Low cerebrospinal fluid insulin levels in obese humans.
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Adipose Tissue↗
Biomedical subjects
J Born
Publications and source records attributed to J Born.
High plasma VEGF relates to low carbohydrate intake in patients with type 2 diabetes.
OBJECTIVE: Vascular endothelial growth factor (VEGF) has been suggested to enhance glucose transport across the blood-brain barrier, thereby increasing brain glucose supply. Increased brain glucose concentration is known to suppress food intake and to decrease body mass via action on hypothalamic regulation centers. Based on the crucial role of VEGF on brain glucose supply, we hypothesized that higher VEGF concentrations are associated with lower food intake and body mass in humans. METHODS: Intending to investigate subjects with high variance of blood glucose, we examined patients with type 2 diabetes mellitus. Our hypothesis was tested in a population-based cohort of 190 subjects with type 2 diabetes. Plasma VEGF levels in conjunction with other parameters known to modulate food intake were measured and subsequently correlated with food intake patterns at a breakfast buffet as well as with body mass. RESULTS: We found that subjects with higher concentrations of plasma VEGF had 17% less carbohydrate intake (P=0.003) and 4.8% lower body mass (P=0.017) than those with lower VEGF concentrations. Intake of protein and fat did not correlate with VEGF concentrations. These associations of plasma VEGF were confirmed in multiple linear regression analyses controlling for several parameters interacting with food intake. CONCLUSION: We conclude that high plasma VEGF concentrations are associated with less carbohydrate intake and lower body mass in type 2 diabetes. The role VEGF plays in facilitating glucose access to the brain represents a new aspect of food intake regulation and energy homeostasis, with relevance for diseases with body mass disturbances.
Analysis of Variance↗
[Hydrocephalus in children].
The files of all young patients, aged from one day to 17 years, that were operated for hydrocephalus in the Service of Neurosurgery of the Citadelle Hospital from 1987 to 2003 were reviewed and analysed. Over these 16 years of practice, a shunt was placed in a total of 194 children. This paper is mainly concerned with the etiologies of hydrocephalus and the complications related to the surgical procedure.
Adolescent↗
Post-dural puncture headache in young adults: comparison of two small-gauge spinal catheters with different needle design.
BACKGROUND: To reduce the risk of post-dural puncture headache (PDPH) in continuous spinal anaesthesia, small-gauge spinal catheter systems with different techniques of dural perforation have been developed. METHODS: Two systems, the catheter through-needle technique (MicroCatheter, Portex, UK) and the catheter over-needle technique (22G Spinocath, B. Braun, Germany), were used in 18 young healthy volunteers (age 18-30 yr), who were enrolled in a neuroendocrinological investigation for analysis of neuropeptides in cerebrospinal fluid (CSF). After intermittent sampling of CSF (17 x 0.5 ml over 4 h), the catheter was removed and the development of PDPH and pain intensity were documented prospectively by the subjects in a standardized headache assessment (11-point numerical rating scale [NRS]). RESULTS: The study revealed a high overall incidence of PDPH (78%) with no significant differences between groups (P=0.26). However, the over-needle group showed a significantly shorter duration of PDPH (2.4 [SD 2.3] vs 5.1 [3.1] days, P=0.050) and lower maximum pain intensity (3.1 [2.9] vs 7.3 [3.4] NRS, P=0.014) than the through-needle group. CONCLUSIONS: The results demonstrate a potential benefit of the catheter over-needle technique for the reduction of the duration and intensity of PDPH.
Adolescent↗
Differential adaptation of neurocognitive brain functions to recurrent hypoglycemia in healthy men.
