bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin II and alpha-agonist. III. In vitro fetal-maternal placental prostaglandins
Authors: Yoshimura T. , Rosenfeld C. R. , Magness R. R.
Published: December 2017

In fetal sheep, angiotensin II, but not phenylephrine, increases umbilical venous concentrations of prostaglandin E2 (PGE2) and prostacyclin (PGI2); however, their source(s) is unknown. We sought to determine the tissue source(s) of this increase in prostanoids and to compare responses in fetal and maternal tissues. Fetal placental arteries (PA) and veins (PV), mesenteric arteries (MA) and cotyledons, and maternal caruncles and uterine arteries (UA) from eight pregnant ewes [127 +/- 3 (SE) days] were incubated (37 degrees C, 1 h) in Krebs-Henseleit (95% O2-5% CO2) with or without angiotensin II, phenylephrine, or norepinephrine (5 x 10(-10) and 5 x 10(-8) M). Basal PGE2 production exceeded PGI2 in PA, cotyledons, and caruncles (P less than 0.05), whereas PGE2 less than PGI2 only in UA; production of both prostanoids was greatest in MA with 34.8 +/- 5.0 and 27.4 +/- 3.7 pg.micrograms protein-1.h-1, respectively (P less than 0.001). Caruncles produced little of either prostanoid. Angiotensin II increased PA PGE2 production from 6.5 +/- 1.5 to 8.4 +/- 3.0 and 10.8 +/- 4.5 pg.micrograms-1.h-1 (P = 0.001) and PGI2 from 3.3 +/- 0.5 to 5.5 +/- 1.5 (P less than 0.05) and 3.7 +/- 0.9 pg.micrograms-1.h-1; PV PGE2 rose from 4.5 +/- 1.1 to 9.0 +/- 3.5 and 7.9 +/- 2.3 pg.micrograms-1.h-1 (P less than 0.05); PV PGI2 was unchanged. Angiotensin II increased UA PGE2 from 1.5 +/- 0.3 to 3.4 +/- 1.2 (P less than 0.05) and 2.4 +/- 0.8 pg.micrograms-1.h-1 and PGI2 from 8.7 +/- 1.0 to 12.4 +/- 2.2 and 16.2 +/- 5.2 (P less than 0.05) pg.micrograms-1.h-1. Angiotensin II had no effect on MA, cotyledonary, or caruncular prostanoids. alpha-Agonist had no effect on any tissue examined. In fetal sheep, angiotensin II-induced increases in PGI2 and PGE2 are likely of vascular origin.
Effect of endurance training on sedentary energy expenditure measured in a respiratory chamber
Authors: Schulz L. O. , Nyomba B. L. , Alger S. , Anderson T. E. , Ravussin E.
Published: December 2017

The effect of endurance training on 24-h energy expenditure (EE), basal metabolic rate (BMR), sleeping metabolic rate (SMR), and the thermic effect of food (TEF) was assessed in a respiratory chamber where only spontaneous physical activity (SPA) was allowed. Results from 20 highly trained male endurance athletes (25 +/- 5 yr, 178 +/- 7 cm, 70 +/- 8 kg body wt, 64 +/- 7 kg fat-free mass) were compared with those of 43 untrained males who were matched for age (28 +/- 6 yr), height (175 +/- 5 cm), weight (73 +/- 13 kg), and fat-free mass (62 +/- 8 kg). Subjects were admitted to a metabolic ward, fed a weight-maintenance diet, and refrained from physical activity for at least 2 days before measurements. No significant differences were found with respect to 24-h EE (2,126 +/- 186 vs. 2,154 +/- 245 kcal), BMR (1,808 +/- 342 vs. 1,709 +/- 329 kcal), SMR (1,523 +/- 120 vs. 1,555 +/- 188 kcal), or TEF (24.9 +/- 9.2 vs. 21.3 +/- 6.7% of ingested calories; these values included the energy cost of arousal) between trained and untrained subjects, respectively, before or after adjusting for differences in body composition. Neither the 24-h respiratory quotient nor the level of SPA differed between the two groups. No relationship was found between maximal aerobic capacity and metabolic rate adjusted for differences in fat-free mass and fat mass. These results do not support an effect of fitness level on EE measured under sedentary conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Glycine turnover and oxidation and hepatic serine synthesis from glycine in fetal lambs
Authors: Cetin I. , Fennessey P. V. , Quick A. N. , Marconi A. M. , Meschia G. , Battaglia F. C. , Sparks J. W.
Published: December 2017

[1-13C]- and [1-14C]glycine were infused into chronically catheterized fetal lambs via a brachial vein. At tracer glycine steady state, samples were collected from the fetal abdominal aorta, umbilical vein, and fetal hepatic vein and from the maternal femoral artery and uterine vein. The samples were analyzed for plasma glycine and serine, for glycine and serine 13C atom% excess (APE), and for whole blood 14CO2 and O2 concentrations. Fetal plasma glycine disposal rate (DR) was 12.4 +/- 0.8 mumol.min-1.kg fetus-1.CO2 production from decarboxylation of fetal plasma glycine was 1.63 +/- 0.16 mumol.min-1.kg fetus-1 and represented 12.3 +/- 0.7% of DR. Approximately 50% of infused tracer glycine was taken up by the fetal liver with the release of labeled serine and CO2 in the fetal circulation. There was no detectable efflux of tracer glycine from the placenta into the maternal circulation. The tracer production of serine and CO2 accounted for 23 and 17%, respectively, of the hepatic tracer glycine uptake. The labeled CO2 released by the liver was a large fraction (approximately 70%) of the labeled CO2 produced by the fetus. The serine-to-glycine APE ratio in fetal plasma was approximately 5%. These results indicate that the fetal liver is the major site of fetal plasma glycine decarboxylation and of serine synthesis from plasma glycine.
Suppression of insulin-like growth factor I during epidermal growth factor-induced growth retardation
Authors: Chernausek S. D. , Dickson B. A. , Smith E. P. , Hoath S. B.
Published: December 2017

