RESUMO
AIM: In the last years there has been a progressive reduction of the average duration of sleep and an increase in the incidence of sleep disturbances. At the same time, an increase of the incidence of the metabolic syndrome has been described, partly attributable to the progressive worsening of dietary habits and the increase in sedentary lifestyle. Recent studies suggest that adequate sleep is essential to maintain good glucose metabolism and sleep disturbances may contribute to the manifestation of the metabolic syndrome. Benzodiazepines (BZ), such as brotizolam, and imidazopyridines, such as zolpidem, are frequently used as hypnotics but their potential impact on glucose metabolism has never been evaluated so far. METHODS: In 12 healthy volunteers [age (mean ± SEM) 38.3 ± 8.1 years; body mass index (BMI) 21.9 ± 0.8 kg/m²] we studied glucose and insulin responses to oral glucose tolerance test (OGTT, 75 g) before and after 15 days treatment with brotizolam 0.25 mg/day or zolpidem 10 mg/day. RESULTS: Brotizolam increased glucose delta area under curve response to the OGTT by 122 % (p < 0.01) and zolpidem by 86 % (p < 0.01) without significant variations of insulin levels, suggesting an impact on insulin sensitivity and/or insulin secretion. CONCLUSIONS: This study suggests that BZ and imidazopyridines have a rapid glucometabolic effect that is detectable as early as after 15 days treatment.
Assuntos
Benzodiazepinas/administração & dosagem , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Piridinas/administração & dosagem , Adulto , Azepinas/administração & dosagem , Azepinas/efeitos adversos , Benzodiazepinas/efeitos adversos , Metabolismo dos Carboidratos/efeitos dos fármacos , Esquema de Medicação , Feminino , Teste de Tolerância a Glucose , Saúde , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Piridinas/efeitos adversos , Fatores de Tempo , ZolpidemRESUMO
BACKGROUND: It is well recognized that beta-adrenergic receptors mediate important endocrine and metabolic actions. In fact, beta-adrenergic receptor activation negatively influences GH secretion while exerting relevant metabolic actions such as the stimulation of insulin secretion, glycogenolysis, and lipolysis. AIM: We have already shown that the activation of the GH secretagogue receptor (GHS-R)-1a by acylated ghrelin (AG) counteracts the inhibitory effect of salbutamol (SALB), a beta2-adrenergic agonist, on GH release. The aim of the present study in humans was to clarify whether the metabolic response to SALB is affected by the infusion of AG, also known to exert significant metabolic actions. METHODS: Six healthy young male volunteers underwent the following testing sessions in random order at least 5 days apart: a) SALB (0.06 microg/kg/min iv from 0 to 60 min) alone; b) SALB in combination with AG (1.0 microg/kg/min iv from -60 to 60 min); c) isotonic saline. Insulin, glucose, and free fatty acids (FFA) levels were evaluated every 15 min. RESULTS: As expected, with respect to saline, SALB administration tended to increase both insulin secretion [Delta area under the curve (DeltaAUC): 0.16+/-0.09 vs 0.003+/-0.077 x 10(3) microU/ml/min; p>0.05] and FFA levels (DeltaAUC: 8.0+/-7.3 vs -4.0+/-4.0 mEq/l/min; p>0.05), while glucose levels did not change. The metabolic response to SALB was significantly modified under the exposure of AG. In fact, under AG infusion, SALB elicited a more marked increase of FFA (DeltaAUC: 22.3+/-3.2 vs 8.0+/-7.3 mEq/l/min; p<0.05) as well as a slight elevation in insulin (DeltaAUC: 0.37+/-0.11 vs 0.16+/-0.09 x 10(3) microU/ml/min; p>0.05). Under AG, the baseline glucose levels were more elevated but, again, in combination with AG, SALB did not significantly modify glucose levels. CONCLUSIONS: Beta-adrenergic receptors and AG are likely to interact at the metabolic level. In humans, the lypolitic response to a beta2-adrenergic agonist such as SALB is amplified by AG. Meanwhile, during the co-treatment, the marginal insulinotropic effect was not associated with an increase in glycemia.
