bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for a functional renin-angiotensin system in full-term fetoplacental unit
Authors: Wilkes B. M. , Krim E. , Mento P. F.
Published: December 2017

This investigation was performed to study the renin-angiotensin system in the human fetoplacental circulation. Full-term placentas from uncomplicated pregnancies were studied within 30 min of delivery. The umbilical artery and vein to a single placental cotyledon were cannulated and the artery perfused with RPMI media (0.764 ml/min). Angiotensin II caused a dose-dependent increase in perfusion pressure that was blunted by the administration of the competitive angiotensin II receptor antagonist saralasin. The properties of human placental angiotensin II receptors were further defined in binding studies performed on a crude membrane fraction of placental cotyledons. In experiments performed at 22 degrees C, saturable binding reached steady state at 30 min and was linear with protein concentration. Scatchard analysis of binding data indicated a single class of high-affinity binding sites. The potency order to competitive binding of analogues and antagonists of angiotensin II was [Ile5]angiotensin II = [Sar1, Ala8]-angiotensin II greater than [Val5]angiotensin II greater than angiotensin III greater than angiotensin II-(3-8) hexapeptide. Further evidence for the physiological significance of angiotensin II binding sites was provided by measurements of the circulating components of the renin-angiotensin system in umbilical venous blood (n = 7). Plasma renin activity, angiotensin I, angiotensin-converting enzyme activity, angiotensin II, and aldosterone were each present in elevated amounts. These experiments provide evidence for an active renin-angiotensin system in the human fetal circulation that may modulate placental perfusion and function under physiological conditions.
Hepatic triglyceride hydrolysis and development of ketogenesis in rabbits
Authors: Duee P. H. , Pegorier J. P. , el Manoubi L. , Herbin C. , Kohl C. , Girard J.
Published: December 2017

Ketogenesis from endogenous fatty acids or exogenous oleate plus carnitine has been studied in isolated hepatocytes from fetal, newborn, and 70-day-old rabbits. During the first 48 h after birth, hepatic triacylglycerol stores decrease by 80%. The hydrolysis of hepatic triacylglycerol stores has been studied in isolated hepatocytes from 24-h-old fasting rabbits by using lysosomal acid lipase inhibitors and lysosomotropic agents. Their addition decreases the rates of ketone body production by 60-70%, suggesting that hepatic triacylglycerol hydrolysis proceeds via an acid lipase located in the lysosomes. Whereas the rates of ketogenesis from endogenous or exogenous fatty acids are very low in isolated hepatocytes from fetal rabbit, an eightfold increase in the rate of ketogenesis occurs between 6 and 24 h after birth; furthermore the hydrolysis of triacylglycerol stores is sufficient to support the ketogenic capacity in the hepatocytes isolated from 24-h-old rabbits. The emergence of ketogenesis in newborn rabbit hepatocytes is triggered by birth-associated factors rather than to an accurate stage of fetal maturation. Fatty acids are mainly oxidized in the mitochondria because peroxisomal oxidation does not exceed 10-15% of the overall beta-oxidation. Isolated hepatocytes incubated with [1-14C]oleate exhibit at birth a preferential channeling of fatty acid into esterification (93% of oleate metabolized) rather than into oxidation. Conversely oleate oxidation represents 50% of total oleate metabolized 24 h after birth. Factors involved in this switch on of the partition of oleate into esterification and oxidation during the 1st day after birth are discussed.
Glucose turnover and oxidation are increased in the iron-deficient anemic rat
Authors: Henderson S. A. , Dallman P. R. , Brooks G. A.
Published: December 2017

To test the hypothesis that glucose metabolism is altered by iron deficiency, rates of glucose turnover and oxidation were assessed concurrently with the metabolic rate (VO2) in iron-deficient anemic rats and in normal rats at rest. Male Sprague-Dawley rats, 21 days old, were fed a diet containing either 6 mg iron/kg feed (iron-deficient group) or 50 mg iron/kg feed (iron-sufficient control group) for 3-4 wk. After dietary treatment the iron-deficient group was anemic, with hemoglobin levels of 5.8 +/- 0.2 g/dl, compared with 13.8 +/- 0.4 g/dl for controls. To study glucose metabolism, rats received a 90 min primed-continuous infusion of [6-3H]-and [U-14C]glucose via an indwelling jugular catheter. Serial blood samples were removed from a carotid catheter for determination of glucose concentration and specific activity. Expired air was monitored for VO2, VCO2, and 14CO2. The VO2 (ml X kg-1 X min-1) of iron-deficient rats was 20% higher than controls. Iron-deficient rats had a greater rate of glucose turnover (94 +/- 4 vs. 52 +/- 3 mumol X kg-1 X min-1) and a greater glucose recycling rate, even when normalized to VO2. Despite a higher blood glucose concentration (5.5 +/- 0.6 vs. 4.1 +/- 0.1 mM), the metabolic clearance rate was greater in iron-deficient animals (18 +/- 1 vs. 13 +/- 1 ml X kg-1 X min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Response of ketone body metabolism to exercise during transition from postabsorptive to fasted state
Authors: Fery F. , Balasse E. O.
Published: December 2017

