grouped by waist-to-hip ratio (WHR) into group A (WHR > 0.85, n = 30) and group B (WHR < or = 0.85, n = 36), before and after 1 yr of diet-induced weight loss compared with 25 nonobese women. Before diet, the longest values of QT intervals and the highest levels of FFA and catecholamines were in group A (P < 0.01). In obese women (both groups), the corrected QT (QTc); interval correlated with plasma FFA (P < 0.01) and catecholamine (P < 0.02) concentrations. After 1 yr of diet, at the same levels of body weight reduction, the decrement of the QTc interval (P < 0.02), FFA (P < 0.01) and catecholamine (P < 0.02) levels were significantly greater in-group A than group B. In multivariate analysis, the decline of the QTc interval after weight loss was associated with changes in plasma FFA independently of changes in WHR and plasma catecholamines. Our data suggest that the QTc interval is tightly correlated with plasma FFA levels; shortening of cardiac repolarization times in the course of long-lasting weight reduction may reduce the risk of ventricular electrical instability, especially in women with abdominal adiposity.

Adipose Tissue↗

PubMedDate not supplied

Changing the metabolic profile by large-volume liposuction: a clinical study conducted with 123 obese women.

Adipose tissue is a metabolically active tissue. The hypertrophic fat cells of obese patients produce increased quantities of leptin and tumor necrosis factor-alpha (TNF-alpha) and are less sensitive to insulin. This study aimed to determine whether aspirating large amounts of these subcutaneous fat cells by large-volume liposuction (LVL), could change the metabolic profile in 123 obese women. All the patients had a main central body fat distribution (waist-hip ratio, 0.91+/-0.01) and a body mass index of 32.8 +/- 0.8 kg/m). They were studied for 90 days after LVL to determine their changes in insulin sensitivity, resting metabolic rate, serum adipocytokines, and inflammatory marker levels. During 3 months of follow-up evaluation, LVL resulted in a significantly improved insulin sensitivity, resting metabolic rate, serum adipocytokines, and inflammatory marker levels. Such parameters correlate with a decrease in fat mass and waist-hip ratio. Interestingly, no significant changes were seen between the first (21 days) and second (90 days) metabolic determinations after LVL. However, these findings, confirm other preliminary data published previously, and could change the actual role of LVL in the multidisciplinary treatment of obesity.

Adipocytes↗

PubMedDate not supplied

Role of magnesium in insulin action, diabetes and cardio-metabolic syndrome X.

Magnesium (Mg) is one of the most abundant ions present in living cells and its plasma concentration is remarkably constant in healthy subjects. Plasma and intracellular Mg concentrations are tightly regulated by several factors. Among them, insulin seems to be one of the most important. In vitro and in vivo studies have demonstrated that insulin may modulate the shift of Mg from extracellular to intracellular space. Intracellular Mg concentration has also been shown to be effective in modulating insulin action (mainly oxidative glucose metabolism), offset calcium-related excitation-contraction coupling, and decrease smooth cell responsiveness to depolarizing stimuli. A poor intracellular Mg concentration, as found in noninsulin-dependent diabetes mellitus (NIDDM) and in hypertensive patients, may result in a defective tyrosine-kinase activity at the insulin receptor level and exaggerated intracellular calcium concentration. Both events are responsible for the impairment in insulin action and a worsening of insulin resistance in noninsulin-dependent diabetic and hypertensive patients. By contrast, in NIDDM patients daily Mg administration, restoring a more appropriate intracellular Mg concentration, contributes to improve insulin-mediated glucose uptake. The benefits deriving- from daily Mg supplementation in NIDDM patients are further supported by epidemiological studies showing that high daily Mg intake are predictive of a lower incidence of NIDDM. In conclusion, a growing body of studies suggest that intracellular Mg may play a key role in modulating insulin-mediated glucose uptake and vascular tone. We further suggest that a reduced intracellular Mg concentration might be the missing link helping to explain the epidemiological association between NIDDM and hypertension.

Diabetes Mellitus, Type 2↗

PubMedDate not supplied

Glucose regulation and oxidative stress in healthy centenarians.

Aging, oxidative stress and insulin resistance are strongly correlated. There is a growing body of evidence showing that aging is associated with a significant rise in oxidative stress mainly due to a decline in anti-oxidant activity and a rise in pro-oxidant factors such as glucose and insulin concentrations. Furthermore, aging is also associated with a progressive rise in insulin resistance which is due to a complex network of environmental, anthropometric and neuro-hormonal factors. It is noteworthy that extreme longevity, e.g. centenarians, is associated with a low degree of oxidative stress and insulin resistance. The causes for such differences between aged subjects and centenarians is not fully understood. It is likely that a specific genetic background might play a role. However, the insulin gene does not seem to be involved for explaining such age-related differences.

Aged↗

PubMedDate not supplied

Effects of soy isoflavones on endothelial function in healthy postmenopausal women.

OBJECTIVE: To evaluate the effects of soy isoflavone administration on endothelial function in healthy postmenopausal women. DESIGN: Sixty naturally postmenopausal women were randomly assigned to receive isoflavone or placebo tablets for 6 months. Endothelium-dependent vasodilatation was measured by brachial reactivity technique along with levels of plasma soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin and soluble thrombomodulin, von Willebrand factor, and tissue plasminogen activator. Differences between endothelium-dependent and endothelium-independent vasodilatation were assessed by evaluating brachial reactivity parameters after reactive hyperemia and after sublingual administration of nitroglycerin; furthermore, in the active group, the effect of isoflavones was also evaluated during the intra-arterial infusion of N-monomethyl-L-arginine. Serum levels of lipids [high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides and lipoprotein(a)] and hemostatic factors (prothrombin, fibrinogen, plasminogen activator inhibitor-1, and fibrin D-dimer) were also measured. To confirm the absorption of isoflavones, their blood concentrations were determined. RESULTS: Isoflavone treatment versus placebo was associated with a significant improvement in endothelium-dependent vasodilatation but had no impact on endothelial-independent arterial diameter and flow. Intra-arterial infusion of N-monomethyl-L-arginine inhibited the significant effect of isoflavones on endothelium-mediated vasodilatation. Furthermore, isoflavone group experienced statistically significant reductions in plasma concentrations of ICAM-1, VCAM-1, and E-selectin. Levels of soluble thrombomodulin, von Willebrand factor, tissue plasminogen activator, lipids, and hemostatic factors did not change significantly throughout the study in both groups. CONCLUSIONS: Our findings suggest a positive influence of soy isoflavones on endothelial function in healthy postmenopausal women as evidenced by an improvement in endothelium-dependent vasodilatation and a reduction in plasma adhesion molecule levels.

Brachial Artery↗