Epidermal growth factor (EGF) attenuates growth when administered to rats less than 2 wk of age but lacks growth-retarding properties when given to older animals. Because the insulin-like growth factors (IGF) are postulated to be important regulators of somatic growth during the perinatal period, we examined the effect of exogenous EGF on serum and tissue concentrations of IGF-I and hepatic expression of mRNA for IGF-I and IGF-II. A single injection of EGF (500 ng/g body wt) produced a significant (P less than 0.01) decline in serum IGF-I concentration within 4 h in newborn rat pups [controls, 46.2 +/- 9.1 (SD) ng/ml; EGF treated, 29.4 +/- 4.0 ng/ml] but was ineffective in 2-wk-old animals (control IGF-I, 72.8 +/- 15.1 vs. 64.0 +/- 13.7 ng/ml). When the EGF was given on days 0-3 of life, circulating IGF-I concentrations were suppressed further (control, 61.4 +/- 8.6; EGF treated, 32.5 +/- 8.6 ng/ml). Despite the change in circulating IGF-I levels in the newborn rats, the amount of IGF-I extractable from liver and kidney of growth-retarded animals was not significantly different from control. Likewise, IGF-I and IGF-II mRNA expression in liver, as assessed by blot hybridization, was unchanged by the EGF treatment. The rapid decline in IGF-I concentration after EGF administration, coupled with the restriction of this phenomenon the first 2 wk of extrauterine life, implies that changes in IGF-I are involved in the pathogenesis of EGF-induced growth retardation.
CNS stimulation does not affect hepatic venous glucose concentration in severely diabetic rats
Authors: Miura H. , Iguchi A. , Uemura K. , Yatomi A. , Tamagawa T. , Sakamoto N.
Published: December 2017

To assess the role of the central nervous system (CNS) in carbohydrate metabolism in diabetes, neostigmine was injected into the third cerebral ventricle in fed rats with streptozotocin (STZ; 80 mg/kg)-induced diabetes under pentobarbital sodium anesthesia. Changes in hepatic venous plasma glucose concentrations were monitored. Neostigmine injection caused no significant changes in the hepatic venous plasma glucose concentration in untreated diabetic rats, whereas the glucose level increased significantly in insulin-treated diabetic rats similarly to the changes in normal control animals. In diabetic rats, the plasma levels of glucagon, epinephrine, and norepinephrine were increased significantly by neostigmine. After various doses (35-80 mg/kg) were given to rats, it was found that the higher the STZ dose, the lower was the hepatic glycogen content and the smaller was the glycemic response to neostigmine. Our results indicate that, in severe diabetes, CNS stimulation with neostigmine fails to increase hepatic glucose output, because glycogen stores are nearly exhausted and gluconeogenesis is already maximal.
Decreased expression of glucose transporter in muscle from insulin-resistant patients
Authors: Dohm G. L. , Elton C. W. , Friedman J. E. , Pilch P. F. , Pories W. J. , Atkinson S. M. , Caro J. F.
Published: December 2017

We have observed that in vitro incubated human muscle fiber strips from obese patients with or without non-insulin-dependent diabetes mellitus (NIDDM) have reduced insulin-stimulated glucose transport rates compared with nonobese control patients. To investigate if the decrease in glucose transport is associated with a depletion of glucose transport protein, we performed Western blot analysis of muscle samples from nonobese control, obese nondiabetic, and obese NIDDM patients to measure the levels of the muscle-adipose tissue glucose transporter (GLUT-4) protein. Glucose transporter protein was depressed by 23% in the obese nondiabetic and 18% in the obese NIDDM group. The results were essentially the same in the rectus abdominus and vastus lateralis muscles. These data suggest that the decreased glucose transport rate observed in muscle of these obese patients with or without NIDDM may be due, at least in part, to a decreased expression of the "insulin-sensitive" (GLUT-4) glucose transporter. This alteration may play a role in the insulin resistance seen in obesity and diabetes.
Effect of dietary calcium on bone density in growing rabbits
Authors: Gilsanz V. , Roe T. F. , Antunes J. , Carlson M. , Duarte M. L. , Goodman W. G.
Published: December 2017

Reductions in peak bone mass at skeletal maturity may increase the risk for the subsequent development of osteoporosis. Although changes in calcium intake can modify the rate of decline in bone density in the mature skeleton, longitudinal assessments of the effect of dietary calcium supplementation during skeletal growth on peak bone mass have not been done in humans or experimental animals. Thus quantitative computed tomography (QCT) was used to monitor changes in vertebral bone density at 6-wk intervals during growth from 8 wk of age until skeletal maturity at 35 wk in male New Zealand White rabbits maintained on diets containing 0.15% (low Ca), 0.45% (normal Ca), or 1.35% (high Ca) calcium. Serum parathyroid hormone (PTH) and calcitriol levels increased, and renal calcium excretion decreased in low Ca compared with normal Ca; in contrast, serum calcitriol levels decreased and renal calcium excretion increased from control values in high Ca. Vertebral bone density by QCT did not differ during growth between high Ca and normal Ca, and peak values at epiphyseal closure also did not differ in these two groups. Vertebral bone density was lower, however, throughout the study in low Ca, and peak values at epiphyseal closure remained below those in either normal Ca or high Ca. Quantitative bone histology revealed decreases in cortical thickness in the third lumbar vertebra in low Ca, whereas trabecular bone area did not differ among groups; there was no histological evidence of osteomalacia in low Ca. Thus dietary calcium restriction during growth reduces peak bone mass at skeletal maturity, but raising dietary calcium intake above normal levels does not increase peak bone mass in this experimental model.
Age-related alterations in pulsatile secretion of TSH: role of dopaminergic regulation
Authors: Greenspan S. L. , Klibanski A. , Rowe J. W. , Elahi D.
Published: December 2017

