Modeling the Effect of Spontaneous Activity on Core Temperature in Healthy Human Subjects

Nine healthy females were studied about the time of the spring equinox, while living in student accommodation and aware of the passage of solar time. After 7 control days, during which a conventional lifestyle was lived, subjects underwent a 24-h 'constant routine', followed by 17 'days' on a 27-h 'day' (9 h sleep and 18 h wake). Throughout the experiment, regular recordings of (non-dominant) wrist activity (every 30 s) and rectal temperature (every 6 min) were made. Only the control and 27-h (experimental) 'days' have been analysed in the present report. From each subject, 24-h profiles of raw temperature (consisting of 240 points) were obtained: one (control days), by averaging the control days; the other (experimental days), by conflating 16 consecutive 27-h 'days'. Activity data were first collected into 240 points by summing them over 6-min intervals; they were then converted into three data sets (each of 240 points) for control and, separately, for experimental days. These data sets were summed activities in the previous 18 min (A18), summed activity over the previous 18-30 min (A30), and summed activity over the previous 30-42 min (A42). The raw temperature data sets for control and experimental days were sepa-rately analysed by ANCOVA using two time-of-day factors: 'hours' (24 levels) and 'six-minute-intervals' (10 levels). The covariate was the three activity data sets; in order to make the analysis more versatile, a cubic polynomial model was used, with a linear, quadratic and cubic term for each of these activity data sets. Moreover, the effects of activity upon core temperature were separately assessed for four 6-h sections of the 24-h profile, centred on its low, rising, high and falling phases. The main results were as follows: 1. All three activity data sets made significant contributions to the model, but that by the A30 data set was the most powerful of the three. This supports the use of activity files covering the previous 30 min in other 'purification' methods. 2. Although the linear term was the one that was significant most frequently, quadratic and (negative) cubic terms were also present on several occasions. This result indicates that the effect of activity upon core temperature can be approximated by a linear function (as has been done in other 'purification' models), but that, with wider ranges of activity, a sigmoid curve would be more accurate, indicative of the process of thermoregulation. 3. During the experimental days, the effect of activity upon temperature was greater in the rising than the falling temperature phase, and greater in the low than in the high phase. These results are predicted from current understanding of the circadian rhythm of thermoregulation. 4. During control days, the effects of activity were more complex, probably due to the factors that were present at some, but not all, phases — factors such as sleep, meals, changes in posture, lighting, and so on. 5. The ANCOVA also enabled the temperature profiles, corrected for the effects of activity (and, therefore, to be considered as 'purified'), to be displayed. We conclude that the use of ANCOVA to tackle the problem of 'purifying' raw temperature data is a promising one. So far, it has produced results that accord with those from other 'purification' methods and with predictions based on our current understanding of the circadian rhythm of thermoregulation.     

Zinc acutely and temporarily inhibits adrenal cortisol secretion in humans

Hypo- and hyperzincemia has been reported to cause alterations in the adrenal secretion. To determine the acute effect of zinc on cortisol levels, we studied 27 normal individuals of both sexes aged 20-27 y after a 12-h fast. The tests were initiated at 7:00 AM when an antecubital vein was punctured and a device for infusion was installed and maintained with physiological saline. Zinc was administered orally at 8:00 AM. Subjects were divided into an experimental group of 13 individuals who received doses of 25, 37.5, and 50 mg of zinc and a control group of 14 individual who received 20 mL of physiological saline. Serial blood samples were collected over a period of 240 min after basal samples (-30 and 0 min). We detected an acute inhibitory effect of zinc on cortisol secretion during 240 min of the study period in the experimental group.     

Light-dark differences in the effects of ambient temperature on gaseous metabolism in newborn rats.

Body temperature (T(b)) of rat pups (7-9 days old) raised under a 12:12-h light-dark (L-D) regimen (L: 0700-1900, D: 1900-0700) was consistently higher in D than in L by approximately 1.1 degrees C. We tested the hypothesis that the L-D differences in T(b) were accompanied by differences in the set point of thermoregulation. Measurements were performed on rat pups at 7-9 days after birth. O(2) consumption (VO(2)) and CO(2) production (VCO(2)) were measured with an open-flow method during air breathing, as ambient temperature (T(a)) was decreased from 40 to 15 degrees C at the constant rate of 0.5 degrees C/min. At T(a) >/=33 degrees C, VO(2) was not significantly different between L and D, whereas VCO(2) was higher in L, suggesting a greater ventilation. Over the 33 to 15 degrees C range the VO(2) values in D exceeded those in L by approximately 30%. Specifically, the difference was contributed by differences in thermogenesis at T(a) = 30 to 20 degrees C. As T(a) was decreased, the critical temperature at which VO(2) began to rise was lower in L. We conclude that the higher T(b) of rat pups in D is accompanied by a higher set point for thermoregulation and a greater thermogenesis. These results are consistent with the idea that, in newborns, endogenous changes in the set point of thermoregulation contribute to the circadian oscillations of T(b).     