This study examines the effects of a 2-h exercise of moderate intensity (50% of VO2 max) on the tracer-determined turnover rate of ketone bodies (KB) in 21 normal subjects fasted for 16 h, 5 days, whose basal ketonemia ranged between 0.09 and 6.16 mM. The KB response observed at the end of exercise is a function of the initial degree of ketosis. When basal ketonemia is below 0.6 mM, exercise enhances ketogenesis (Ra), the amplitude of this process being positively correlated with KB level. There is a concomitant acceleration of the metabolic clearance rate (MCR) of KB attaining 40-50%. When ketonemia exceeds 2.5 mM, the stimulatory effects of exercise on Ra and on MCR become less marked as basal ketonemia rises and are completely abolished or even reversed when initial KB level is higher than 3-4 mM. The pattern of changes in the concentration and in the overall disposal rate of KB were similar to that of Ra. It is suggested that the parallel inhibition of the stimulatory effect of work on hepatic ketogenesis and on muscular extraction of ketones associated with increasing degrees of fasting hyperketonemia has two physiological implications: it maintains the preferential utilization of KB by nonmuscular tissues (presumably the brain) and prevents the development of uncontrolled hyperketonemia, despite the intense catabolic situation created by the combination of exercise and starvation.
Hormones in perinatal rat and spiny mouse: relation to altricial and precocial timing of birth
Authors: Lamers W. H. , Mooren P. G. , Griep H. , Endert E. , Degenhart H. J. , Charles R.
Published: December 2017

Rat (Rattus norvegicus) and spiny mouse (Acomys cahirinus) are closely related murine species that, due to their altricial (rat) and precocial (spiny mouse) modes of development, differ in the developmental timing of birth. A comparison between the developmental profiles of plasma glucagon, insulin, thyroxine, triiodothyronine, and glucocorticosteroid hormone was carried out to elucidate the question to what extent these hormonal profiles were related to the timing of birth. Although corticosterone is the major circulating glucocorticosteroid in rat, only cortisol was found in the spiny mouse. The onset of increases in glucocorticosteroid and thyroid hormone levels occurred at the same developmental time points in both species. A neonatal increase in triiodothyronine levels was observed in the spiny mouse only. In both species the immediate perinatal period was characterized by decreases in the ratio of insulin and glucagon levels and the level of glucocorticosteroids. The observed developmental patterns of hormonal levels were found to be consistent with the observed developmental pattern of enzymic maturation in the respiratory and gastrointestinal tract, which play a critical role in the adaptation to the extrauterine environment.
Effect of gestational hyperglycemia on insulin secretion in vivo and in vitro by fetal rat pancreas
Authors: Bihoreau M. T. , Ktorza A. , Kervran A. , Picon L.
Published: December 2017

The effects of gestational hyperglycemia on B-cell function were studied in near-term fetuses from unrestrained pregnant rats made slightly or highly hyperglycemic using continuous glucose infusion during the last week of pregnancy. Pancreatic and plasma insulin and insulin secretion in vitro were studied in the fetuses. Compared with controls, slightly hyperglycemic fetuses showed increased pancreatic and plasma insulin concentrations and similar insulin release in response to glucose in vitro. In highly hyperglycemic fetuses, pancreatic and plasma insulin concentrations were unchanged compared with controls, and insulin release in vitro was insensitive to glucose and to the mixture glucose plus theophylline. These results confirm that glucose is able to stimulate insulin secretion in normal or slightly hyperglycemic fetuses and suggest that severe hyperglycemia per se, without association of other metabolic disorders or toxic injuries, profoundly alters the stimulus-secretion coupling of the fetal rat B-cell.
Physiological factors affecting secretion of parotid hormone
Authors: Leonora J. , Tieche J. M. , Celestin J.
Published: December 2017

A parotid hormone (PH) that stimulates a dentinal fluid transport (DFT) mechanism in rat teeth is part of the hypothalamic parotid gland endocrine axis (HPEA). Infusion of a porcine hypothalamus-thalamic tissue extract (PHTE) into anesthetized rats stimulates the DFT mechanism in intact animals but is ineffective in parotidectomized rats. Infusion of PHTE into intact conscious pigs raises the plasma titer of immunoreactive PH (iPH) five- to eightfold. Parotidectomy prevents the response. The feeding of pig chow is a potent stimulus for iPH secretion: an 11-fold increase is reached within 10-20 min, and the response is directly related to the length of the feeding stimulus. No response is obtained after parotidectomy. The secretion of saliva and iPH from the parotids occurs independently of each other, suggesting different control mechanisms for each function. The immediate secretion of iPH in response to feeding and its relationship to DFT stimulation may represent a systemic physiological process by which resistance of teeth to decay is enhanced at a time when the acidogenic potential of the oral microbes is maximum.
Effects of insulin and epinephrine on Na+-K+ and glucose transport in soleus muscle
Authors: Clausen T. , Flatman J. A.
Published: December 2017

To identify possible cause-effect relationships between changes in active Na+-K+ transport, resting membrane potential, and glucose transport, the effects of insulin and epinephrine were compared in rat soleus muscle. Epinephrine, which produced twice as large a hyperpolarization as insulin, induced only a modest increase in sugar transport. Ouabain, at a concentration (10(-3) M) sufficient to block active Na+-K+ transport and the hyperpolarization induced by the two hormones, did not interfere with sugar transport stimulation. After Na+ loading in K+-free buffer, the return to K+-containing standard buffer caused marked stimulation of active Na+-K+ transport, twice the hyperpolarization produced by insulin but no change in sugar transport. The insulin-induced activation of the Na+-K+ pump leads to decreased intracellular Na+ concentration and hyperpolarization, but none of these events can account for the concomitant activation of the glucose transport system. The stimulating effect of insulin on active Na+-K+ transport was not suppressed by amiloride, indicating that in intact skeletal muscle it is not elicited by a primary increase in Na+ influx via the Na+/H+-exchange system.
Effects of CRF and ANG II on ACTH and vasopressin release in conscious dogs
Authors: Klingbeil C. K. , Keil L. C. , Chang D. , Reid I. A.
Published: December 2017