To investigate the influence of aging on dopaminergic modulation of pulsatile thyrotropin (TSH) secretion, we examined changes in circulating TSH levels during the day and night, with and without a dopamine antagonist metoclopramide, in healthy young (20-35 yr old) and old (69-83 yr old) subjects, with the use of cluster analysis. Baseline thyroid function tests including serum thyroxine, 3,5,3'-triiodothyronine (T3), T3 resin uptake, and TSH and the response of TSH to thyrotropin-releasing hormone were within normal limits in young and old subjects, and antimicrosomal and anti-thyroglobulin antibodies were absent in all participants. Pulsatile TSH secretion was identified in all subjects, and as a group there were significant increases in nocturnal peak height (P less than 0.01), amplitude (P less than 0.01), and mean TSH (P less than 0.001). TSH pulse amplitude increased 160% (P less than 0.05) at night compared with day in the young but was unchanged at night in the old. After the administration of metoclopramide there was a significant increase in peak height (P less than 0.01), amplitude (P less than 0.01), and mean TSH (P less than 0.01). However, the effect of metoclopramide was different in young and old subjects. In the young, daytime administration of metoclopramide increased TSH pulse height (P less than 0.02) and mean TSH (P less than 0.05); pulse parameters remained unchanged at night. In comparison, in old subjects after metoclopramide, pulse parameters were unchanged during the day but pulse amplitude significantly (P less than 0.01) increased at night. TSH pulse frequency remained stable with age and was unaltered after metoclopramide.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased pyruvate dehydrogenase kinase activity in response to sepsis
Authors: Vary T. C.
Published: December 2017

The effect of sterile inflammation and sepsis on the proportion of active pyruvate dehydrogenase complex (PDH) in mitochondria isolated from skeletal muscle has been investigated. The proportion of active PDH in mitochondria isolated from septic animals was significantly reduced compared with control under all incubation conditions examined, even in the presence of inhibitors of the PDH kinase. There was no significant difference between control and sterile inflammation in any of the incubations examined. The rate constant for ATP-dependent inactivation of the PDH complex in mitochondrial extracts from control animals was -0.42 min-1 (r = 0.993; P less than 0.001) and was not altered in mitochondrial extracts from sterile inflammatory animals (-0.43 min-1; r = 0.999; P less than 0.001). However, rate constants for inactivation in septic animals was significantly increased over twofold to -1.08 min-1 (r = 0.987; P less than 0.001) (P less than 0.001 vs. control or sterile inflammation). In the presence of inhibitors of the PDH kinase reaction (2.5 mM pyruvate or 1 mM dichloroacetate), inactivation of PDH after addition of ATP was significantly greater in mitochondrial extracts from septic than either control or sterile inflammatory animals. These results suggest that sepsis, but not sterile inflammation, induces a stable factor in skeletal muscle mitochondria that increased PDH kinase activity.
Responses of protein synthesis in different skeletal muscles to fasting and insulin in rats
Authors: Baillie A. G. , Garlick P. J.
Published: December 2017

The rate of protein synthesis (Ks) was measured in nine skeletal muscles from young rats (100 g body wt) after fasting and subsequent insulin infusion. An overnight fast (12 h) resulted in a fall in Ks in all muscles, but this ranged from a small nonsignificant decrease in soleus (Sol) to one-half of the fed rate in tensor fascia latae (TFL). After fasting for 36 h, Ks was significantly reduced in all muscles, although there was still a range apparent between different muscles. The response of the individual muscles to fasting was related to fiber type composition, and, in particular, the responses of the commonly studied Sol were characteristic of the highly oxidative fiber composition rather than being peculiar to Sol itself. The magnitude of the increase in Ks during an infusion of insulin (0.5 h) in the 12-h fasted rats was proportional to the magnitude of the initial response to fasting and these changes were largely reflected in changes in the rate of synthesis expressed per unit RNA (KRNA). After 36 h of fasting, Ks in the muscles responded little to the insulin stimulus, and a similar small effect on KRNA, compared with that in the 12-h fasted animals, suggests an apparent insensitivity to insulin after this longer fasting period.
Effect of AVP on susceptibility of ovine pituitary cells to a cytotoxic analogue of CRF
Authors: Schwartz J. , Pham T. , Rao A. , Funder J. W.
Published: December 2017

Although exposure to arginine vasopressin (AVP) has been reported to induce anterior pituitary corticotrophs to bind and become responsive to corticotropin-releasing factor (CRF), the identity of these inducible CRF target cells is unknown. Such cells may themselves be the AVP-responsive corticotrophs or other cells that become CRF targets secondary to a paracrine signal from AVP target cells. The present study used a cytotoxin (Cx), specific for CRF target cells, that eliminates responses of treated cells to a subsequent challenge with CRF but leaves responses to AVP intact. We hypothesized that, if AVP target corticotrophs themselves become CRF targets, then the addition of AVP during treatment with Cx should render these cells susceptible to the cytotoxin and should eliminate the response to subsequent AVP as well. Ovine pituitary cells were chosen for the study because they respond more robustly than rat cells to AVP. Pretreatment of ovine pituitary cells with Cx (400 pM) or Cx plus AVP (10 nM) eliminated the adrenocorticotropic hormone (ACTH) secretory response to CRF (10 nM), as assessed 3 days later. Cx alone also reduced the secretory response to AVP from 23.9 +/- 3.4 to 11.5 +/- 1.9 ng ACTH/3 h (P less than 0.05). However, pretreatment with AVP (10 nM) plus Cx caused no further reduction in the secretory response to AVP (10.1 +/- 2.6 ng ACTH/3 h). These data suggest that, if AVP induces erstwhile non-CRF target cells to become CRF targets, then these induced cells are not themselves initially AVP target corticotrophs.
Heterogeneous response to PTH in aging rats: evidence for skeletal PTH resistance
Authors: Fox J. , Mathew M. B.
Published: December 2017