The development of mating propensity in two karyotypes of Drosophila persimilis

Progeny from twenty homokaryoptypic strain crosses (ten each for KL and MD arrangements of Drosophila persimilis from Humboldt County, California) were tested for time (days) from eclosion to onset of mating activity (‘switch-on’ of female receptivity). Identically-aged flies on days 1, 2, 3 and 4 following eclosion were introduced into plastic chambers and observed for 30 min, ten pairs per chamber and 100 pairs per cross. Percentages of mating in 30 min (mating activity) and in the first 5 min (mating speed) were recorded. Of the twenty crosses, four of KL and one of MD failed to achieve a level of mating attained by the remaining fifteen ‘normals’ so that switch-on was not ascertainable from them. Among normals, however, KL was significantly higher in mating activity on day 2 than MD, but cumulative total matings caught up in MD so that by day 4 there was no difference between karyotypes. Mating speed was low on day 2 but increased variably on days 3 and 4. Reciprocal age tests ruled out increase in male courtship after day 2 but suggested a decrease in threshold level of females (courtship summation), A positive regression between mating speed and activity on days 3 and 4 suggested that switch-on and courtship summation may not be under independent genetic control.     

Behavioural and autonomic thermoregulation in lean and genetically obese (ob/ob) mice

1. 1.|The capacity for behavioural thermoregulation has been assessed in lean and genetically obese (ob/ob) mice, using operant conditioning.

2. 2.|After 30 min at an initial air temperature (T_a) of 0°C, total thermal reinforcements and T_a were greater in ob/ob than lean mice; deep body temperature increased in both genotypes. Without a heater, body temperature in the ob/ob fell markedly in the cold.

3. 3.|Behavioural thermoregulation also depended on food intake and test temperature. i]4.|The capacity for behavioural thermoregulation is thus unimpaired in the ob/ob mouse, unlike that for autonomic thermoregulation, suggesting separate sets of central controls for the two thermoregulatory systems.

A dynamic inline sample thermoregulation unit for flow cytometry

BACKGROUND: Flow cytometry is a valuable tool for the study of cellular and molecular interactions. We sought to develop instrumentation that would allow accurate and precise inline dynamic temperature control of flow cytometry samples in order to expand the analytical capabilities of flow cytometry. METHODS: Using a temperature controller, DC power supply, and a Peltier module, we designed a temperature control circuit that regulates the temperature of a heat transfer block. The heat transfer block surrounds the sample line to efficiently heat and cool the sample. We attached DNA oligomers to microspheres and observed the denaturation of fluorescently labeled complementary oligomers to verify that the sample was achieving the desired temperature. RESULTS: The inline thermoregulation unit can ramp between 30 and 95 degrees C (>2 degrees C per second) within 30 s repeatedly. The accuracy of the instrument was verified by comparing the observed melting temperatures of the oligomer sets to the predicted values. These values varied within 6% of the predicted and were reproducible over a variety of conditions. CONCLUSIONS: The apparatus we constructed accurately and dynamically controls the sample temperature of inline samples. Flow cytometers equipped with our inline thermoregulation unit will be able to conveniently use temperature as a robust experimental parameter.     

Orientation behaviour in the Grayling butterfly: thermoregulation or crypsis?

ABSTRACT.