The aim of the present study was to examine the effects of corticotropin-releasing factor (CRF) in conscious dogs and to determine whether the stimulation of adrenocorticotropic hormone (ACTH) release by angiotensin II (ANG II) results from potentiation of the action of CRF. In addition, the possible role of CRF in the stimulation of vasopressin released by ANG II was investigated. The following experiments were performed: 1) intravenous saline infusion; 2) ANG II (10 ng.kg-1.min-1) alone; 3) vasopressin (1 ng.kg-1.min-1) alone; 4) CRF (0.001, 0.01, or 0.1 microgram/kg iv) bolus; 5) vasopressin (1 ng.kg-1.min-1) and CRF (0.1 microgram/kg) together; 6) CRF (0.001, 0.01, or 0.1 microgram/kg) and ANG II (10 ng.kg-1.min-1) together; 7) ANG II (10 ng.kg-1.min-1) followed 15 min later with CRF (0.001, 0.01, or 0.1 microgram/kg). Each dose of CRF was tested on a different day. Infusion of ANG II alone stimulated the release of ACTH, cortisol, and vasopressin. Administration of CRF produced dose-dependent increases in plasma ACTH and cortisol concentrations, and the highest dose of CRF increased plasma vasopressin concentration. CRF given together with ANG II did not potentiate the stimulation of ACTH release by CRF. Vasopressin at the dose tested did not stimulate ACTH release but potentiated the ACTH response to CRF. ANG II stimulated vasopressin release but did not potentiate the AVP response to CRF. These results show that, in conscious dogs, ANG II and CRF each increase plasma ACTH concentration and that the ACTH response to CRF is potentiated by vasopressin but not by ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of thyroid hormones on oxidative and nonoxidative glucose metabolism in humans
Authors: Muller M. J. , Acheson K. J. , Jequier E. , Burger A. G.
Published: December 2017

The glucoregulatory function of thyroid hormones was investigated in six healthy subjects before and after 14 day 3,5,3',5'-tetraiodothyronine (T4) treatment (300 micrograms/day) using a sequential clamp protocol for 5 h at euglycemia (0–2 h) and hyperglycemia (165 mg/dl, 2–5 h) and different insulin infusion rates (1.0 for 0–3.5 h and 6.5 mU.kg-1.min-1, for 3.5–5 h). T4 treatment increased basal energy expenditure (+8%), glucose disposal (+31%), and oxidation (+87%) but decreased nonoxidative glucose metabolism (-30%) and was without effect on lipid oxidation. During the euglycemic clamp, T4 treatment enhanced insulin-induced glucose disposal (+16%), glucose oxidation (+34%), and inhibition of lipid oxidation (-66 vs. -40%); nonoxidative glucose metabolism was stimulated to a similar extent before and after T4. During hyperglycemia, 3,5,3'-triiodothyronine (T3) did not affect glucose disposal but increased carbohydrate-induced lipogenesis at both insulin infusion rates. We conclude that T4 treatment promotes glucose disposal and oxidation, T3 decreases noninsulin-mediated glucose storage but does not antagonize insulin action.
Effects of glucose and insulin on fetal glucose oxidation and oxygen consumption
Authors: Hay W. W. , DiGiacomo J. E. , Meznarich H. K. , Hirst K. , Zerbe G.
Published: December 2017

Glucose and insulin clamp experiments were performed in late-gestation fetal lambs to quantify the separate and combined effects of physiological concentrations of fetal glucose (G; 7.3-62.6 mg/dl) and insulin (I; 2-119 uU/ml) on fetal glucose metabolism and O2 consumption. Fetal glucose utilization rate (GUR) varied from 2.82 to 15.12 mg.min-1.kg-1. Fetal CO2 production from fetal glucose carbon oxidation (CO2Pr) varied from 32 to 234 mumol.min-1.kg-1 and was directly related to G and I [CO2Pr = -0.00868 + 0.00578 (G) + 0.000901 (I) - 0.0000619 (G)2, r = 0.88] and to GUR (CO2Pr = 0.0159 GUR - 0.0130, r = 0.89). CO2Pr accounted for 54.7% of the mean GUR and for 35.9% of the mean umbilical O2 uptake (UO2U), ranging from 26.0% in the control studies to 36.5% in hyperinsulinemic-euglycemic studies and to 45.1% in hyperinsulinemic-hyperglycemic studies. UO2U varied from 0.200 to I [UO2U = 0.303 + [0.000813 (G)] + [0.0000461 (I)], r = 0.89] and to GUR (UO2U = 0.0098 GUR + 0.275, r = 0.91). These results define independent (additive) effects of G and I on glucose oxidation in the late gestation fetal lamb and demonstrate the necessity for considering the levels of both G and I when studying these aspects of fetal metabolism.
Role of triglyceride-fatty acid cycle in controlling fat metabolism in humans during and after exercise
Authors: Wolfe R. R. , Klein S. , Carraro F. , Weber J. M.
Published: December 2017

We have investigated the role of triglyceride-fatty acid cycling in amplifying control of the net flux of fatty acids in response to exercise and in recovery from exercise. Five normal volunteers were infused with [1-13C]palmitate and D-5-glycerol throughout rest, 4 h of treadmill exercise at 40% maximum O2 consumption, and 2 h of recovery. Total fat oxidation was quantified by indirect calorimetry. Lipolysis (rate of appearance of glycerol) increased from 2.1 +/- 0.3 to 6.0 +/- 1.2 mumol.kg-1.min-1 after 30 min of exercise and progressively increased thereafter to a value of 10.5 +/- 0.8 mumol.kg-1.min-1 after 4 h. Lipolysis decreased rapidly during the first 20 min of recovery, but it was still significantly elevated after 2 h of recovery. The rate of appearance of free fatty acids followed the same pattern of response. Seventy percent of released fatty acids were reesterified at rest, and this value decreased to 25% within the first 30 min of exercise. Reesterification remained less than 35% of lipolysis until the start of recovery, at which time the value rose to 90%. In exercise, more than one-half the increase in fat oxidation could be attributed to the reduction in the percent reesterification. Most of the change in percent reesterification during exercise and recovery was caused by changes in extracellular cycling of fatty acids released into plasma. We conclude that triglyceride-fatty acid cycling plays an important role in enabling a rapid response of fatty acid metabolism to major changes in energy metabolism.
Chemical and elemental analysis of humans in vivo using improved body composition models
Authors: Heymsfield S. B. , Waki M. , Kehayias J. , Lichtman S. , Dilmanian F. A. , Kamen Y. , Wang J. , Pierson R. N.
Published: December 2017