Plasma immunoreactive parathyroid hormone (irPTH) levels increase and renal responsiveness to pharmacological doses of PTH decreases with advancing age. This study tested whether 1) decreased irPTH clearance contributes to the elevated NH2-terminal irPTH levels seen in aged rats and 2) aged rats respond to physiological levels of rat PTH. Conscious adult (7-mo-old) and aged (25-mo-old) male Sprague-Dawley rats were infused for 2 h with rat PTH-(1-34) to achieve steady-state levels in plasma (110-120 pg/ml). Basal irPTH levels were 77% higher (P less than 0.01), and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels were 46% lower (P less than 0.05) in the aged rats. Renal function was not significantly different in these two groups. The metabolic clearance rate of irPTH was rapid and not different in adult and aged rats (99 +/- 8 vs. 111 +/- 7 ml.min-1.kg-1, respectively). After the PTH infusion, plasma ionized and total calcium and 1,25(OH)2D3 levels increased significantly in adult rats, whereas no changes were observed in aged rats. In contrast, a similar significant hypophosphatemic response (23-25% decrease) was seen in both age groups, but the hypophosphatemia was maintained for longer in aged rats. Thus the elevated plasma irPTH levels in aged rats are caused solely by increased secretion. Finally, there is a heterogeneity in the responses to PTH infusion in aged rats, suggesting that the aged rat skeleton, like the kidney, is PTH resistant.
Role of free fatty acids in hepatic insulin resistance during late pregnancy in conscious rabbits
Authors: Gilbert M. , Pere M. C. , Baudelin A. , Battaglia F. C.
Published: December 2017

This study addresses whether elevated free fatty acids (FFA) contribute to the hepatic insulin resistance of pregnancy. We applied a euglycemic hyperinsulinemic clamp with or without Intralipid plus heparin infusion in conscious virgin and pregnant rabbits after an 18-h fast coupled with chronic catheterization of the hepatic and portal veins and femoral artery. A primed constant infusion of [3-3H]glucose was used to determine glucose fluxes. Insulin was infused into a mesenteric vein for 140 min. In pregnant rabbits, basal net hepatic uptake of lactate was almost two times that of nonpregnant rabbits. During a euglycemic hyperinsulinemic clamp there was a decline of approximately 65% in hepatic lactate uptake in nonpregnant rabbits at 80 min, whereas a similar decrease was observed only at 140 min in pregnant rabbits. This effect was blocked by lipid infusion. In the basal state the hepatic uptake of FFA was greater in pregnant than in nonpregnant animals. During the hyperinsulinemic clamp the hepatic uptake dropped by approximately 70 and approximately 30% in nonpregnant and pregnant females, respectively. Lipid infusion did not prevent the hepatic FFA uptake and hepatic ketone body output from decreasing. Hepatic glucose production was totally suppressed in the control period in nonpregnant animals but not during lipid infusion (approximately 65%). Hepatic glucose production was not significantly different between pregnant and nonpregnant rabbits during lipid infusion. Glucose utilization was markedly reduced in nonpregnant animals during lipid infusion to levels comparable with that in pregnant animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Splanchnic osmosensation and vasopressin: mechanisms and neural pathways
Authors: Choi-Kwon S. , Baertschi A. J.
Published: December 2017

Hypertonic (2 ml, 598 mosmol/kgH2O) solutions were infused over 4 min via a stomach tube in 12 groups (n = 5-10) of conscious rats with indwelling arterial catheters. Mean changes over 4–21 min of plasma arginine vasopressin (AVP) were 6.1 +/- 0.9 for NaCl (P less than 0.01), 9.3 +/- 3.0 for LiCl (P less than 0.01), 4.5 +/- 1.3 for sodium isethionate (P less than 0.01), 2.8 +/- 0.9 for sucrose (P less than 0.025), 3.9 +/- 2.8 for mannitol (P less than 0.01), and -0.1 +/- 0.1 (SE) pg/ml for urea. The AVP responses to NaCl and sucrose were proportional to the rate of gastrointestinal absorption of radiolabeled NaCl and sucrose, respectively. The AVP response to 598 mosmol/kgH2O NaCl was attenuated by 60.6% (P less than 0.001) in rats with lesion of the side branches of the major splanchnic nerves innervating the mesentery of the upper small intestine and the portal vein area, by 34–37% (P less than 0.05) in rats with right or left splanchnic nerve lesions, and was not affected by subdiaphragmatic vagotomy. Changes in systemic plasma osmolality were small and could not explain the AVP responses. Thus splanchnic receptors are osmosensitive, are situated in the mesentery of the upper small intestine and possibly the portal vein area, and project to the spinal cord via the right and left major splanchnic nerves.
Metabolism of oleic acid in differentiating BFC-1 preadipose cells
Authors: Abumrad N. A. , Forest C. , Regen D. M. , Barnella U. S. , Melki S. A.
Published: December 2017

Incorporation of [3H]oleate and [14C]glucose into cellular lipids was studied in the preadipose cell line BFC-1 to determine flux changes that accompany the adipose conversion process. Dilution of oleate by intracellular fatty acids (FA) was estimated from the 3H/14C incorporation ratios and from relating steady-state radioactivity in diglycerides to their measured cellular levels. The data indicated that exogenous FA mixed with less than 1% of endogenous FA on its pathway to esterification. Conversion of preadipocytes to adipocytes increased uptake of FA and glucose by approximately 3-fold and synthesis of diglycerides and triglycerides by 5- and 16-fold, respectively, with little if any increase of phospholipid synthesis. A 50% drop in 3H/14C incorporation ratio indicated a doubling of the rate at which endogenous FA mixed with the exogenous FA that had entered the cell. Adipocytes compared with preadipocytes exhibited a 50% greater cell diameter and a doubling of intracellular water volume and of protein and phospholipid levels, reflecting cellular enlargement consequent to the arrest of cell division that precedes adipose conversion. Diglyceride levels were also increased in adipocytes, however, since their turnover was fast, as indicated by rapid equilibration of diglyceride labeling; the increase reflected changes in their relative rates of synthesis and disposal. Diglyceride levels related to cell phospholipid, and other indexes of cell size remained constant. This indicated that the supply of diglycerides was tightly coupled to the synthesis of triglycerides and phospholipids, which suggested feedback regulation of diglyceride formation. The studies provide a methodological approach to measurement and interpretation of rates of lipid deposition in cultured cells.
Effects of thyroid hormones on urinary and renal kallikreins
Authors: Avigdor S. , Alhenc-Gelas F. , Bouhnik J.
Published: December 2017