Antecedent hypoglycemia is known to attenuate hormonal and symptomatic responses to subsequent hypoglycemia. Whether this pertains also to hypoglycemia-induced cognitive dysfunction is controversially discussed. Neurocognitive adaptation might essentially depend on the type of function. Here, we compared the influence of recurrent hypoglycemia in 15 healthy men on counterregulatory hormones, subjective symptoms of hypoglycemia, short-term memory performance (word recall), and performance on an auditory attention task (oddball). The attention task was also used to record event-related brain potential (ERP) indicators of stimulus processing. In each subject, three consecutive hypoglycemic clamps were performed, two on day 1 and the third on day 2. Neurocognitive testing was performed during baseline and at two different hypoglycemic plateaus (2.8 and 2.5 mmol/l) during the first and last clamp. As expected, hormonal responses were significantly reduced to the last as compared to the first hypoglycemia indicating adaptation. Subjective symptoms also decreased in response to recurrent hypoglycemia. Short-term memory performance deteriorated distinctly on the first hypoglycemic clamp, but maintained the normal level on the last clamp (P=0.006). Likewise, the impairment in reaction time (P=0.022) and response accuracy (P=0.005) was distinctly smaller on the last than first hypoglycemia. In parallel, the hypoglycemia-induced decrease in P3 amplitude (P=0.019) and the increase in P3 latency (P=0.049) were diminished with recurrent hypoglycemia, indicating that late stages of controlled stimulus processing likewise adapted. In contrast, the distinct decrease in amplitudes of the N1 and P2 components of the ERP (preceding the P3) was closely comparable in response to the first and last hypoglycemia (P>0.3). Together results indicate an adaptation to recurrent hypoglycemia for signs of controlled stimulus processing presumably involving hippocampo-prefrontocortical circuitry, while earlier automatic stages of processing appear to be spared.
Adaptation, Psychological↗
Serum adiponectin concentrations during a 72-hour fast in over- and normal-weight humans.
OBJECTIVE: Adiponectin is currently considered an important link between obesity and insulin resistance, since circulating levels of this insulin sensitizing hormone have consistently been found to be reduced in obese subjects. However, until now it is not known how the secretion of adiponectin is regulated in response to acute metabolic changes. Here, we assessed the influence of complete fasting for 72 h on serum adiponectin levels. DESIGN: Between group comparison of repeated measurements. SUBJECTS: In total, 18 normal-weight (mean+/-s.e.m. BMI: 22.2+/-0.4 kg/m(2); age: 39.2+/-4.4 y) and nine over-weight (BMI: 33.2+/-1.8 kg/m(2); age: 36.9+/-4.5 y) subjects. MEASUREMENTS: Serum adiponectin levels were measured every 4 h during a 72-h fasting period. Additionally, concentrations of plasma glucose and serum insulin and leptin were assessed at the beginning and in the end of the fasting experiment. Insulin resistance was estimated using the homeostasis model assessment (HOMA). RESULTS: While concentrations of glucose, insulin, and leptin decreased across the fasting period by 31.0, 33.1 and 60.0%, respectively (all P<0.005), adiponectin levels remained unchanged (P=0.817). Overall, over-weight subjects exhibited slightly lower adiponectin levels than normal-weight subjects (P=0.092), but there was no difference in the time course of adiponectin levels during fasting between these two groups (P=0.970). Although, averaged adiponectin levels before and after fasting did not systematically differ, individual changes in adiponectin levels across fasting displayed a slight but significant inverse correlation with changes in plasma glucose concentration (r=-0.42, P=0.03). DISCUSSION: The data show that serum adiponectin concentrations remain remarkably stable during 72 h of fasting in normal- and over-weight subjects. Thus, adiponectin appears to reflect primarily long-term changes in body weight with little evidence for a dependence on short-term regulatory influences.
Adiponectin↗
Differential regulation of human blood glucose level by interleukin-2 and -6.
While the acute phase reaction to infection is associated with hyperglycemia, during progressing infection hypoglycemia can develop. The cytokines regulating the dynamics of host defense may concurrently contribute to blood glucose regulation. To examine this hypothesis, changes in blood glucose concentrations in healthy men were compared following administration of interleukin-2 (IL-2) and IL-6 representing, respectively, major mediators of the adaptive and the early innate immune response to bacterial infection. Doses of 10 000 IU/kg IL-2 and 0.5 microg/kg IL-6 (vs. placebo) were administered subcutaneously in two groups of men (n = 18 and 16) at 1900 h before a period of nocturnal rest allowing an assessment of changes under basal conditions. Serum concentrations of glucose and of various hormones were assessed every 60 min. Despite generally lowered glucose concentration at night, IL-2 induced a transient but distinct decrease in blood glucose concentration most consistent 8 - 9 hours following injection (p < 0.01). The hypoglycemic response to IL-2 was not accompanied by changes in serum insulin, C-peptide or cortisol. In contrast to IL-2, IL-6 led to an increase in cortisol, followed by a pronounced increase in blood glucose again peaking about 8 hours after injection (p < 0.001). Results indicate a differential regulation of blood glucose concentration by cytokines. Contrasting with the hyperglycemic effects of the acute phase regulator IL-6, the T-cell cytokine IL-2 seems to support glucose uptake and utilization by immune cells.