Six chemical compartments [water, protein, mineral (osseus and cellular), glycogen, and fat] consisting of 11 elements (N, C, Ca, Na, Cl, K, H, P, O, S, and Mg) comprise greater than or equal to 99% of body weight in living humans. The combination of three neutron-activation systems, whole body 40K counting, and 3H2O dilution at Brookhaven National Laboratory now potentially makes it possible to quantify greater than or equal to 96% of the chemical and elemental determinants of body weight in vivo. The aims of the present study were 1) to develop 6- and 11-compartment chemical and elemental models, respectively, and 2) to evaluate these models in a group of 20 healthy adults. Results demonstrated that body weight estimated from either chemical or elemental components was highly correlated with (both r = 0.97, P less than 0.001) and on average differed by less than 4% from actual body weight. The compartmental results obtained using the chemical model were also evaluated by comparing calculated and actual body density (Db) estimated by underwater weighing. Calculated Db [1.041 +/- 0.017 (SD) g/ml] agreed closely and was highly correlated with actual Db (1.039 +/- 0.018 g/ml; r = 0.82; P less than 0.001). Hence a near-complete chemical and elemental analysis of living human subjects is now possible and, with potential future refinements, represents an important opportunity to quantify the effects of gender, aging, and ethnic status on body composition.
Energy expenditure by doubly labeled water: validation in lean and obese subjects
Authors: Ravussin E. , Harper I. T. , Rising R. , Bogardus C.
Published: December 2017

The doubly labeled water (2H2(18)O) method to assess energy expenditure in free-living conditions has been successfully validated against gas exchange measurements in lean healthy volunteers in both sedentary conditions and during sustained heavy exercise. However, no data are available on obese subjects. We therefore compared the 2H2(18)O method with indirect calorimetry (respiratory chamber) in 12 male subjects covering a wide range of body weight and composition (61-190 kg, 7-41% fat). Isotope pool sizes and elimination rates were calculated from 18O and 2H enrichments in baseline urine samples and in 7-h, 11.5-h, and daily postdose urine samples using the multipoint slope/intercept method. Results were corrected for isotopic fractionation. Mean 7-day energy expenditure in the respiratory chamber varied from 1,851 to 4,105 kcal/day. The doubly labeled water method tended to underestimate energy expenditure (-2.5 +/- 5.8%, not equal to 0, range -14 to +4%), with the larger underestimate observed in heavier and fatter subjects (r = -0.82 and -0.68, P less than 0.02, respectively). The underestimation in heavier subjects might be related to larger sequestration of deuterium during fat synthesis. In conclusion, the doubly labeled water method is a suitable and accurate method to measure energy expenditure in free-living conditions but might provide a slightly underestimated figure in fatter subjects.
Glucose transporter number, activity, and isoform content in plasma membranes of red and white skeletal muscle
Authors: Goodyear L. J. , Hirshman M. F. , Smith R. J. , Horton E. S.
Published: December 2017

The fiber type composition of a skeletal muscle is an important determinant of its ability to take up glucose. Although numerous factors may account for this phenomenon, we have hypothesized that fiber type differences in glucose transporter number, isoform content, and/or intrinsic activity play an important role. Skeletal muscle plasma membranes were prepared from red and white gastrocnemius muscle from male Sprague-Dawley rats that were either exercised on a treadmill (1 h, 20 m/min, 10% grade), injected with 20 U insulin, or remained sedentary. In sedentary rats, plasma membrane glucose transporter number (cytochalasin B binding) was 2.4-fold greater in red compared with white muscle. Exercise and insulin both increased glucose transporter number by 40% in red muscle and twofold in white muscle. Maximal velocity of glucose transport (Vmax) was 2-fold greater in red compared with white muscle, whereas exercise and insulin increased Vmax by 2.3-fold in red muscle and 3.6-fold in white muscle. Glucose transporter turnover number, a measure of the average intrinsic activity of transporters in the plasma membrane, was not different between red and white muscle and increased 80–90% with exercise and insulin in both red and white muscle. Both GLUT-1 and GLUT-4 isoform content were greater in red than white muscle. These results suggest that fiber type differences in rates of glucose uptake in resting, insulin-stimulated, and contraction-stimulated skeletal muscle may be due to differences in the number but not the intrinsic activity of glucose transporter proteins.
Thermogenesis and fructose metabolism in humans
Authors: Schwarz J. M. , Acheson K. J. , Tappy L. , Piolino V. , Muller M. J. , Felber J. P. , Jequier E.
Published: December 2017

Resting metabolic rate was measured in 10 healthy volunteers (25 yr, 73 kg, 182 cm) for 1 h before and 4 h during intravenous (iv) fructose administration (20% at 50 mumol.kg-1.min-1) with (+P) or without (-P) propranolol (100 micrograms/kg, 1 microgram.kg-1.min-1) during the last 2 h. Some subjects were studied a further 2 h with fructose infusion and +P or -P in hyperinsulinemic (2.9 pmol.kg-1.min-1) euglycemic conditions. Glucose turnover ([3-3H]glucose, 20 muCi bolus and 0.2 muCi/min) was calculated over 30 min at 0, 2, 4, and 6 h. The thermic effect of iv fructose was approximately 7.5% and decreased to 4.9 +/- 0.4% (P less than 0.01) +P. During the euglycemic clamp the thermic effect was 6.2 +/- 0.9% (-P) and 5.3 +/- 0.9% (+P). Hepatic glucose production (HGP) was 11.7 mumol.kg-1.min-1 (0 h) and did not change after 2 h iv fructose (11.8 +/- 0.5 and 9.8 +/- 0.6 mumol.kg-1.min-1 -P and +P, respectively) but increased to 13.8 +/- 0.9 (-P) and 12.9 +/- 0.8 mumol.kg-1.min-1 (+P) (P less than 0.01) after 4 h. HGP was suppressed to varying degrees during the euglycemic clamp. It is concluded that 1) the greater thermic effect of fructose compared with glucose is probably due to continued gluconeogenesis (which is suppressed by glucose or glucose-insulin) and the energy cost of fructose metabolism to glucose in the liver. 2) There is a sympathetically mediated component to the thermic effect of fructose (approximately 30%) that is not mediated by elevated plasma insulin concentrations similar to those observed with iv glucose.
Isotopomer spectral analysis of triglyceride fatty acid synthesis in 3T3-L1 cells
Authors: Kharroubi A. T. , Masterson T. M. , Aldaghlas T. A. , Kennedy K. A. , Kelleher J. K.
Published: December 2017