The effects of thyroid hormones on the urinary excretion of kallikrein and on renal kallikrein were studied in rats. Total and active urinary kallikrein was decreased after thyroidectomy, but renal kallikrein content remained unchanged. Diuresis increased, and kidney weight and plasma aldosterone concentration decreased. Treatment with 3,5,3'-triiodo-L-thyronine restored the urinary kallikrein in thyroidectomized rats to normal and increased it in intact rats. It also produced increases in kidney weight and plasma aldosterone and a decrease in diuresis. The effect of thyroid hormones on the urinary kallikrein response to mineralocorticoids was also tested. Deoxycorticosterone acetate increased urinary kallikrein more in normal than in thyroidectomized rats. These results suggest that thyroidectomy decreases renal kallikrein synthesis and lowers the turnover rate of the enzyme, changes not detectable by a single measurement of the renal kallikrein content but reflected by an alteration in the urinary excretion of the enzyme. Thyroid hormones participate in the control of urinary kallikrein. This effect, however, is probably indirect and may be mediated by mineralocorticoids since thyroid function affects both the plasma level of aldosterone, which is known to influence renal kallikrein, and the kallikrein response to exogenous mineralocorticoids.
Stimulation of protein synthesis in pig skeletal muscle by infusion of amino acids during constant insulin availability
Authors: Watt P. W. , Corbett M. E. , Rennie M. J.
Published: December 2017

Incorporation of L-[1-13C]leucine into muscle protein and leg exchange of L-[15N]phenylalanine were used to assess the effects over 240 min of amino acid supply on leg protein turnover in anesthetized, overnight-fasted (Landrace x Great White) female pigs. In all pigs, plasma insulin and glucagon stability was ensured by infusion of somatostatin (8 micrograms.kg-1.h-1), insulin (6 mU.kg-1.h-1), and glucagon (72 ng.kg-1.h-1). Mixed amino acid infusion (260 mg.kg-1.h-1) caused a 2- to 2.5-fold elevation of arterial plasma phenylalanine and leucine; in a control group (no amino acid infusion), an increase in phenylalanine and leucine concentration was observed as a result of the hormone clamp. Plasma insulin and glucagon concentrations were steady and not significantly different between control and amino acid-infused groups during the final 240 min, but plasma glucose fell (P less than 0.05) in both groups (4.57 +/- 0.17 to 3.15 +/- 0.73 mM). Muscle protein synthetic rate (estimated from the change in L-[1-13C]leucine incorporation compared with labeling of [13C]leucyl-tRNA) was greater in amino acid-infused (0.076%/h) than in control (0.053%/h) pigs. In the control group, leg amino acid balance was negative (Phe alone, -10.2 +/- 9.4 nmol Phe.100 g-1.min-1; total amino acids, -0.27 +/- 1.04 micrograms amino N.100 g-1.min-1), but during amino acid infusion, balance was positive (Phe alone, +33.6 +/- 8.8 nmol Phe.100 g-1.min-1; total amino acids, +58.2 +/- 4.9 micrograms amino N.100 g-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of long-term rhGH administration in GH-deficient adults on fat cell epinephrine response
Authors: Beauville M. , Harant I. , Crampes F. , Riviere D. , Tauber M. T. , Tauber J. P. , Garrigues M.
Published: December 2017

Besides exerting its own lipolytic effect, growth hormone (GH) has been reported to potentiate the lipolytic response of adipose tissue to epinephrine. It was thought interesting to find out whether long-term recombinant human growth hormone (rhGH) administration modifies epinephrine-induced lipolysis in isolated adipocytes of GH-deficient adults. In a double-blind protocol, GH-deficient subjects received either 6 mo placebo (controls, n = 5) or 6 mo rhGH (treated, n = 5). Biopsies of fat were obtained from the periumbilical region before and after placebo or rhGH administration. The response of the collagenase-isolated fat cells to various concentrations of epinephrine was assessed by glycerol release, measured by bioluminescence. Epinephrine-induced lipolysis was not altered by 6 mo placebo, while it was significantly increased by 6 mo rhGH. A similar response was obtained with isoproterenol, but no significant differences occurred in either group with UK 14304, an alpha 2-adrenoreceptor agonist. Thus, in GH-deficient adults, long-term rhGH administration improves the lipolytic response of isolated adipocytes to epinephrine, essentially by increasing the efficiency of the beta-adrenergic pathway.
Importance of basal glucagon in maintaining hepatic glucose production during a prolonged fast in conscious dogs
Authors: Hendrick G. K. , Wasserman D. H. , Frizzell R. T. , Williams P. E. , Lacy D. B. , Jaspan J. B. , Cherrington A. D.
Published: December 2017