• 1 Body orientation and wing tilting in Hipparchia semele (L.) have been explained previously both by the need for shadow-minimization (crypsis hypothesis) and by the need to regulate body temperature (thermoregulation hypothesis).
• 2 This study tests the thermoregulation hypothesis by quantifying butterfly orientation in relation to sun position, using vector analysis, and correlating the data with ambient temperature and time of day.
• 3 During sunshine, Graylings tend to present a maximal wing area to the sun's rays when the ambient temperature is relatively low, and a minimal area when it is high ('sunning’and‘heat-avoiding’positions respectively).
• 4 On cool sunny days, butterflies adopt sunning positions throughout the day, whereas on warm sunny days they adopt sunning positions during the outlying periods and heat-avoiding positions in the middle period of the day. Correlations between wing exposure and both ambient temperature and time of day are statistically significant for warm sunny days.
• 5 During overcast weather, butterfly orientation is very variable and possibly random.
• 6 Analysis of sunny day data supports the thermoregulation hypothesis. This is discussed in relation to other known types of thermoregulatory behaviour observed in this species: stilting, shade-seeking, ground-hugging and shivering.
• 7 Conversely, the results do not support the crypsis hypothesis.

     

Genetic parameters for thermoregulation and production traits in lactating sows reared in tropical climate

The objective of this study was to estimate the genetic parameters for thermoregulation traits and the relationships with performance of Large White lactating sows reared in a tropical humid climate. The thermoregulation traits were rectal temperature (RT), cutaneous temperature (CT) and respiratory rate (RR) during lactation measured in the afternoon (1200 h) and in the morning (0700 h). The production traits were sow’s average daily feed intake (ADFI), litter BW gain (LBWg) and sow’s proportion of BW change between farrowing and weaning (BWc). Complete data included 931 lactating performance on 329 Large White sows from the INRA experimental unit in Guadeloupe (French West Indies). Random regression models using linear spline functions were used for longitudinal data (RT, CT, RR and daily feed intake). Results showed that when ignoring values at the beginning and the end of lactation, the traits studied can be treated as the same trait throughout days of lactation, with fairly constant heritability and variance. However, largest heritabilities and genetic variances were estimated in mid-lactation. Heritability estimates on average performance during lactation were low to moderate for thermoregulation traits (0.35±0.09 for RT, 0.34±0.12 for CT and 0.39±0.13 for RR). Heritability estimates for production traits were 0.26±0.08 for ADFI, 0.20±0.07 for BWc and 0.31±0.09 for LBWg. Significant genetic correlations between thermoregulation traits and production traits were only obtained for ADFI and RR (0.35±0.12). From this study it can be concluded that thermoregulation traits are heritable, indicating that there are genetic differences in heat stress tolerance in lactating Large White sows.     

Temperature acclimation and phospholipid phase transition in hypothalamic membrane phospholipids of garden lizard, Calotes versicolor

Garden lizards, Calotes versicolor, were acclimated to three different temperatures, i.e., 16°C, 26°C and 36°C for a period of 30 days in ‘walk-in-environmental chambers’. The phospholipid profile and fatty acid pattern were analysed in the hypothalamus and brain of the acclimated animals. Hypothalamic and brain membrane phospholipids were prepared and their phase-transition temperatures were recorded using differential scanning calorimetry. Acclimation temperature, phospholipid composition, fatty acids of these phospholipids and the physical state and fluidity of the specific model membranes of hypothalamus (and brain) are intimately inter-related. Evidence is presented for the first time to show a possible correlation between acclimation temperature and phase-transition temperature of hypothalamic phospholipid membrane. A direct physico-chemical basis is suggested for the thermoregulatory process of hypothalamus leading to a better understanding of our knowledge on the origin of thermoregulation.     

Waking and Sleeping following Water Deprivation in the Rat

Wake-sleep (W-S) states are affected by thermoregulation. In particular, REM sleep (REMS) is reduced in homeotherms under a thermal load, due to an impairment of hypothalamic regulation of body temperature. The aim of this work was to assess whether osmoregulation, which is regulated at a hypothalamic level, but, unlike thermoregulation, is maintained across the different W-S states, could influence W-S occurrence. Sprague-Dawley rats, kept at an ambient temperature of 24°C and under a 12 h∶12 h light-dark cycle, were exposed to a prolonged osmotic challenge of three days of water deprivation (WD) and two days of recovery in which free access to water was restored. Two sets of parameters were determined in order to assess: i) the maintenance of osmotic homeostasis (water and food consumption; changes in body weight and fluid composition); ii) the effects of the osmotic challenge on behavioral states (hypothalamic temperature (Thy), motor activity, and W-S states). The first set of parameters changed in WD as expected and control levels were restored on the second day of recovery, with the exception of urinary Ca⁺⁺ that almost disappeared in WD, and increased to a high level in recovery. As far as the second set is concerned, WD was characterized by the maintenance of the daily oscillation of Thy and by a decrease in activity during the dark periods. Changes in W-S states were small and mainly confined to the dark period: i) REMS slightly decreased at the end of WD and increased in recovery; ii) non-REM sleep (NREMS) increased in both WD and recovery, but EEG delta power, a sign of NREMS intensity, decreased in WD and increased in recovery. Our data suggest that osmoregulation interferes with the regulation of W-S states to a much lesser extent than thermoregulation.     