Adult↗
Sleep loss and the development of diabetes: a review of current evidence.
Emerging evidence suggests that short duration of sleep and sleep disturbances increase the risk of developing diabetes. The mechanism of this presumed adverse influence of sleep loss on glucose metabolism is not well understood yet. However, in diabetes research and diabetes care, the multitude of influences of sleep and sleep loss on glucose regulation has been largely neglected so far. Here, we provide a short overview of the current epidemiological and experimental evidence for a potential contribution of sleep loss to the development of diabetes.
Blood Glucose↗
Melatonin does not inhibit hypothalamic-pituitary-adrenal activity in waking young men.
The pineal hormone melatonin is mainly secreted during night-time which, in humans, is the normal time of sleep. It has been proposed that, during this period, melatonin exerts an inhibitory influence on secretory activity of the hypothalamic-pituitary-adrenal (HPA) system, although there is little evidence for this view in humans. In blind humans, a single oral dose of melatonin at bed time suppressed nocturnal cortisol secretion. However, suppression could have been secondary to an improved sleep after melatonin in these experiments. In the present study, we examined whether melatonin exerts a similar inhibitory effect on HPA activity in waking subjects. Fourteen healthy young men were tested at bed time, but kept awake throughout the experimental epoch. Thirty minutes after oral ingestion of 5 mg melatonin, activity of the HPA-system was stimulated through a standard insulin-induced hypoglycaemia. Adrenocorticotrophin hormone and cortisol concentrations under basal conditions before insulin injection, as well as in response to insulin-induced hypoglycaemia, were almost identical for the melatonin and placebo control conditions (P > 0.5). However, melatonin increased plasma prolactin concentrations (P < 0.01) and reduced systolic blood pressure in the time interval following hypoglycaemia (P < 0.05). Based on a review of the literature and our results, we conclude that melatonin per se has no substantially suppressing effect on HPA secretory activity, although such an effect can be gated by sleep-related processes.
Adult↗
Antecedent hypoglycaemia attenuates vascular endothelial growth factor response to subsequent hypoglycaemia in healthy men.
AIM: The plasma concentration of vascular endothelial growth factor (VEGF) has recently been shown to increase sharply in response to hypoglycaemia and, thus, has been proposed as having a role in hypoglycaemia counter-regulation. Many counter-regulatory hormones show a reduced response after antecedent hypoglycaemia. We therefore investigated whether this decrease in responsiveness with repetitive hypoglycaemia also pertains to VEGF. METHODS: Three hypoglycaemic clamp experiments were performed on two consecutive days in 15 healthy men. VEGF response was assessed during the first and last hypoglycaemic period. RESULTS: As expected, plasma VEGF concentrations rose markedly during the clamps (P < 0.001). The increase was distinctly blunted during the third (+13 +/- 8 pg/ml) as compared with the first (+54 +/- 18 pg/ml) hypoglycaemic clamp (P = 0.046). CONCLUSION: This data confirms that circulating VEGF concentrations increase acutely during hypoglycaemia. Like the counter-regulatory hormones, the hypoglycaemia-induced rise in VEGF is attenuated after antecedent hypoglycaemia. The origin of increased systemic VEGF concentration during hypoglycaemia and its physiological role remains to be defined.
Adult↗
A regulatory role of prolactin, growth hormone, and corticosteroids for human T-cell production of cytokines.