We undertook studies in conscious dogs to assess the role of basal glucagon in stimulating glucose production after a 7-day fast. Two protocols consisting of a 40-min basal period (-40 to 0 min), and a 180-min test period (0-180 min) were used. During the test period of the first protocol (hormone replacement; n = 4), somatostatin was infused (0.8 micrograms.kg-1.min-1) along with basal intraportal replacement amounts of insulin and glucagon, whereas in the second protocol (glucagon deficiency; n = 5), somatostatin plus insulin alone were infused. Glucose production and gluconeogenesis were measured using tracer and arteriovenous difference techniques. Plasma insulin levels were similar during the test period in both protocols (6 +/- 1 microU/ml). The plasma immunoreactive glucagon level in the control protocol averaged 50 +/- 8 pg/ml, whereas in the glucagon-deficiency protocol the level fell from 50 +/- 8 to 29 +/- 8 pg/ml (P less than 0.05). The plasma glucose level and the rate of glucose production were unchanged during bihormonal replacement. During glucagon deficiency the plasma glucose level was held constant at 100 +/- 4 mg/dl by glucose infusion. Tracer-determined endogenous glucose production fell from 1.8 +/- 0.1 to 1.0 +/- 0.1 mg.kg-1.min-1 by 30 min (P less than 0.05). After 3 h of glucagon deficiency, gluconeogenic conversion of alanine to glucagon was reduced 40% and the hepatic fractional extraction of alanine was reduced by 45%. The efficiency of the gluconeogenic process within the liver was not altered by glucagon deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
Four proteolytic processes of myocardium, one insensitive to thiol reactive agents and thiol protease inhibitor
Authors: Thorne D. P. , Lockwood T. D.
Published: December 2017

Four distinct processes mediating protein degradation were identified in the Langendorff perfused rat heart. Hearts were biosynthetically labeled in vitro with [3H]leucine for 10 min. The subsequent release of [3H]leucine at 1.5-min intervals (2 mM nonradioactive leucine) was determined from 20 min to 8 h after labeling in rhythmically contracting hearts. Rapid turnover proteins were eliminated during the first 3 h; this degradation was not inhibited by insulin (5 nM) or isoproterenol (0.5 microM). However, the nontoxic thiol reactive agent diamide (100 microM) caused a complete inhibition of the [3H]leucine release from rapidly degraded proteins. After the elimination of rapidly degraded proteins at 3 h, the release of [3H]leucine was inhibited 35-40% by insulin (5 nM) or the lysosomal inhibitor chloroquine (30 microM), thereby defining a second vesicular process. The beta-agonist isoproterenol (0.5 microM) or the nonselective alpha-agonist naphazoline (100 microM) caused 30-35% proteolytic inhibitions, defining a third adrenergic-responsive process. The inhibitory effects of simultaneously combined insulin and chloroquine did not exceed the effect of either agent alone. However, the combined effects of insulin and isoproterenol were additive, inhibiting two-thirds of basal degradation. Beginning at 3 h after labeling a 75% proteolytic inhibition resulted from the thiol reactive agents diamide (100 microM) or N-ethylmaleimide (10 microM); the thiol protease active site inhibitor trans-epoxysuccinly-L-leucylamino-(4-quinidino)butane (50 microM) caused 65% inhibition. The 75% inhibition caused by diamide includes both the insulin-responsive and beta-adrenergic-responsive pathways. A novel fourth proteolytic process (25% of proteolysis) was thereby distinguished from the above three by its resistance to inhibition by insulin, adrenergic agonists, thiol reactive agents, or thiol protease inhibitor. Only the adrenergic-responsive process was correlated with changes in contractile rhythm or fibrillation.
Distribution of PYY receptors in human fat cells: an antilipolytic system alongside the alpha 2-adrenergic system
Authors: Castan I. , Valet P. , Larrouy D. , Voisin T. , Remaury A. , Daviaud D. , Laburthe M. , Lafontan M.
Published: December 2017

The antilipolytic effect of peptide YY (PYY) and neuropeptide Y has recently been shown in human adipocytes. PYY receptors were investigated in three human adipose deposits. A greater number of 125I-labeled PYY binding sites was found in femoral adipocyte membranes (maximal binding = 40 +/- 4 fmol/mg protein; dissociation constant = 0.3 +/- 0.1 nM) when compared with mammary and pericolonic adipose tissue. PYY receptors, like alpha 2-adrenergic sites, were largely expressed in femoral fat cells. Such a distribution was not specific either to inhibitory or to stimulating adenylyl cyclase systems since adenosine A1 and beta-adrenergic receptors were more numerous in pericolonic adipocytes. On isolated adipocytes, PYY (10(-7) M) inhibited lipolysis by 58 +/- 2% in femoral and 14 +/- 4% in pericolonic fat cells; epinephrine had the following similar response: 62 +/- 5 and 26 +/- 8%, respectively. A close relationship between the number of alpha 2-sites and PYY sites and the antilipolytic effects initiated by PYY and an alpha 2-agonist was observed. No significant differences were noted in the amount of Gi proteins in femoral and pericolonic adipocyte membranes.
Hypoglycemia but not hyperglycemia induces rapid changes in pancreatic beta-cell gene transcription
Authors: Giddings S. J. , Carnaghi L. R. , Shalwitz R. A.
Published: December 2017

The purpose of these studies was to quantify several mRNAs expressed specifically in pancreatic islet cells and known or postulated to be important for insulin release after acute well defined alterations in levels of plasma glucose. Glucose levels were maintained at 50, 120, or 180 mg/dl (2.8, 6.7, or 10 mM) for 3 h in conscious unrestrained rats. Hypoglycemia (for 3 h) caused significant decreases in pancreatic content of mRNAs for insulin 2 and GLUT-2 to 55 and 34% of control values, respectively. There were no significant changes in insulin 1, amylin, glucokinase, or glucagon mRNAs. Unprocessed insulin 1 and 2 mRNA precursors were decreased to 17 and 10% of levels in controls, consistent with effects of short-term hypoglycemia on new mRNA synthesis. Hyperglycemia (for 3 h) caused no increase in pancreatic content of any mRNA measured. To discriminate between effects of hypoglycemia and hyperinsulinemia in the hypoglycemic animals, rats were made hypoglycemic by infusion with etomoxir, a carnitine palmitoyltransferase I inhibitor that lowers glucose in the fasted (glycogen-depleted) state by inhibiting hepatic gluconeogenesis. A single dose of this agent caused a decrease in glucose from 120 mg/dl (6.7 mM) to 80 mg/dl (4.4 mM) and significantly decreased insulin mRNA and pre-mRNA. These results are consistent with the hypothesis that glucose modulates islet cell gene transcription directly. They indicate that the range of glucose concentrations that modulate gene transcription differs from the levels of glucose that alter both insulin biosynthetic and secretion rates.
In vitro lipid synthesis in human adipose tissue from three abdominal sites
Authors: Edens N. K. , Fried S. K. , Kral J. G. , Hirsch J. , Leibel R. L.
Published: December 2017