Peroxidase and chitinase isoenzyme activities during root infection of Chinese cabbage with Plasmodiophora brassicae

Roots of two Chinese cabbage (Brassica campestris L. ssp. pekinensis) varieties, one tolerant and one susceptible, were inoculated with Plasmodiophora brassicae in liquid medium and in soil. Chitinase and peroxidase activities were determined in roots and shoots 1–21 days after inoculation with resting spores of Plasmodiophora and the enzyme activities compared with healthy tissue of the same age. In infected roots of the susceptible variety ‘Granat’ chitinase activity was higher than in the control 10 days after inoculation with spores. In the tolerant variety ‘Parkin’ we detected an increase in chitinase activity at the same time, which was about twice that of ‘Granat’. Chitinase activity in ‘Granat’ was also enhanced on day 13, 14 and 17 after inoculation, whereas chitinase activity in ‘Parkin’ was lower in the infected roots than in the controls during that period. In the shoots no correlation between chitinase activity and infection in the two varieties was observed. Chitinase from Chinese cabbage was further characterized and showed a pH optimum at pH 4.5–5.5 and a temperature optimum at 35–45°C. After isoelectric focusing 7 isoenzymes were discovered, but there were almost no differences between infected and healthy root extracts. Two isoenzymes with pI 8.7 and 8.8 showed cross-reactivity with an antiserum against bean chitinases. The molecular mass of these isoenzymes was determined as 33 kDa. Total peroxidase activity was generally higher in root tissue of both varieties than in the shoots. Peroxidase activity was increased most prominently in infected ‘Granat’ roots on day 13 after inoculation and of both varieties on day 17 compared to the controls. In clubbed tissue of ‘Granat’ a specific peroxidase isoenzyme appeared the first time 21 days after inoculation and was most prominent 28–30 days after inoculation. This isoenzyme had a molecular mass of ca 24 kDa and a pI of ca 8.8. With respect to our results the strategy of the Plasmodiophorales for plant attack is discussed.     

Incorporating neurophysiological concepts in mathematical thermoregulation models

Skin blood flow (SBF) is a key player in human thermoregulation during mild thermal challenges. Various numerical models of SBF regulation exist. However, none explicitly incorporates the neurophysiology of thermal reception. This study tested a new SBF model that is in line with experimental data on thermal reception and the neurophysiological pathways involved in thermoregulatory SBF control. Additionally, a numerical thermoregulation model was used as a platform to test the function of the neurophysiological SBF model for skin temperature simulation. The prediction-error of the SBF-model was quantified by root-mean-squared-residual (RMSR) between simulations and experimental measurement data. Measurement data consisted of SBF (abdomen, forearm, hand), core and skin temperature recordings of young males during three transient thermal challenges (1 development and 2 validation). Additionally, ThermoSEM, a thermoregulation model, was used to simulate body temperatures using the new neurophysiological SBF-model. The RMSR between simulated and measured mean skin temperature was used to validate the model. The neurophysiological model predicted SBF with an accuracy of RMSR?<?0.27. Tskin simulation results were within 0.37 °C of the measured mean skin temperature. This study shows that (1) thermal reception and neurophysiological pathways involved in thermoregulatory SBF control can be captured in a mathematical model, and (2) human thermoregulation models can be equipped with SBF control functions that are based on neurophysiology without loss of performance. The neurophysiological approach in modelling thermoregulation is favourable over engineering approaches because it is more in line with the underlying physiology.     