The release of the pituitary hormones, prolactin and growth hormone (GH), and of adrenal corticosteroids is subject to a profound regulation by sleep. In addition these hormones are known to be involved in the regulation of the immune response. Here, we examined their role for in vitro production of T-cell cytokines. Specifically, we hypothesized that increased concentrations of prolactin and GH as well as a decrease in cortisol, i.e., hormonal changes characterizing early nocturnal sleep, could be responsible for a shift towards T helper 1 (Th1) cytokines during this time. Whole blood was sampled from 15 healthy humans in the morning after regular sleep and was activated in vitro with ionomycin and two concentrations of phorbol myrestate acetate (PMA, 8 and 25 ng/ml) in the absence or presence of prolactin, prolactin antibody, GH, glucocorticoid receptor (GR) antagonist RU-486, or mineralocorticoid receptor (MR) antagonist spironolactone. Hormones were examined at physiological concentrations. Production of T-cell derived cytokines was measured at the single cell level using multiparametric flow cytometry. Generally, effects were more pronounced after stimulation with 8 rather than 25 ng/ml PMA. The following changes reached significance (p <.05): prolactin (versus prolactin antibody) increased tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) producing CD4+ and CD8+ cells and interleukin-2 (IL-2) producing CD8+ cells. Compared with control, prolactin antibody decreased, whereas GH increased IFN-gamma+CD4+ cells. RU-486 increased TNF-alpha, IFN-gamma, and IL-2 producing CD4+ and CD8+ cells. Surprisingly strong effects were found after MR blocking with spironolactone which increased TNF-alpha, IFN-gamma, and IL-2 producing CD4+ and CD8+ cells. No effects on IL-4+CD4+ cells were observed, while the IFN-gamma/IL-4 ratio shifted towards Th1 after spironolactone and after RU-486 plus GH. Results suggest that enhanced prolactin and GH concentrations as well as low cortisol levels during early nocturnal sleep synergistically act to enhance Th1 cytokine activity.
Adrenal Cortex Hormones↗
The selfish brain: competition for energy resources.
The brain occupies a special hierarchical position in the organism. It is separated from the general circulation by the blood-brain barrier, has high energy consumption and a low energy storage capacity, uses only specific substrates, and it can record information from the peripheral organs and control them. Here we present a new paradigm for the regulation of energy supply within the organism. The brain gives priority to regulating its own adenosine triphosphate (ATP) concentration. In that postulate, the peripheral energy supply is only of secondary importance. The brain has two possibilities to ensure its energy supply: allocation or intake of nutrients. The term 'allocation' refers to the allocation of energy resources between the brain and the periphery. Neocortex and the limbic-hypothalamus-pituitary-adrenal (LHPA) system control the allocation and intake. In order to keep the energy concentrations constant, the following mechanisms are available to the brain: (1) high and low-affinity ATP-sensitive potassium channels measure the ATP concentration in neurons of the neocortex and generate a 'glutamate command' signal. This signal affects the brain ATP concentration by locally (via astrocytes) stimulating glucose uptake across the blood-brain barrier and by systemically (via the LHPA system) inhibiting glucose uptake into the muscular and adipose tissue. (2) High-affinity mineralocorticoid and low-affinity glucocorticoid receptors determine the state of balance, i.e. the setpoint, of the LHPA system. This setpoint can permanently and pathologically be displaced by extreme stress situations (chronic metabolic and psychological stress, traumatization, etc.), by starvation, exercise, infectious diseases, hormones, drugs, substances of abuse, or chemicals disrupting the endocrine system. Disorders in the 'energy on demand' process or the LHPA-system can influence the allocation of energy and in so doing alter the body mass of the organism. In summary, the presented model includes a newly discovered 'principle of balance' of how pairs of high and low-affinity receptors can originate setpoints in biological systems. In this 'Selfish Brain Theory', the neocortex and limbic system play a central role in the pathogenesis of diseases such as anorexia nervosa and obesity.
Adaptation, Physiological↗
Glucocorticoids and melanocortins in the regulation of body weight in humans.