The association between abdominal deposition of adipose tissue and morbidities accompanying obesity may be related to high rates of free fatty acid release from enlarged intra-abdominal stores. To investigate cellular mechanisms that might contribute to enlargement of intra-abdominal adipocytes, lipolysis, triacylglycerol (TG), and diacylglycerol (DG) synthesis from [14C]glucose was measured in abdominal subcutaneous, omental, and mesenteric adipose tissue from severely obese women and men. Subcutaneous adipose tissue from women showed the highest rates of TG synthesis compared with the intra-abdominal site, or any site in men. isoproterenol stimulated TG synthesis more in intra-abdominal than subcutaneous adipose tissue. In the basal state, intra-abdominal adipose tissue from both men and women showed rates of [14C]DG accumulation approximately 50% total [14C]acylglyceride accumulation, whereas, in subcutaneous adipose tissue, [14C]DG accumulation was approximately 25% of total. Basal lipolysis was lower in intra-abdominal than subcutaneous adipocytes. Stimulation of lipolysis reduced [14C]DG accumulation more in intra-abdominal than subcutaneous adipose tissue. Low rates of acylglyceride synthesis in intra-abdominal adipocytes may prevent accumulation of large intra-abdominal fat stores in women.
Effect of hepatic nerves on disposition of an intraduodenal glucose load
Authors: Moore M. C. , Shulman G. I. , Giaccari A. , Pagliassotti M. J. , Cline G. , Neal D. , Rossetti L. , Cherrington A. D.
Published: December 2017

We examined the disposition of a continuous 4-h intraduodenal glucose infusion (8 mg.kg-1 x min-1, labeled with [1-13C]glucose and [3-3H]glucose) in nine conscious hepatic-denervated dogs. Cumulative net hepatic uptakes (in grams of glucose equivalents) were 13.7 +/- 2.5 glucose, 3.1 +/- 0.6 gluconeogenic amino acids, and 0.8 +/- 0.1 glycerol. Net hepatic glycogen synthesis totalled 11.0 +/- 0.9 g, 55-62% via the direct pathway. All values were similar to those in hepatic-innervated dogs. Glycogen synthase activity and rate of glycogen synthesis were positively correlated (r2 = 0.913, P < 0.05). Variability in net hepatic glycogen synthesis and the mass of glycogen synthesized via the indirect pathway was reduced in hepatic-denervated dogs (P < 0.05). In conclusion, the glycemic response and rate of net glycogen synthesis during an intraduodenal glucose infusion was no different in hepatic-denervated and -innervated dogs. Net hepatic glucose uptake was sufficient to account for all net hepatic glycogen synthesis and lactate production, consistent with an intrahepatic source of gluconeogenic precursors for glycogen synthesis via the indirect pathway. Hepatic nerves appear responsible for much of the variability in net hepatic glycogen synthesis and in the mass of glycogen synthesized via the indirect pathway in normal dogs.
Ovine fetal protein metabolism during decreased glucose delivery
Authors: Milley J. R.
Published: December 2017

During decreased fetal glucose delivery, endogenous substrates increasingly support metabolic rate. If oxidation of fetal amino acid stores (i.e., protein) is to provide such substrate, either protein synthesis must decrease or protein breakdown must increase. Both of these changes would diminish fetal protein accretion, an important component of fetal growth. This study was performed, therefore, to find if decreased glucose delivery alters fetal leucine metabolism. Catheters were placed in six sheep fetuses under maternal general anesthesia, and, after 6 days recovery, fetal leucine metabolism was measured by infusion of [1-14C]leucine before and after fetal glucose delivery was decreased by infusing insulin to the ewe. Later (2 days) the experiment was repeated in reverse order. Decreased fetal glucose delivery was associated with a 19% decrease in the rate of fetal leucine disposal (P < 0.001), a 42% decrease in the rate of exogenous leucine uptake (P < 0.01), and no change in the rate of fetal leucine decarboxylation. The use of leucine for protein synthesis by the fetus fell by 23% (P < 0.001), whereas the rate of protein breakdown did not change. Consequently, during decreased fetal glucose delivery, leucine accretion into fetal proteins was 28% (P < 0.02) of the control rate. In summary, fetal oxidation of amino acids derived from increased protein breakdown is not the source of endogenous substrate needed by the fetus with restricted glucose availability. Fetal protein synthesis did decrease, however, diminishing the accretion of leucine into protein.
Leucine metabolism at graded amino acid intakes in children receiving parenteral nutrition
Authors: Goulet O. , DePotter S. , Salas J. , Robert J. J. , Rongier M. , Ben Hariz M. , Koziet J. , Desjeux J. F. , Ricour C. , Darmaun D.
Published: December 2017