Modification of spontaneous activity patterns in the malaria vector Anopheles gambiae sensu stricto when presented with host‐associated stimuli

Anopheles gambiae sensu stricto Giles (Diptera: Culicidae) is the main malaria vector in sub‐Saharan Africa. Mated females show a circadian rhythm of spontaneous activity under constant environmental conditions that extends across the scotophase (subjective night). The effect of host‐associated cues [i.e. human foot odour supplemented with carbon dioxide (CO₂)] on this nocturnal activity pattern is studied in laboratory‐reared A. gambiae s.s. M molecular form. Sixteen mated females (5–10 days old) are held in individual chambers (diameter 3.5 cm, length 4.5 cm) in a wind‐tunnel with a continuous flow (8.0 cm s^?1) of clean air. At the onset of hours 3, 6 and 10 of the scotophase, their behaviour is recorded on video for 15 min in clean moving air and then for the next 15 min, with a specific treatment present in the clean airstream: (i) constant CO₂ (4.8%) plus human odour; (ii) pulsed CO₂ (5 s of every 30 s) plus human odour or (iii) control (clean air). Activities of individual mosquitoes are scored by direct observation of the video records for the incidents of ‘resting’, ‘walking’, ‘jumping’ and ‘flying’ in each of the 15‐min observation periods. There is a significant interaction between hour and treatment on mean changes in female activity level (P = 0.00004). Constant treatment increases the level of activity of A. gambiae females significantly, although only in hour 3 of the scotophase (P < 0.01), whereas pulsed and control treatments show no significant effect throughout the scotophase. Patterns of spontaneous activity in individual A. gambiae females thus appear to be modulated by host‐associated cues, resulting in a more active phase early in the night than might be expected from records of spontaneous activity under constant environmental conditions. Possible ecological and experimental implications of such an increase in activity are discussed in relation to host‐seeking behaviour.     

LiGAPS-Beef,a mechanistic model to explore potential and feed-limited beef production 2: sensitivity analysis and evaluation of sub-models

The model LiGAPS-Beef (Livestock simulator for Generic analysis of Animal Production Systems – Beef cattle) has been developed to assess potential and feed-limited growth and production of beef cattle in different areas of the world and to identify the processes responsible for the yield gap. Sensitivity analysis and evaluation of model results with experimental data are important steps after model development. The first aim of this paper, therefore, is to identify which parameters affect the output of LiGAPS-Beef most by conducting sensitivity analyses. The second aim is to evaluate the accuracy of the thermoregulation sub-model and the feed intake and digestion sub-model with experimental data. Sensitivity analysis was conducted using a one-at-a-time approach. The upper critical temperature (UCT) simulated with the thermoregulation sub-model was most affected by the body core temperature and parameters affecting latent heat release from the skin. The lower critical temperature (LCT) and UCT were considerably affected by weather variables, especially ambient temperature and wind speed. Sensitivity analysis for the feed intake and digestion sub-model showed that the digested protein per kg feed intake was affected to a larger extent than the metabolisable energy (ME) content. Sensitivity analysis for LiGAPS-Beef was conducted for ¾ Brahman×¼ Shorthorn cattle in Australia and Hereford cattle in Uruguay. Body core temperature, conversion of digestible energy to ME, net energy requirements for maintenance, and several parameters associated with heat release affected feed efficiency at the herd level most. Sensitivity analyses have contributed, therefore, to insight which parameters are to be investigated in more detail when applying LiGAPS-Beef. Model evaluation was conducted by comparing model simulations with independent data from experiments. Measured heat production in experiments corresponded fairly well to the heat production simulated with the thermoregulation sub-model. Measured ME contents from two data sets corresponded well to the ME contents simulated with the feed intake and digestion sub-model. The relative mean absolute errors were 9.3% and 6.4% of the measured ME contents for the two data sets. In conclusion, model evaluation indicates the thermoregulation sub-model can deal with a wide range of weather conditions, and the feed intake and digestion sub-model with a variety of feeds, which corresponds to the aim of LiGAPS-Beef to simulate cattle in different beef production systems across the world.     

Stimulation of physiological functions in cooled rats without rewarming after introducing ethylenediaminetetraacetate into lateral ventricles of the brain

On cooling the animals to the rectum temperature from approximately 37 to 24-28 degrees C the decreases were shown to occur in the frequency and amplitude of respiration motions, in the intensity of muscle electrical activity (thermoregulation muscle tone and cold muscle shivering), in the frequency of heart contractions. In 3-8 min after introducing ethylenediaminetetraacetate into a lateral ventricle of the rat brain the frequency and the amplitude of respiration motions increased statistically reliable and so did the intensity of thermoregulation muscle tone and cold muscle shivering (judging from the total muscle electrical activity). The doses of EDTA, which caused this effect, were by a factor of 30 - 100 less than the doses, which caused a similar stimulation of the functions in cooled animals after introduction into the blood.     