The last decade witnessed a dramatic increase in knowledge concerning regulation of body weight and obesity. According to recent concepts constancy of body weight is a side product of regulatory events which ensure constant glucose fluxes to the brain. Within these control systems glucocorticoids and melanocortins play a fundamental role at several sites. The melanocortin neurons in the arcuate nucleus are important mediators of the feedback effects of leptin and insulin. Glucocorticoid and mineralocorticoid receptors in hippocampal neurons are crucial as they define the balance between glucose allocation processes and food intake. Thereby, the hippocampal structures determine the setpoint for bodyweight regulation. Novel approaches to treatment of obesity must aim at manipulating these brain structures.
Arcuate Nucleus of Hypothalamus↗
Spindle and slow wave rhythms at slow wave sleep transitions are linked to strong shifts in the cortical direct current potential.
Electroencephalographic activity at the transition from wakefulness to sleep is characterized by the appearance of spindles (12-15 Hz) and slow wave rhythms including delta activity (1-4 Hz) and slow oscillations (0.2-1 Hz). While these rhythms originate within neocortico-thalamic circuitry, their emergence during the passage into slow wave sleep (SWS) critically depends on the activity of neuromodulatory systems. Here, we examined the temporal relationships between these electroencephalogram rhythms and the direct current (DC) potential recorded from the scalp in healthy men (n=10) using cross-correlation analyses. Analyses focused on transitions from wakefulness to SWS in the beginning of the sleep period, and from SWS to lighter sleep and rapid eye movement (REM) sleep at the end of the first sleep cycle. For spindle, delta and slow oscillatory activity strong negative correlations with the DC potential were found at the transition into SWS with peak correlation coefficients (at zero time lag) averaging r=-0.81, -0.88 and -0.88, respectively (P<0.001). Though slightly lower, distinct negative correlations between these measures were also found at the transition from SWS to REM sleep (-0.78, -0.77 and -0.77, respectively, P<0.001). Fast oscillatory activity in the beta frequency band (15-25 Hz) was correlated positively with the DC potential (r=+0.75, P<0.05, at the passage to SWS). Data indicate close links between increasing spindle, delta and slow oscillatory activity and the occurrence of a steep surface negative cortical DC potential shift during the transition from wake to SWS. Likewise, a DC potential shift toward surface positivity accompanies the disappearance of these oscillatory phenomena at the end of the non-REM sleep period. The DC potential shifts may reflect gradual changes in extracellular ionic (Ca2+) concentration resulting from the generation of spindle and slow wave rhythms, or influences of neuromodulating systems on cortical excitability thereby controlling the emergence of cortical spindle and slow wave rhythms at SWS transitions.
Adult↗
NPY attenuates positive cortical DC-potential shift upon food intake in man.
Previous studies have shown that the regulation of hunger and satiety is accompanied by coordinate changes in cortical excitability. Starved subjects show a transient negative shift in the scalp-recorded cortical direct current (DC-)potential in the beginning of eating, indicating increased cortical excitability. With increasing satiety, the DC negativity becomes soon replaced by a reward related positive potential shift. Neuropeptide Y (NPY) is known from animal studies to increase food intake and induce weight gain, which might result from increasing hunger drive or reducing satiety. Here we investigated whether NPY affects the cortical sequelae of hunger and satiety regulation as reflected by cortical DC-potentials in man. DC-potentials were recorded over frontal (Fz, F3, F4), central (Cz, C3, C4) and parietal (Pz, P3, P4) electrode positions in 14 subjects who had abstained from eating for 15 h and who were intranasally administered 50 nmol of NPY and placebo 20 min prior to recordings. After a 3-min baseline epoch, subjects consumed 400 ml of liquid food within 5 min. Recordings ended 7 min after food consumption. In the placebo condition during food intake, with some delay a positive DC-potential shift developed which was most pronounced over frontal and central areas and reached maximum values 0-3 min after food consumption. NPY reduced this satiation associated positive shift (p<0.05) over all areas except P3 and Pz. Data suggest that NPY exerts its orexigenic influence by attenuating mechanisms of satiation.
Adult↗
Sexual conflict in Sepsis cynipsea: female reluctance, fertility and mate choice.