To assess the response of protein turnover to graded levels of amino acid (AA) intakes, leucine kinetics were determined in six 8- to 16-yr-old patients in a stable nutritional status receiving home parenteral nutrition (PN) for short-bowel syndrome or intestinal pseudo-obstruction syndrome. Although daily energy intake was kept constant at 68.7 +/- 13 kcal/kg lean body mass (LBM) with 25.4 +/- 3.6% lipid, patients were given, for three consecutive 7-day periods, 0.7, 1.5, or 2.5 g AA.kg LBM-1.day-1, with the order of the regimens being randomized. On day 7 of each period, a 4-h infusion of L-[1-13C]leucine was performed during intravenous feeding; plasma [13C]ketoisocaproate and expired 13CO2 enrichments were used to assess whole body leucine turnover (Ra), oxidation rate (Ox), nonoxidative disposal [an estimate of protein synthesis (S)], and leucine derived from protein breakdown (B). Urine collection (24 h) was performed for determination of nitrogen excretion. Results indicate a dose-dependent rise in plasma leucine concentration, Ra, and Ox but no significant change in B. There was a significant increase of S (P = 0.04 analysis of variance) with increased AA intakes as well as net leucine balance (P = 0.02). Results are consistent with improved leucine balance, when leucine intake increases, despite increased leucine oxidation. The net protein gain observed with higher AA intakes may suggest a beneficial effect for children receiving long-term PN.
Adaptive changes in zonation for gluconeogenic capacity in liver lobules of cold-exposed rats
Authors: Shiota M. , Fujimoto Y. , Inagami M. , Hiramatsu M. , Moriyama M. , Kimura K. , Ohta M. , Sugano T.
Published: December 2017

The rate of gluconeogenesis from lactate increased in perfused livers after exposure of rats to cold for 5 days, and it returned to the control rate after 20 days [M. Shiota, T. Tanaka, and T. Sugano. Am. J. Physiol. 249 (Endocrinol. Metab. 12): E281-E286, 1985.]. The relationship between the increased gluconeogenic activity and its zonal distribution in liver lobules was studied in cold-exposed rats that had been starved for 24 h by examination of preparations enriched for periportal hepatocytes (PP-H) and for perivenous hepatocytes (PV-H), which had been isolated by the digitonin-collagenase perfusion technique. In the control group, the rate of gluconeogenesis from lactate or alanine was three times higher in PP-H than in PV-H. The rate of gluconeogenesis from these substrates in PP-H was not changed by exposure of rats to cold. The rates of PV-H increased to the level in PP-H after 5 days of exposure of rats to cold and then returned to the control rates after 20 days. The rate of gluconeogenesis from fructose was not altered in either preparation of cells by cold treatment of rats. The change in gluconeogenic capacity in PV-H caused by exposure of rats to cold was unrelated to changes in the activity of the malate-aspartate shuttle and of pyruvate kinase. The increased capacity in mitochondrial respiration was observed in both preparations of cells by cold treatment of rats for 5 days. The activity of phosphoenolpyruvate carboxykinase was higher in PP-H than in PV-H in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypothalamic and gastric myoelectrical responses during vection-induced nausea in healthy Chinese subjects
Authors: Xu L. H. , Koch K. L. , Summy-Long J. , Stern R. M. , Seaton J. F. , Harrison T. S. , Demers L. M. , Bingaman S.
Published: December 2017

The physiology of nausea, a uniquely human symptom, is poorly understood. The purpose of this study was to measure the temporal sequences of neurohormonal responses and gastric myoelectrical activity in healthy subjects during the rotation of an optokinetic drum that produced nausea and other symptoms of motion sickness. Plasma catecholamines, vasopressin, and cortisol were measured at baseline, during minutes 1-5, 6-10, and 11-15 of drum rotation, and after rotation stopped. Electrogastrograms were recorded throughout the study. Twelve subjects (80%) developed nausea and 4-9 cycles/min of gastric tachyarrhythmias; three subjects had no nausea and no gastric dysrhythmias. Tachyarrhythmias began 3.4 +/- 0.8 min after the onset of drum rotation, and nausea was reported, on average, 3 min later. During minutes 6-10 of drum rotation, vasopressin levels significantly increased in the subjects with nausea compared with subjects without nausea (P < 0.04). In the subjects with nausea, epinephrine and vasopressin increased significantly (P < 0.05) compared with baseline during minutes 6-10 and 11-15 of drum rotation. As nausea resolved during recovery, vasopressin decreased by 74%, whereas epinephrine increased 13%. We conclude that 1) in nauseated subjects, endogenous vasopressinergic and sympathetic circuits are activated before hypothalamic-pituitary-adrenal pathways, 2) plasma vasopressin levels correlate most closely with the temporal onset and resolution of nausea, and 3) peripheral gastric dysrhythmias may have a role in activating central vasopressinergic neurons.
Characterization of endothelin receptors in the anterior pituitary gland
Authors: Kanyicska B. , Freeman M. E.
Published: December 2017

To characterize endothelin (ET) receptors modulating pituitary hormone secretion, potencies of ET-like agonists were compared on prolactin (PRL), thyrotropin (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) secretion from primary cultures of female rat pituitary cells. ET-1 was more potent than ET-3 in all cases. Sarafotoxin (SRTX) S6b an ETA agonist, was also more potent than ET-3 in all cases. SRTX-c, an ETB receptor agonist, was inactive. The ET-1-to-ET-3 potency ratio was three orders of magnitude higher on PRL or TSH secretion than on LH and FSH secretion, whereas SRTX-b-to-ET-3 potency ratios were similar on all four hormones. The ETA antagonist BQ-123 caused a parallel dextral displacement of dose-response curves of ET-1 and ET-3 on all four hormones. Schild regressions for BQ-123 on ET-1-induced PRL, TSH, LH, and FSH secretion indicated that BQ-123 has a similar affinity for the receptors mediating ET-1's effects. When BQ-123 was assessed against ET-3, Schild regressions indicated greater affinity for ET-3 on lactotrophs and thyrotrophs than gonadotrophs. Thus changes in pituitary hormone secretion are mediated by ETA-like receptors. ET receptors in lactotrophs and thyrotrophs are clearly distinguishable from gonadotrophs. We suggest the existence of distinct ETA receptor subtypes (ETA1 and ETA2) on these differing pituitary cells.