Circadian thermoregulation in suckling rabbit pups

The rabbit pup is well suited to track the age-dependent development of periodic thermoregulation during the suckling period. Since the litters are regularly nursed once per day for a total of 3 to 4 min, an exogenous, metabolic, nonphotic periodic variable is supposed to have an impact on the 24-h rhythm of body temperature. The authors monitored the course of core body temperature during the suckling period of 20 pups by means of a transmitter implanted intraperitoneally on day 3 postpartum. The 24-h mean rose from an average of 37.8+/-0.3 degrees C on day 4 of life to 39.5+/-0.2 degrees C at weaning on day 27, for 2 out of 20 pups, and day 28, for 18 out of 20 pups. In constant dim illumination, the pups exhibited a 24-h rhythm even on postnatal day 4, which consolidated around days 5 to 7. The rhythm consisted of a significant anticipatory rise of 0.4 to 0.6 degrees C above the respective 24-h mean commencing 2.5 to 3.5 h prior to nursing. Milk intake was followed by a further increase of temperature for an additional 0.3 to 0.6 degrees C. Then the temperature dropped for 1.2 to 1.5 degrees C within 1 to 3 h and returned to average 3 to 5 h later. During a 48-h fast, the rhythm continued to exist, though in a modified shape: the anticipatory component persisted almost unchanged; a further elevation of temperature, however, did not occur. Thus, the anticipatory component apparently is generated endogenously and the second surge represents an exogenous suckling-induced, thermogenic peak. When maternal nursing was advanced for 15 min/day for a total of 5 h, the temperature rhythm of the pups followed the shift of the zeitgeber in parallel. These data confirm the assumption that a circadian rhythm exists during the first postnatal days of the rabbit and that this rhythm is entrained by the 24-h nursing rhythm. The authors suggest that the biological significance of a feeding entrainable oscillator (FEO) in the rabbit might be to activate the pups prior to the periodic nursing visit of the rabbit doe. Thus, the pups are prepared to quantitatively use the one and only short nursing episode per day for maximal milk ingestion.     

黄瓜苗期耐低温性及相关生理指标遗传分析

选取耐低温弱光性不同的6份黄瓜材料9504、9507、9506、9517、9511、9514按Griffing方法Ⅱ配制完全双列杂交组合,对亲本及F1进行低温弱光处理(昼/夜温度12℃/8℃,每天光照7.5 h,光照强度30μmol·m-2·s-1)14 d后调查幼苗耐低温性、保护酶(POD和SOD)活性、渗透调节物质(可溶性蛋白质和脯氨酸)含量等生理指标,分析其遗传规律.结果显示,黄瓜亲本9504、9507及其组合F1幼苗的耐寒性较强,保护酶活性和脯氨酸含量较高,黄瓜幼苗耐寒性与其保护酶活性和渗透调节物质含量关系密切;黄瓜幼苗耐低温性、POD和SOD活性、可溶性蛋白质和脯氨酸含量所有性状的遗传符合加性-显性模型,它们的广义遗传力分别达82.133%、93.351%、97.368%、59.230%、93.460%,狭义遗传力达73.170%、53.191%、26.316%、58.587%、45.963%.研究表明,黄瓜耐低温性、POD和SOD活性、脯氨酸含量适于早代选择;幼苗可溶性蛋白质含量受生长环境的影响较大,可晚代选择.     

The effects of MIF-I, beta-endorphin and alpha-MSH on d-amphetamine induced paradoxical behavioral thermoregulation: possible involvement of the dopaminergic system

The neuropharmacological basis for d-amphetamine induced paradoxical behavioral thermoregulation remains unclear. This study examined thermoregulatory behavior of rats in a runway device that housed a heat source at one end and in which locomotion along the length of the runway could be observed. Sprague Dawley rats were pretreated with IP injections of saline, beta-endorphin, MIF-1, or alpha-MSH, with a repeat injection after 30 min. In a second experiment, d-amphetamine was administered as the repeat drug for all Ss. The results showed clear differences for heat-source-on vs. heat-source off. All peptides induced hypermotility, although no differentiated effects for the peptides on d-amphetamine induced paradoxical behavioral thermoregulation were found. These findings are discussed in light of the theoretical possibilities that: (a) a ceiling effect exists; (b) there are separate control systems for maintaining body temperature and another for behavioral thermoregulatory responses, and (c) other neurotransmitters may be involved in such induced paradoxical behavioral thermoregulation.     

