Subject(s)
Humans , Male , Female , Middle Aged , Intensive Care Units , Primary Health Care , Patient Discharge , Palliative Care , Critical Illness , Frail ElderlyABSTRACT
Leptin and somatostatin (SRIF) have opposite effects on food seeking and ingestive behaviors, functions partially regulated by the frontoparietal cortex and hippocampus. Although it is known that the acute suppression of food intake mediated by leptin decreases with time, the counter-regulatory mechanisms remain unclear. Our aims were to analyze the effect of acute central leptin infusion on the SRIF receptor-effector system in these areas and the implication of related intracellular signaling mechanisms in this response. We studied 20 adult male Wister rats including controls and those treated intracerebroventricularly with a single dose of 5 µg of leptin and sacrificed 1 or 6h later. Density of SRIF receptors was unchanged at 1h, whereas leptin increased the density of SRIF receptors at 6h, which was correlated with an elevated capacity of SRIF to inhibit forskolin-stimulated adenylyl cyclase activity in both areas. The functional capacity of SRIF receptors was unaltered as cell membrane levels of αi1 and αi2 subunits of G inhibitory proteins were unaffected in both brain areas. The increased density of SRIF receptors was due to enhanced SRIF receptor subtype 2 (sst2) protein levels that correlated with higher mRNA levels for this receptor. These changes in sst2 mRNA levels were concomitant with increased activation of the insulin signaling, c-Jun and cyclic AMP response element-binding protein (CREB); however, activation of signal transducer and activator of transcription 3 was reduced in the cortex and unchanged in the hippocampus and suppressor of cytokine signaling 3 remained unchanged in these areas. In addition, the leptin antagonist L39A/D40A/F41A blocked the leptin-induced changes in SRIF receptors, leptin signaling and CREB activation. In conclusion, increased activation of insulin signaling after leptin infusion is related to acute up-regulation of the SRIF receptor-effector system that may antagonize short-term leptin actions in the rat brain.
Subject(s)
Brain/metabolism , Insulin/metabolism , Leptin/metabolism , Receptors, Somatostatin/biosynthesis , Signal Transduction/physiology , Animals , Blotting, Western , Brain/drug effects , Enzyme-Linked Immunosorbent Assay , Immunoassay , Injections, Intraventricular , Leptin/administration & dosage , Male , Rats , Rats, Wistar , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Somatostatin/metabolism , Up-RegulationABSTRACT
Introducción: Los inmunoensayos múltiples permiten la valoración simultánea de diferentes variables en volúmenes reducidos de muestras biológicas. Nuestro objetivo ha sido establecerlos valores normales de citocinas e insulina durante el desarrollo puberal, así como su relación con esteroides adrenales y gonadales. Sujetos y métodos: Se estudiaron las concentraciones séricas de insulina, adiponectina, resistina, leptina, factor de necrosis tumoral-α, interleucina-1β, interleucina-6 e interleucina-8 en 147 niños sanos (Tanner I, 18 varones y 18 mujeres; Tanner II, 17 varones y 13 mujeres; Tanner III y IV, 21 varones y 19 mujeres, y Tanner V, 18 varones y 23 mujeres). Además, se analizó la relación de estas variables con las concentraciones de testosterona total y libre, estradiol, proteína transportadora de los esteroides sexuales, 17-hidroxiprogesterona, sulfato de dehidroepiandrosterona, glucurónido de 3 α -androstanodiol y Δ4-androstendiona. Resultados: Las concentraciones de insulina, resistina y leptina se incrementaron durante el desarrollo, y son superiores en mujeres, mientras que las de adiponectina no se modificaron, aunque son también mayores en mujeres que en varones. Los niveles de interleucina-6 y 8 aumentaron y los de interleucina-1β disminuyeron, sin presentar dimorfismo sexual. Existe una buena correlación entre adiponectina y proteína transportadora de los esteroides sexuales, así como entre leptina y Δ 4-androstendiona. Conclusiones: Las variaciones de estos parámetros parecen estar relacionadas con la función adrenal y gonadal. Por este motivo, para la utilización de los datos de normalidad de las citocinas en la infancia y adolescencia mediante inmunoensayo múltiple debe tenerse en cuenta el estadio puberal y el sexo (AU)
Introduction: Multiplexed immunoassays allow the simultaneous determination of multiple parameters from minute biological samples. Our aim was to establish the normal values of cytokines and insulin during pubertal development, as well as their relationship with adrenal and gonadal steroids. Subjects and methods: Serum insulin, adiponectin, resistin, leptin, tumoral necrosis factor-α, interleukin-1β, interleukin-6 and interleukin-8 concentrations were studied in 147 healthy children (Tanner I, 18 males and 18 females; Tanner II, 17 males and 13 females; Tanner III and IV, 21 males and 19 females and Tanner V, 18 males and 23 females). The relationship of these parameters with free and total testosterone, estradiol, sex-hormone binding globulin, 17-hidroxyprogesterone, dehydroepiandrosterone sulphate, 3 α -androstanediol glucuronide and Δ 4-androstenedione levels were also analyzed. Results: The concentrations of insulin, resistin and leptin increased during development, with higher levels found in females. Adiponectin levels did not change, although higher concentrationswere also observed in females than in males. Interleukin-6 and 8 increased andinterleukin-1β levels decreased throughout development, without any evidence of sexual dimorphism. There are good correlations between adiponectin and sex-hormone binding globulin, as well as between leptin and Δ 4-androstenedione.Conclusions: Changes in these parameters seem to be related with adrenal and gonadal function. Pubertal stage and sex must be taken into consideration when these data are used (AU)
Subject(s)
Humans , Male , Female , Child , Adolescent , Immunoassay/methods , Insulin/analysis , Cytokines/analysis , Adiponectin/analysis , Leptin/analysis , Resistin/analysis , Tumor Necrosis Factor-alpha/analysis , Interleukins/analysis , Reference ValuesABSTRACT
INTRODUCTION: Multiplexed immunoassays allow the simultaneous determination of multiple parameters from minute biological samples. Our aim was to establish the normal values of cytokines and insulin during pubertal development, as well as their relationship with adrenal and gonadal steroids. SUBJECTS AND METHODS: Serum insulin, adiponectin, resistin, leptin, tumoral necrosis factor-α, interleukin-1ß, interleukin-6 and interleukin-8 concentrations were studied in 147 healthy children (Tanner I, 18 males and 18 females; Tanner II, 17 males and 13 females; Tanner III and IV, 21 males and 19 females and Tanner V, 18 males and 23 females). The relationship of these parameters with free and total testosterone, estradiol, sex-hormone binding globulin, 17-hydroxyprogesterone, dehydroepiandrosterone sulphate, 3α-androstanediol glucuronide and Δ4-androstenedione levels were also analyzed. RESULTS: The concentrations of insulin, resistin and leptin increased during development, with higher levels found in females. Adiponectin levels did not change, although higher concentrations were also observed in females than in males. Interleukin-6 and 8 increased and interleukin-1ß levels decreased throughout development, without any evidence of sexual dimorphism. There are good correlations between adiponectin and sex-hormone binding globulin, as well as between leptin and Δ4-androstenedione. CONCLUSIONS: Changes in these parameters seem to be related with adrenal and gonadal function. Pubertal stage and sex must be taken into consideration when these data are used.