Assuntos
Albuterol/farmacologia , Grelina/metabolismo , Grelina/farmacologia , Receptores Adrenérgicos beta/efeitos dos fármacos , Acilação , Adulto , Glicemia/metabolismo , Ácidos Graxos não Esterificados/sangue , Hormônio do Crescimento Humano/metabolismo , Humanos , Insulina/metabolismo , Secreção de Insulina , Lipólise/efeitos dos fármacos , MasculinoRESUMO
BACKGROUND: Obestatin has been discovered as a new product of the ghrelin gene. Its physiological actions are still a matter of debate, but it seems that this peptide is likely to be involved in the control of insulin secretion and action as well as of adipocyte function. It has been already shown that obestatin secretion in humans is negatively modulated by food intake. AIM: To clarify obestatin secretion in normal subjects and in patients with Type 2 diabetes (T2D) in basal conditions and after a standardized meal. SUBJECTS/METHODS: Five normal subjects and 5 T2D patients were studied during infusion of saline (iv for over 5 h from -120 to +180 min). A standardized lunch was served at 0 min. Obestatin, glucose, and insulin levels were assayed at -120, -90, -60, -45, -30, -15, 0, 15, 30, 45, 60, 90, 120, 150, and 180 min. RESULTS: From -120 to 0 min, obestatin levels in normal and T2D subjects were similar (area under the curve: 32.3+/-5.6 pg/ml/min vs 31.1+/-1.0 pg/ml/min). After the meal, circulating obestatin levels underwent a clear decrease in normal subjects (0 min: 300.6+/-34.7 pg/ml vs nadir at 60 min: 161.8+/-29.4 pg/ml; p=0.002) but not in diabetic patients (0 min: 267.2+/-16.5 pg/ml vs nadir at 180 min: 226.0+/-10.5 pg/ml). CONCLUSION: This study shows that normal and diabetic subjects display similar levels of circulating obestatin in fasting condition. However patients with T2D look refractory to the inhibitory effect of meal on obestatin secretion.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Grelina/sangue , Idoso , Glicemia/metabolismo , Ingestão de Alimentos , Jejum , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Acylated ghrelin (AG) is a physiological GH secretion amplifier, in part stimulating GHRH neurones and antagonizing somatostatin activity. In humans, AG is one of the most potent pharmacological stimuli of GH secretion and, unlike GHRH, is refractory to the inhibitory effect of glucose, free fatty acids (FFA) and somatostatin. Somatotroph secretion is also profoundly modulated by the adrenergic system. Indeed, beta-adrenergic agonists abolish spontaneous and GHRH-stimulated GH secretion. Based on these data, the aim of the present study was to investigate the effects of beta adrenergic agonism on the GH response to AG. SUBJECTS AND MEASUREMENTS: Six young healthy male volunteers underwent: (a) acute AG intravenous (iv) administration (1.0 microg/kg); (b) salbutamol infusion (SLB; 0.06 microg/kg/min iv); (c) AG + SLB; and (d) saline infusion. In all sessions GH levels were assayed every 15 min from time -30 to +210 min. RESULTS: SLB induced a significant (P < 0.05) inhibition of spontaneous GH secretion that persisted up to 75 min after SLB withdrawal. AG induced a marked increase (P < 0.01) in GH that was not modified by SLB. CONCLUSIONS: The GH-releasing effect of AG is refractory to the inhibitory effect of SLB-induced beta-adrenergic receptor activation. Although further studies are needed to confirm these results during the lifespan and particularly during prolonged exposure to beta agonists, the present data clearly suggest that, among GH stimulatory tests, AG administration might be the most suitable in clinical conditions of chronic treatment with beta-2 agonists, such as in asthmatic disease.