A new analysis of stable isotope data for biosynthesis reaction, isotopomer spectral analysis (ISA), is demonstrated. ISA is theoretically applicable for polymerization biosynthesis where data are collected using selected ion-monitoring gas chromatography-mass spectrometry. ISA utilizes the discrete spectrum of isotopomer abundances and the multinomial distribution to estimate two key parameters related to the biosynthesis. These parameters are 1) the dilution of the precursor immediately before biosynthesis and 2) the dilution of the newly synthesized product in the sampled compartment. Differentiated 3T3-L1 cells incorporated 2 mM [1,2-13C]acetate into triglyceride palmitate, yielding a spectrum of mass isotopomers of palmitate. The set of equations for the first nine isotopomers were solved for the two parameters using nonlinear regression. We found that precursor dilutions for acetate and glucose were constant over time, whereas the product dilution parameter increased with time, as expected for cells accumulating triglyceride palmitate. Mathematical procedures are presented for calculating 1) the predicted isotopomer fractional abundance values and 2) the correction for atoms other than the tracer atom in the mass ion.
Measurement of bicarbonate turnover in humans: applicability to estimation of energy expenditure
Authors: Elia M. , Fuller N. J. , Murgatroyd P. R.
Published: December 2017

Bicarbonate turnover and energy expenditure were assessed in six healthy male volunteers, by the use of a constant infusion of radiolabeled bicarbonate (NaH14CO3) administered over 36 h, while the volunteers were confined to a whole body indirect calorimeter. Recovery and dilution of isotope were assessed from measurements made on continuous collections of CO2, entering and leaving the calorimeter, urine, and intermittent spot breath and saliva samples. Mean recovery of infused label in gaseous CO2 was 95.6 +/- 1.1% (SD) between 12 and 36 h. Applying a 95% mean recovery of label to each subject individually enabled the use of integrated mean specific activity of CO2 in spot breath and urine samples to predict measured net CO2 production and energy expenditure to within about +/- 6%. Estimates based on urinary measurements were compromised slightly by the exchange of label through the bladder wall (this was dependent on pH and volume of urine). It is concluded that this constant-infusion labeled bicarbonate method offers a potentially useful means of assessing net CO2 production and total energy expenditure over the short term (e.g., 1-3 days).
Carbohydrate metabolism during pregnancy in control subjects and women with gestational diabetes
Authors: Catalano P. M. , Tyzbir E. D. , Wolfe R. R. , Calles J. , Roman N. M. , Amini S. B. , Sims E. A.
Published: December 2017

The purpose of this study was to characterize carbohydrate metabolism associated with the development of gestational diabetes. Six control (Ctl) and ten women with gestational diabetes mellitus (GDM) were evaluated using an intravenous glucose tolerance test and hyperinsulinemic-euglycemic clamp with [6,6-2H2]glucose prior to conception (P) and at 12-14 (E), and 34-36 wk of gestation (L). There was an increase (P = 0.0001) in first-phase insulin response in Ctl (P 174 +/- 133, E 388 +/- 120, and L 587 +/- 303 microU/ml) and GDM (P 197 +/- 94, E 267 +/- 77, and L 376 +/- 162 microU/ml) but a significant (P = 0.02) lag in change in GDM with advancing gestation. Basal endogenous glucose production increased during gestation [Ctl: P 2.74 +/- 0.23, E 2.62 +/- 0.38, and L 3.14 +/- 0.36; GDM: P 2.68 +/- 0.51, E 2.78 +/- 0.45, and L 2.98 +/- 0.48 mg.kg fat-free mass (FFM)-1 x min-1; P = 0.02], but there was resistance to suppression by insulin infusion (P = 0.03) in late gestation (GDM: 0.61 +/- 0.44 vs. Ctl: 0.16 +/- 0.17 mg.kg FFM-1 x min-1). Insulin sensitivity decreased during gestation (Ctl: P 10.78 +/- 2.78, E 8.34 +/- 2.36, and L 4.75 +/- 1.22; GDM: P 7.49 +/- 2.13, E 7.40 +/- 1.45, and L 4.21 +/- 1.01 mg.kg FFM-1 x min-1; P = 0.0001) and was primarily decreased (P = 0.04) in GDM compared with Ctl from P through E. These findings closely resemble those of non-insulin-dependent, predominantly insulin-resistant diabetes, which is often a sequel of GDM.
Coexistence of beta 1-, beta 2-, and beta 3-adrenoceptors in dog fat cells and their differential activation by catecholamines
Authors: Galitzky J. , Reverte M. , Portillo M. , Carpene C. , Lafontan M. , Berlan M.
Published: December 2017