Insulin resistance induced by hydrocortisone is increased in patients with abdominal obesity

Glucocorticoids hypersensitivity may be involved in the development of abdominal obesity and insulin resistance. Eight normal weight and eight obese women received on two occasions a 3-h intravenous infusion of saline or hydrocortisone (HC) (1.5 microg x kg(-1) x min(-1)). Plasma cortisol, insulin, and glucose levels were measured every 30 min from time(-30) (min) (time(-30)) to time(240). Free fatty acids, adiponectin, and plasminogen activator inhibitor-1 (PAI-1) levels were measured at time(-30), time(180), and time(240). At time(240), subjects underwent an insulin tolerance test to obtain an index of insulin sensitivity (K(ITT)). Mean(30-240) cortisol level was similar in control and obese women after saline (74 +/- 16 vs. 75 +/- 20 microg/l) and HC (235 +/- 17 vs. 245 +/- 47 microg/l). The effect of HC on mean(180-240) insulin, mean(180-240) insulin resistance obtained by homeostasis model assessment (HOMA-IR), and K(ITT) was significant in obese (11.4 +/- 2.0 vs. 8.2 +/- 1.3 mU/l, P < 0.05; 2.37 +/- 0.5 vs. 1.64 +/- 0.3, P < 0.05; 2.81 +/- 0.9 vs. 3.32 +/- 1.02%/min, P < 0.05) but not in control women (3.9 +/- 0.6 vs. 2.8 +/- 0.5 mU/l; 0.78 +/- 0.1 vs. 0.49 +/- 0.1; 4.36 +/- 1.1 vs. 4.37 +/- 1.2%/min). In the whole population, the quantity of visceral fat, estimated by computerized tomography scan, was correlated with the increment of plasma insulin and HOMA-IR during HC infusion [Delta mean(30-240) insulin (r = 0.61, P < 0.05), Delta mean(30-240) HOMA-IR (r = 0.66, P < 0.01)]. The increase of PAI-1 between time(180) and time(240) after HC was higher in obese women (+25%) than in controls (+12%) (P < 0.05), whereas no differential effect between groups was observed for free fatty acids or adiponectin. A moderate hypercortisolism, equivalent to that induced by a mild stress, has more pronounced consequences on insulin sensitivity in abdominally obese women than in controls. These deleterious effects are correlated with the amount of visceral fat.     

Effects of acute hyperinsulinemia on insulin signal transduction and glucose transporters in ovine fetal skeletal muscle

To test the effects of acute fetal hyperinsulinemia on the pattern and time course of insulin signaling in ovine fetal skeletal muscle, we measured selected signal transduction proteins in the mitogenic, protein synthetic, and metabolic pathways in the skeletal muscle of normally growing fetal sheep in utero. In experiment 1, 4-h hyperinsulinemic-euglycemic clamps were conducted in anesthetized twin fetuses to produce selective fetal hyperinsulinemia-euglycemia in one twin and euinsulinemia-euglycemia in the other. Serial skeletal muscle biopsies were taken from each fetus during the clamp and assayed by Western blot for selected insulin signal transduction proteins. Tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1, and the p85 subunit of phosphatidylinositol 3-kinase doubled at 30 min and gradually returned to control values by 240 min. Phosphorylation of extracellular signal-regulated kinase 1,2 was increased fivefold through 120 min of insulin infusion and decreased to control concentration by 240 min. Protein kinase B phosphorylation doubled at 30 min and remained elevated throughout the study. Phosphorylation of p70 S6K increased fourfold at 30, 60, and 120 min. In the second experiment, a separate group of nonanesthetized singleton fetuses was clamped to intermediate and high hyperinsulinemic-euglycemic conditions for 1 h. GLUT4 increased fourfold in the plasma membrane at 1 h, and hindlimb glucose uptake increased significantly at the higher insulin concentration. These data demonstrate that an acute increase in fetal plasma insulin concentration stimulates a unique pattern of insulin signal transduction proteins in intact skeletal muscle, thereby increasing pathways for mRNA translation, glucose transport, and cell growth.