Assuntos
Agonistas Adrenérgicos beta/administração & dosagem , Albuterol/administração & dosagem , Grelina/metabolismo , Hormônio do Crescimento Humano/metabolismo , Somatostatina/administração & dosagem , Acilação , Adulto , Grelina/administração & dosagem , Hormônio do Crescimento Humano/sangue , Humanos , Infusões Intravenosas , MasculinoRESUMO
The aim of this study is to describe a potential modulatory effect of acute acylated ghrelin (AG) administration on the glucose, insulin, and free fatty acids (FFA) responses to salbutamol (SALBU). Six healthy young male volunteers underwent the following four testing sessions in random order at least 7 days apart: (a) acute AG administration (1.0 µg/kg i.v. as bolus at 0'); (b) SALBU infusion (0.06 µg/kg/min i.v. from -15' to +45'); (c) SALBU infusion+AG; and (d) isotonic saline infusion. Blood samples for glucose, insulin, and FFA levels were collected every 15 min. As expected, with respect to saline, SALBU infusion induced a remarkable increase in glucose (10.8±5.6 mmol/l×min; P<0.05), insulin (2436.8±556.9 pmol/l×min; P<0.05), and FFA (18.9±4.5 mmol/l×min; P<0.01) levels. A significant increase in glucose (7.4±3.9 mmol/l×min; P<0.05) and FFA levels (10.0±2.8 mmol/l×min; P<0.01) without significant variations in insulin levels were recorded after AG administration. Interestingly, the hyperglycemic effect of AG appeared to be significantly potentiated during SALBU infusion (26.7±4.8 mmol/l×min; P<0.05). On the other hand, the stimulatory effect of SALBU on insulin and FFA was not significantly modified by AG administration. The results of this study show that acute AG administration has a synergic effect with ß2-adrenergic receptor activation by SALBU on blood glucose increase, suggesting that their pharmacological hyperglycemic action takes place via different mechanisms. On the other hand, AG has a negligible influence on the other pharmacological metabolic effects of SALBU infusion.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Albuterol/farmacologia , Glicemia/metabolismo , Ácidos Graxos não Esterificados/sangue , Grelina/farmacologia , Insulina/sangue , Adulto , Humanos , MasculinoRESUMO
At the National Committee for Research and Development of Nuclear Energy and Alternate Energy Sources (ENEA) Center of Frascati, there are several radiation-producing machines: two tokamaks and three electron accelerators; moreover, a neutron generator will begin to operate in a short time. A completely automatic monitoring system has been developed. Radiation control is performed by means of classical active and passive detectors. An automatic acquisition system has been developed: Measured quantities are acquired and stored in a specific data base; information regarding radioactivity levels, machines status, personnel dosimetry and meteorological parameters are available in real time. If any of the radiometric quantities exceeds appropriate reference levels, the following operations automatically activate: An automatic switch turns off the machines and an alarm signal is broadcast to the Health Physics group. In addition, the "Nuclear Emergency" software module starts if a radionuclide emission is detected. This module has been implemented to provide response to radiological emergencies in the ENEA nuclear research centers. The modularity of the computer-based system allows its utilization also in other nuclear centers, such as at nuclear power plants. When activated, the "Nuclear Emergency" displays an alarm signal and informs the Health Physics group about the monitor's location and characteristics and the measured data exceeding the reference level. If emission of radionuclides occurs, a preliminary evaluation of their diffusion in the atmosphere and an estimation of the population dose are performed. Statistical analysis of the event is also possible.
Assuntos
Sistemas Computacionais , Energia Nuclear , Monitoramento de Radiação , Emergências , Itália , Doses de RadiaçãoRESUMO
OBJECTIVE: GH secretion is regulated by an interplay between GH-releasing hormone (GHRH), somatostatin (SST), and other central and peripheral signals. Acylated ghrelin (AG) amplifies GH pulsatility acting, at least partially, independently from GHRH and SST. The GH response to GHRH is inhibited by recombinant human GH (rhGH), likely due to a SST-mediated negative GH auto-feedback. The effect of exogenous rhGH on the GH-releasing effect of AG has never been tested. DESIGN AND METHODS: In six healthy volunteers, we studied the GH response to acute AG administration (1.0 µg/kg i.v.) during saline or rhGH infusion (4.0 µg/kg per h i.v.) or after 4-day rhGH (10.0 µg/kg s.c.) administration. RESULTS: Compared with saline, rhGH infusion increased GH levels (P<0.01). During saline, acute i.v. AG induced a marked increase (P<0.01) in GH levels similar to those observed after AG administration during rhGH infusion. During s.c. rhGH, IGF1 levels rose from day 0 to day 5 (P<0.01). After 4-day s.c. rhGH, i.v. AG increased (P<0.01) GH levels, though significantly (P<0.05) less than on day 0. CONCLUSIONS: The marked somatotroph-releasing effect of AG is refractory to a direct GH auto-feedback whereas is markedly inhibited after 4-day rhGH administration, suggesting the possibility of a selective IGF1-mediated inhibitory feedback.