The existence of a beta 3-adrenoceptor (in addition to classical beta 1- and beta 2-), its involvement in the control of lipolysis and its recruitment by catecholamines were investigated in dog adipose tissue. Isoproterenol, norepinephrine, and the beta 2-selective agonist procaterol fully activated lipolysis in adipocytes (order of potency: isoproterenol > norepinephrine = procaterol). beta 3-Adrenergic agonists stimulated lipolysis with the order of potency: BRL 37344 > CGP 12177 > SR 58611A. Propranolol and bupranolol (nonselective beta-antagonists) antagonized, with a low potency, the effect of BRL 37344, whereas the beta 1-antagonist CGP 20712A and the beta 2-antagonist ICI 118551 were without action. CGP 20712A inhibited the effect of lower concentrations of agonists (0.05 microM isoproterenol, 0.1 microM norepinephrine and 0.1 microM procaterol) with an inhibitory constant (mean Ki) of 0.0075, 0.032 and > 10 microM, respectively. Mean Ki values for the beta 2-antagonist ICI 118551 were 1.744, 1.243, and 0.019 microM. This result indicates that low concentrations of isoproterenol and norepinephrine stimulate lipolysis mainly via beta 1-adrenoceptors in dog fat cells. Inversely, the lipolytic effect of higher concentrations of agonists i.e., 1 microM isoproterenol and catecholamines, was weakly antagonized by CGP 20712A or ICI 118551 while the nonselective beta-antagonists bupranolol and propranolol suppressed the effects with the order of potency expected for a beta 3-adrenoceptor: bupranolol > propranolol. These data indicate 1) the presence of a functional beta 3-adrenoceptor that coexists with beta 1- and beta 2-adrenoceptors in dog fat cells; 2) a separation of the differential potencies of physiological amines in the activation of lipolysis through beta 1-, beta 2-, and beta 3-adrenoceptors; the lipolytic response initiated at low concentrations (submicromolar range) of norepinephrine is primarily mediated by the beta 1-adrenoceptor subtype; and 3) an activation of the beta 3-adrenoceptor that occurs at higher concentrations of catecholamines.
Natriuretic peptide C-receptor: more than a clearance receptor
Authors: Levin E. R.
Published: December 2017

The natriuretic peptide family of proteins acts through two distinct classes of receptors that signal through entirely different mechanisms. The elucidation of the structure of the guanylate cyclase-containing receptor proteins has provided a better understanding of the mechanisms by which the natriuretic peptides regulate diverse functions of salt and water balance, in conjunction with other vasoactive peptides. A second receptor class was named for the originally described function of this protein to clear the natriuretic peptides from plasma. The mechanism of signaling for the natriuretic peptide clearance receptor is not firmly established. All known members of the natriuretic peptide family bind to, and can theoretically act through, the clearance receptor. This review summarizes the known features of the natriuretic peptide clearance receptor, a protein that contains extracellular and transmembrane domains and a short cytoplasmic segment. Recent studies have pointed to new and potentially important functions for this protein in mediating the actions of the natriuretic peptides.
Corticosterone inhibits uncoupling protein gene expression in brown adipose tissue
Authors: Moriscot A. , Rabelo R. , Bianco A. C.
Published: December 2017

Uncoupling protein (UCP) mRNA levels were studied in the interscapular brown adipose tissue (BAT) of rats undergoing different manipulations of the adrenal function and BAT adrenergic stimulation. Adrenalectomy did not affect UCP mRNA levels for up to 8 days post-surgery. However, adrenalectomized rats underwent a greater increase in UCP mRNA levels (26%) than intact rats after 4 h of cold exposure. Administration of corticosterone (500 micrograms.100 g body wt-1.day-1 sc) to intact or adrenalectomized rats, kept at 28 degrees C, produced a marked decrease of UCP mitochondrial content and cellular mRNA levels in a time-dependent manner (30% by 12 h and 50% by 24 h). Pretreatment of intact rats with corticosterone virtually abolished the UCP mRNA response to cold and norepinephrine (NE). In contrast, when rats had been preexposed to cold for 96 h, the injection of corticosterone did not affect UCP mRNA. These results show that corticosterone is a powerful inhibitor of UCP gene expression in vivo. Corticosterone inhibits both basal gene expression at thermoneutrality and the response to adrenergic stimulation either by cold or exogenous NE, suggesting a direct action on BAT. The data further suggest that corticosterone inhibits the initial accumulation of UCP mRNA mediated by UCP gene transcription, rather than accelerating the degradation of UCP mRNA.
Physiological role of galanin in the regulation of anterior pituitary function in humans
Authors: Giustina A. , Licini M. , Schettino M. , Doga M. , Pizzocolo G. , Negro-Vilar A.
Published: December 2017

The aim of our study was to elucidate the physiological role of the neuropeptide galanin in the regulation of anterior pituitary function in human subjects. Six healthy men (age range 26-35 yr, body mass index range 20-24 kg/m2) underwent in random order 1) an intravenous bolus injection of growth hormone-releasing hormone (GHRH)-(1-29)-NH2 (100 micrograms) + thyrotropin-releasing hormone (TRH, 200 micrograms) + luteinizing hormone-releasing hormone (LHRH, 100 micrograms) + corticotropin-releasing hormone (CRH, 100 micrograms), and 2) intravenous saline (100 ml) at time 0 plus either human galanin (500 micrograms) in saline (100 ml) or saline (100 ml) from -15 to +30 min. Human galanin determined a significant increase in serum GH (GH peak: 11.3 +/- 2.2 micrograms/l) from both baseline and placebo levels. No significant differences were observed between GH values after galanin and those after GHRH alone (24.3 +/- 5.2 micrograms/l). Human galanin significantly enhanced the GH response to GHRH (peak 49.5 +/- 10 micrograms/l) with respect to either GHRH or galanin alone. Human galanin caused a slight decrease in baseline serum adrenocorticotropic hormone (ACTH; 16.3 +/- 2.4 pg/ml) and cortisol levels (8 +/- 1.5 micrograms/dl). Galanin also determined a slight reduction in both the ACTH (peak 27 +/- 8 pg/ml) and cortisol (peak 13.8 +/- 1.3 micrograms/dl) responses to CRH. Baseline and releasing hormone-stimulated secretions of prolactin, thyroid-stimulating hormone, LH, and follicle-stimulating hormone were not altered by galanin. Our data suggest a physiological role for the neuropeptide galanin in the regulation of GH secretion in humans.(ABSTRACT TRUNCATED AT 250 WORDS)
Direct plasma radioimmunoassay for rat amylin-(1-37): concentrations with acquired and genetic obesity
Authors: Pieber T. R. , Roitelman J. , Lee Y. , Luskey K. L. , Stein D. T.
Published: December 2017