Sexual conflict can elevate mating costs via male inflicted damage to females. Possible selective advantages to males include decreasing the likelihood that females remate and/or increasing females' current reproductive investment in a manner analogous to terminal reproductive investment. We investigated female mating behaviour relative to their number of previous copulations in the fly Sepsis cynipsea, and whether males accepted as first mates were more likely to be accepted again. Females were more likely to remate with new rather than original males, although there was no associated fitness benefit, and in contrast to theoretical predictions, females became less reluctant to remate as the number of previous copulations increased. Additionally, females did not increase reproductive investment as would be expected if they were ensuring their final reproductive efforts were maximized by remating. This suggests that damaging females is a pleiotropic effect which inadvertently leads to increased, not decreased, polyandry.
Animals↗
EEG synchronization upon reward in man.
OBJECTIVES: It was tested whether reward in humans is associated with EEG synchronization similar to that seen in animals. METHODS: In two experiments (I and II) the EEG was recorded from frontal, central, and parietal positions before, during, and after drinking or oral stimulation. In Experiment I, subjects (n=11) who had either been thirsty for 16h or had quenched thirst before recordings, drank 400ml of water. In Experiment II, thirsty subjects (n=11) either drank 400ml of water or sucked on a soother. The recording epochs included a 3min baseline, an interval of about 5min during which subjects drank or sucked on the soother, and a 7min post-drinking interval. RESULTS: During the drinking epoch, beta band-power (12-30Hz) was enhanced in both conditions of Experiment I and II, respectively. In Experiment I, after drinking, lower alpha power (8-10Hz) was higher when subjects were thirsty than when they were not. Lower alpha was also enhanced in the post-drinking interval of both conditions of Experiment II, and after sucking, lower alpha synchronization was in addition accompanied by increased theta activity (4-8Hz). CONCLUSIONS: Increased beta activity during drinking and sucking in thirsty subjects presumably reflects non-specific activation related to the motivational strength of sensorimotor regulation during consumatory behavior. The thirst dependent lower alpha synchronization after drinking, generated not only by water consumption but also by surrogate oral stimuli, can be considered a reflection of the drive reducing and rewarding qualities of oral stimulation and consumatory behavior.
Adult↗
The effect of experimentally induced insulin resistance on the leptin response to hyperinsulinaemia.
OBJECTIVE: Insulin is thought to be an important regulator of leptin secretion. However, increasing evidence suggests that insulin-mediated glucose uptake rather than insulin per se regulates circulating leptin concentration. Here, we hypothesised that a reduction of insulin sensitivity, ie insulin resistance, will diminish the stimulatory effect of insulin on leptin secretion as a consequence of decreased insulin-mediated glucose uptake. DESIGN: Changes in serum leptin concentration during 30 hyperinsulinaemic-hypoglycaemic clamps were studied after induction of different levels of insulin resistance in normal-weight men. In 15 subjects insulin sensitivity was reduced by exposing them to a 2.5 h antecedent hypoglycaemia (3.1 mmol/l) induced by a high rate of insulin infusion (15.0 mU/min/kg) on the day before the proper experiment ('ante-hypo' condition). In the other 15 subjects no antecedent hypoglycaemia was induced ('control' condition). The proper experiment on both conditions was a 6 h stepwise hypoglycaemic clamp induced by a constant rate of insulin infusion (1.5 mU/min/kg). SUBJECTS: Experiments were carried out in 30 lean healthy subjects (age, mean +/- s.e.m., 26 +/- 1 y; body mass index, 23.1 +/- 0.6 kg/m2). RESULTS: As expected, glucose demand during the clamp was lower in the ante-hypo condition than in the control condition (gram of glucose infused per kilogram body weight, 1.52 +/- 0.16 vs 2.01 +/- 0.17 g/kg; P < 0.05). During the clamp, leptin levels increased by 25.4 +/- 4.3% in the control condition (P < 0.05), but not in the ante-hypo condition (+4.8 +/- 4.5%; P > 0.25). Thus, serum leptin response to the clamp significantly differed between the two conditions (P < 0.01). Across both conditions, the increase of leptin levels during the clamp was correlated with the amount of glucose infused (r = 0.37; P < 0.05). CONCLUSION: Considering that insulin concentrations were identical during both clamp conditions, the data indicate that experimentally-induced insulin resistance diminishes the stimulatory effect of insulin on leptin secretion.
Adult↗