RESUMO
OBJECTIVE: Shift work is associated with circadian rhythm disorder, impaired sleep and behavioural changes, including eating habits, predisposing to obesity and metabolic dysfunctions. It involves a neuro-hormonal dysregulation of appetite towards positive energy balance, including increased ghrelin and decreased leptin, but little is known about other hormones, such as xenin, derived from the upper gut (like ghrelin), and lower gut hormones. Our objective was to compare night workers with day workers in relation to appetite-regulating hormones and other metabolic parameters. DESIGN: Cross-sectional, observational study. PARTICIPANTS: Twenty-four overweight women, divided into night shift workers (n = 12) and day shift workers (n = 12). MEASUREMENTS: BMI, waist circumference, fat mass percentage; diet composition; Pittsburgh Sleep Quality Index; lipids; adipokines; meal tolerance test curves of glucose, insulin, ghrelin, PYY3-36, oxyntomodulin, xenin, GLP-1; insulin sensitivity (Stumvoll index). RESULTS: Night workers, as compared with day workers, had greater body fat mass percentage and tendency to greater waist circumference despite similar BMI; greater energy intake; impaired sleep; lower insulin sensitivity; increased triglycerides and tendency to increased C-reactive protein; similar levels of leptin and other adipokines. Night workers had a blunted post-meal suppression of ghrelin (AUCi(0-60 min) 19·4 ± 139·9 vs -141·9 ± 9·0 ng/ml·60 min, P < 0·01); blunted rise of xenin (AUC(0-180 min) 8690·9 ± 2988·2 vs 28 504·4 ± 20 308·3 pg/ml·180 min, P < 0·01) and similar curves of PYY3-36, oxyntomodulin and GPL-1. CONCLUSION: Compared with day workers within the same BMI range, night workers presented a disrupted control of ghrelin and xenin, associated with behavioural changes in diet and sleep and increased adiposity and related metabolic alterations.
Assuntos
Regulação do Apetite/fisiologia , Hormônios Gastrointestinais/fisiologia , Grelina/fisiologia , Neurotensina/fisiologia , Tolerância ao Trabalho Programado/fisiologia , Adiposidade/fisiologia , Adulto , Estudos Transversais , Sistema Digestório/fisiopatologia , Ingestão de Energia/fisiologia , Feminino , Hormônios Gastrointestinais/sangue , Grelina/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Resistência à Insulina/fisiologia , Neurotensina/sangue , Sobrepeso/sangue , Sobrepeso/patologia , Sobrepeso/fisiopatologia , Oxintomodulina/sangue , Fragmentos de Peptídeos/sangue , Peptídeo YY/sangue , Transtornos do Sono do Ritmo Circadiano/sangue , Transtornos do Sono do Ritmo Circadiano/patologia , Transtornos do Sono do Ritmo Circadiano/fisiopatologiaRESUMO
CONTEXT: Recent studies have shown that xenin can act in the hypothalamus, reducing food intake through a leptin- and melanocortin system-independent mechanism. OBJECTIVE: To evaluate the impact of body mass reduction on the blood and cerebrospinal fluid (CSF) levels of xenin. DESIGN AND SETTING: Thirteen obese patients (11 women) selected for roux-in-Y gastric bypass surgery were evaluated before and approximately 8 months after surgery. Xenin was determined in serum and CSF by radioimmunoassay. RESULTS: As compared with lean subjects, obese patients have increased blood levels of xenin, which reduce after surgery. There are significant correlations between blood xenin and blood leptin and insulin levels. CSF concentration of xenin is â¼10-fold lower than blood levels, and is significantly higher in obese subjects as compared with lean ones, returning to normal levels after body mass reduction. There is a significant linear correlation between CSF and blood levels of xenin. CONCLUSION: Xenin is present in the human CSF in a concentration â¼10-fold lower than the blood. Both blood and CSF xenin are correlated with blood levels of important markers of adiposity, leptin and insulin. The levels of CSF xenin are linearly correlated with blood xenin, independently of patient body mass, suggesting that either its transport across the blood-brain barrier is not saturated in the concentration range detected in this study or that there is a coordinated release of xenin from the periphery and the CNS.
Assuntos
Barreira Hematoencefálica/metabolismo , Jejum/líquido cefalorraquidiano , Derivação Gástrica , Leptina/líquido cefalorraquidiano , Neurotensina/líquido cefalorraquidiano , Obesidade Mórbida/líquido cefalorraquidiano , Adolescente , Adulto , Transporte Biológico , Biomarcadores , Índice de Massa Corporal , Jejum/sangue , Feminino , Humanos , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Neurotensina/sangue , Obesidade Mórbida/sangue , Obesidade Mórbida/cirurgia , Radioimunoensaio , Redução de PesoRESUMO
INTRODUCTION: Several strategies on the development of radiopharmaceuticals have been employed. Bifunctional chelators seem to be a promising approach since high radiochemical yields as well as good in vitro and in vivo stability have been achieved. To date, neurotensin analogs have been radiolabeled using the (99m)Tc-carbonyl approach and none was described employing the bifunctional chelating agent technique. AIM: The purpose of this study was to evaluate the radiochemical and biological behaviour of NT(8-13) analogue radiolabeled with (99m)Tc, using HYNIC and NHS-S-acetyl-MAG(3) as chelator agents. METHODS: Radiolabeling, in vitro stability toward cysteine and glutathione, partition coefficient and plasma protein binding were assessed for both radioconjugates. Biodistribution in healthy Swiss mice were carried out in order to evaluate the biological behaviour of the radiocomplexes. RESULTS: Radiochemical yields were higher than 97% and no apparent instability toward transchelant agents was observed for both radioconjugates. A higher lipophilic character was observed for the radioconjugate labeled via MAG(3). The chelators seem to have no effect on the percentage of the radioconjugate bound to plasma proteins. A similar biological pattern was observed for both radioconjugates. Total blood, bone and muscle values revealed a slightly slower clearance for the radiocomplex labeled via MAG(3). Moreover, a remarkable liver and intestinal uptake was observed for the radiocomplex labeled via MAG(3) even at the later time points studied. CONCLUSION: The high radiochemical yields achieved and the similar in vivo pattern found for both radioconjugates make them potential candidates for imaging tumors using nuclear medicine techniques.
Assuntos
Quelantes/química , Reagentes de Ligações Cruzadas/química , Hidrazinas/química , Marcação por Isótopo/métodos , Neurotensina/química , Ácidos Nicotínicos/química , Oligopeptídeos/química , Compostos de Organotecnécio/química , Fragmentos de Peptídeos/química , Succinimidas/química , Animais , Proteínas Sanguíneas/metabolismo , Cisteína/química , Estabilidade de Medicamentos , Feminino , Glutationa/química , Camundongos , Neurotensina/sangue , Neurotensina/metabolismo , Neurotensina/farmacocinética , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/farmacocinética , RadioquímicaRESUMO
The effect of morphine (0.1 mg/kg) on insulin secretion stimulated by oral, intraduodenal, or intravenous administration of glucose was studied in seven healthy volunteers. When glucose was given intravenously, morphine had no effect on plasma glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP), or pancreatic glucagon. Following oral glucose, morphine slowed gastric emptying and reduced plasma concentrations of glucose, insulin, and GIP. During intraduodenal infusion of glucose, insulin concentrations of plasma were also decreased by morphine, an effect best explained by decreased small intestinal transit with delayed absorption of glucose and delayed release of GIP. We conclude that clinically relevant doses of morphine have no direct effect on insulin secretion and that the changes observed were secondary to slowed gastric emptying and small intestinal transit (AU)