Amylin (islet-associated polypeptide) is a 37-amino acid peptide that is cosecreted with insulin from the pancreatic beta-cell. Accurate measurement of its plasma levels is important for delineating the physiological range over which amylin acts. We describe a reproducible, highly specific, and sensitive radioimmunoassay for direct measurement of plasma amylin-(1-37). We measured changes in portal and systemic plasma amylin and insulin in three groups of anesthetized rats: lean young adult and old adult Wistar rats with acquired obesity, and Wistar fatty [WDF/TaFa (fa/fa)] rats, a model of genetic obesity and insulin resistance derived from the Wistar strain. Changes in response to fasting, feeding, and intravenous stimulation with glucose plus arginine were assessed. We find that the amylin-to-insulin ratio is constant in fasted or fed young and old rats because of proportionate increases in both entities with aging. In genetically obese Wistar rats, amylin and insulin levels are three- to tenfold higher than in lean young or obese old normal controls. Islet stimulation by feeding or intravenous glucose plus arginine resulted in a decreased amylin-to-insulin molar ratio in all groups. When normalized for the degree of islet stimulation, amylin-to-insulin ratios were significantly elevated in genetically obese vs. normal rats, both in the portal and systemic circulation. These results demonstrate that aging-related weight gain in normal rats is associated with moderate and proportional increases in amylin and insulin, whereas genetic obesity is characterized by elevated amylin and an increased amylin-to-insulin ratio. Implications for the pathogenesis of insulin resistance and obesity are discussed.
Effect of antilipolysis on heart and skeletal muscle glucose uptake in overnight fasted humans
Authors: Nuutila P. , Knuuti M. J. , Raitakari M. , Ruotsalainen U. , Teras M. , Voipio-Pulkki L. M. , Haaparanta M. , Solin O. , Wegelius U. , Yki-Jarvinen H.
Published: December 2017

We quantitated how lowering of free fatty acid (FFA) by an antilipolytic agent (acipimox) in the fasting state changes glucose uptake in heart and skeletal muscles. Glucose uptake in these tissues was measured two times in seven normal subjects, once after acipimox and once after placebo, using positron emission tomography-derived [18F]fluoro-2-deoxy-D-glucose kinetics. Plasma glucose and insulin remained at their fasting concentrations in both studies. Fasting FFA concentrations were 60% lower after acipimox (238 +/- 39) than placebo (645 +/- 78 mumol/l, P < 0.001). Glucose uptake increased 6 +/- 2-fold in the heart by acipimox (344 +/- 49 vs. 108 +/- 40 mumol.kg muscle-1.min-1, P < 0.002) and 1.5-fold in arm muscles (27.7 +/- 2.6 vs. 18.6 +/- 1.2 mumol.kg muscle-1.min-1, P < 0.02). Heart (r = -0.93, P < 0.001) and arm (r = -0.82, P < 0.001) glucose uptakes were inversely related to serum FFA. We conclude that serum FFA are inversely related to glucose uptake in heart and arm skeletal muscles after an overnight fast. These data indicate that compensatory glycogenolysis, although it may occur, does not prevent operation of the glucose-FFA cycle under fasting conditions.
Cold exposure attenuates effects of secretagogues on serum prolactin and growth hormone levels in male rats
Authors: Rauhala P. , Idanpaan-Heikkila J. J. , Lang A. , Tuominen R. K. , Mannisto P. T.
Published: December 2017

The stimulatory effect of morphine, dexmedetomidine (an alpha 2-adrenoceptor agonist), 1-(3-chlorophenyl)-piperazine (m-CPP, a 5-HT1B agonist), U-50488H (a kappa-opioid receptor agonist), pimozide (a dopamine antagonist), and restraint stress on prolactin and growth hormone (GH) secretion was compared during cold exposure (4 degrees C) and under basal conditions (30 degrees C) in male rats. Rectal temperature was also measured. The stimulatory effect of morphine, dexmedetomidine, m-CPP, and partially U-50488H on prolactin secretion was attenuated in rats kept at 4 degrees C. Cold exposure did not abolish prolactin release induced by pimozide and restraint stress. Cold exposure also antagonized the effect of morphine and dexmedetomidine on GH secretion. The stimulatory effect of morphine on prolactin and GH secretion was restored in the warm environment despite the sustained hypothermia. Cold exposure blocked the stimulatory effect of morphine on prolactin secretion in rats that were tolerant to the hypothermic effect of morphine. Thus hypothermia caused by morphine, dexmedetomidine, and m-CPP during cold exposure is not the sole factor in the antagonistic effect of cold. We suggest that cold exposure releases some compound(s) modulating hypothalamic neural pathways.
Pulmonary embolism: analysis of endothelial pore sizes in canine lung
Authors: Townsley M. I. , Parker J. C. , Longenecker G. L. , Perry M. L. , Pitt R. M. , Taylor A. E.
Published: December 2017

The effect of glass-bead microemboli (diameter 100 micron, range 77-125 micron) in the absence of fibrinolysis inhibition on pulmonary hemodynamics and microvascular permeability was determined in anesthetized, microfilaria-free dogs acutely prepared for the collection of lung lymph. Pulmonary vascular resistance, pulmonary capillary pressure (Pc), lymph flow (QL), and the ratio of lymph (CL) to plasma (Cp) protein concentrations were measured after 0.2 (n = 4), 0.4 (n = 6), or 0.6 (n = 3) g/kg beads. In all cases, emboli increased resistance and QL severalfold (P less than 0.05), while CL/Cp remained unchanged. In part, the increase in QL could be attributed to an increase in Pc compared with control (12.4 +/- 2.2 vs. 6.7 +/- 0.6 mmHg, P less than 0.05). Furthermore, since the solvent-drag reflection coefficient (sigma f) for total proteins approaches the osmotic reflection coefficient (sigma d) at high QL, sigma d was estimated under these conditions with sigma f approximately equal to sigma d approximately equal to 1 - (CL/Cp)min. The sigma d was decreased (P less than 0.05) after 0.4 and 0.6 g/kg beads to 0.55 +/- 0.03 and 0.50 +/- 0.07, respectively, when compared with that in control lungs (sigma d = 0.62 +/- 0.02; Parker et al., Circ. Res. 48: 549-561, 1981). A pore-stripping analysis demonstrated that after emboli the pulmonary endothelial barrier could be described by a population of small (80 A) and large (350 A) pores. However, the number of large to small pores was 1:1,195, compared with 1:195 in control lungs, suggesting an increased contribution of extra-alveolar vessels upstream of the emboli.(ABSTRACT TRUNCATED AT 250 WORDS)
Epinephrine potentiates human platelet activation but is not an aggregating agent
Authors: Lanza F. , Beretz A. , Stierle A. , Hanau D. , Kubina M. , Cazenave J. P.
Published: December 2017

Epinephrine can in certain in vitro conditions induce the aggregation of human platelets and could play an important role in vivo in the appearance of thrombotic disorders when catecholamine levels are increased. This study examines some functional and biochemical responses to epinephrine. Epinephrine induces the aggregation and serotonin secretion of human platelets in citrated plasma. This is not due to a direct effect of citrate itself, such as the lowering of plasma free Ca2+ but more likely to the generation of traces of thrombin during blood collection, as suggested by abrogation of these platelet responses when hirudin was added before citrate. When washed human platelets suspended in Tyrode buffer containing 2 mM Ca2+, 0.35% albumin and apyrase, and 0.1-100 microM epinephrine were used, no shape change, aggregation, or secretion of serotonin was observed, nor was the platelet ultrastructure modified. Epinephrine does not modify platelet membrane fluidity, as studied with the lipophilic fluorescent probe trimethylammonium-diphenylhexatriene. It has no direct effect on fibrinogen binding to intact platelets, intracellular Ca2+ levels measured by quin2, or protein phosphorylation. Epinephrine potentiates the action of all types of aggregating agents on aggregation, secretion, intracellular Ca2+ levels, membrane fluidity, fibrinogen binding, or protein phosphorylation. These effects are mediated by alpha 2-adrenergic agonists and inhibited by alpha 2-adrenergic antagonists. This study shows that epinephrine alone does not induce modifications of morphology, metabolism, or function of intact and functional washed human platelets and that it cannot be considered per se as an aggregating agent. However, epinephrine interacts with alpha 2-adrenergic receptors on human platelets and potentiates biochemical and aggregatory responses induced by other platelet agonists.
Cardiorespiratory effects of DL-homocysteic acid in caudal ventrolateral medulla
Authors: Bonham A. C. , Jeske I.
Published: December 2017

We carried out experiments in urethan-anesthetized rats to determine 1) whether increasing the activity of small groups of neurons in the caudal ventrolateral medulla (CVLM) by injecting picomoles of an excitatory amino acid altered cardiovascular and/or respiratory homeostasis and 2) whether the depressor responses after chemical excitation in the CVLM were elicited only from the immunohistochemically identified catecholamine-containing cell group. In discrete sites in the CVLM, unilateral injections of 1-12 nl (20-240 pmol) of DL-homocysteic acid (DLH; 20 mM, pH 7.4) selectively or concomitantly inhibited arterial pressure, heart rate, and diaphragm electromyogram (EMG) activity. In the region in which chemical excitation slowed breathing, units were recorded extracellularly that discharged with respiratory periodicity. Sites where the smallest volumes of DLH decreased arterial pressure were located outside the immunohistochemically identified DBH-positive cell bodies. These data suggest that either the same or neighboring neurons in the CVLM are involved in the central neural circuitry for both cardiovascular and respiratory control and that cells other than the catecholaminergic cell group are important in medullary depressor responses.
Coronary vascular responses to chemical stimulation of abdominal visceral organs
Authors: Martin S. E. , Pilkington D. M. , Longhurst J. C.
Published: December 2017

Topical application of bradykinin or capsaicin to abdominal visceral organs produces adrenergically mediated, reflex increases in mean arterial pressure and cardiac work. To determine the effects on coronary blood flow, the left main coronary artery of anesthetized cats was perfused at constant pressure with a servo-controlled pump. Cardiovascular parameters were measured during reflex stimulation before and after beta-adrenoceptor blockade with propranolol. Before propranolol, reflex activation led to increases in the double product and myocardial oxygen consumption, usually accompanied by increases in coronary blood flow. However, in 32% of the observations, decreases in flow were observed. During beta-adrenoceptor blockade, reflex stimulation produced increases in cardiac work, whereas the increases in coronary blood flow were attenuated. Marked decreases in average coronary blood flow were observed more frequently (42%). In the presence of propranolol, contrary to the unblocked state, increases in oxygen consumption were achieved by increased oxygen extraction. Subsequent alpha-adrenoceptor blockade with phentolamine abolished all reflex changes. These data indicate that during stimulation of abdominal visceral chemoreceptors, the major coronary response is vasodilation, but in a sizable fraction of cases, abdominal visceral reflexes can produce sympathetically mediated coronary vasoconstriction.