bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfer of carbon atoms among circulating glucose, alanine, and lactate in pancreatectomized dogs
Authors: Hetenyi G. , Layberry R. A. , Foster D. M. , Berman M.
Published: December 2017

The rates of transfer of carbon atoms (mg C . kg body wt-1 . min-1) among plasma glucose, alanine, and lactate have been calculated in pancreatectomized dogs from the tracer concentration versus time curves in the plasma after an intravenous injection of either [2,3-3H]- and [U-14C]alanine or [3-3H]- and [U-14C]glucose. The calculations were based on an integrated kinetic model derived earlier from experimental data. In comparison to normal dogs, in insulin-deprived pancreatectomized dogs, the rate of turnover of glucose (mg C . kg-1 . min-1) is increased about twofold, but the turnover rates of lactate and alanine are not changed significantly. About twice as much carbon is transferred from lactate to glucose, whereas the transfer of carbon from alanine is increased by 47%. Carbon transfer to glucose from unidentified sources is also doubled. In conclusion, in the pancreatectomized dog, gluconeogenesis is increased not by an increased production of alanine and lactate but by an increased diversion of their carbon atoms to glucose at the expense of other pathways.
ACTH-elicited sodium appetite in sheep
Authors: Weisinger R. S. , Coghlan J. P. , Denton D. A. , Fan J. S. , Hatzikostas S. , McKinley M. J. , Nelson J. F. , Scoggins B. A.
Published: December 2017

Intramuscular injections of long-acting synthetic ACTH (45 U twice daily for 5 days) caused a large increase in the intake of 0.5 M NaCl in sheep. Mean Na intake of the sheep on the last 3 days of treatment approximated 50% of their total extracellular fluid Na. The mineral appetite was specific for NaCl. Intakes of 0.5 M KCl or 0.25 M CaCl2 were not significantly altered. The enhanced appetite for Na induced by ACTH appeared to precede any increase in urinary Na excretion. ACTH treatment was ineffective in adrenalectomized sheep. However, an infusion into adrenalectomized sheep of a combination of adrenal steroid hormones (including aldosterone, deoxycorticosterone, 11-deoxycortisol, cortisol, and corticosterone) that contrived blood levels similar to those, obtained with ACTH treatment in normal sheep did induce Na appetite. Thus, ACTH induces a specific, adrenal-steroid hormone-dependent Na appetite in sheep.
Down-regulation in vivo of PGE receptors and adenylate cyclase stimulation
Authors: Robertson R. P. , Westcott K. R. , Storm D. R. , Rice M. G.
Published: December 2017

Down-regulation in vivo of liver plasma membrane receptors for prostaglandin E (PGE) was investigated in Sprague-Dawley rats using the 16,16-dimethyl analogue of PGE2, This analogue was used for subcutaneous injections because it escapes the rapid pulmonic degradation characteristic of PGE and was recognized well by liver plasma membrane receptors. Following treatment with the analogue, the concentration of PGE receptors was significantly decreased (-37%, P less than 0.001), but the binding affinity was not altered. There was no evidence for carry-through of the analogue into the isolated plasma membrane preparation. It was also demonstrated that GTP decreased the binding affinity between PGE and its receptor. Down-regulation of receptor concentration was associated with a significant decrease (P less than 0.001) in PGE1-stimulated plasma membrane adenylate cyclase activity. These data provide the novel demonstration that rat liver plasma membrane receptor for PGE can be down-regulated in vivo and that this causes a corresponding decrease in PGE-induced plasma membrane adenylate cyclase activity.
Role of Ca2+ in impaired insulin release from islets of diabetic (C57BL/KsJ-db/db) mice
Authors: Siegel E. G. , Wollheim C. B. , Sharp G. W. , Herberg L. , Renold A. E.
Published: December 2017

The involvement of Ca2+ in the impaired insulin release of diabetic C57BL/KsJ-db/db mice was studied. Twenty-week-old severely hyperglycemic mice were compared to nondiabetic C57BL/KsJ mice as controls. Collagenase-isolated islets were maintained for 46 h in tissue culture allowing for equilibration at the same glucose concentration (8.3) mM). The insulin content of both types of islets was similar. In control islets preloaded during culture with 45Ca2+ glucose-induced insulin release was associated with increased 45Ca2+ effux. Islets from diabetic mice showed markedly reduced insulin response to glucose and a smaller increase in 45Ca2+ efflux. Because insulin release was strikingly potentiated by 3-isobutyl-1-methylxanthine (IBMX), even more than in control islets, there was no generalized release defect. In both types of islets, IBMX potentiation was accompanied by a further enhanced 45Ca2+ efflux, possibly suggesting that cAMP effects are associated with increased cytosol Ca2+% concentrations. As Ca2+ uptake was stimulated by glucose in both types of islets, a defect may lie in the mechanism by which glucose uses cellulr calcium to raise cytosol Ca2+ in the beta-cell of these diabetic mice.
Regulation of chondrosarcoma metabolism by cyclic adenosine 3'5'-monophosphate
Authors: McCumbee W. D. , Lebovitz H. E.
Published: December 2017

The in vitro effects of cyclic AMP on amino acid transport and synthesis of macromolecules in the Swarm rat chondrosarcoma were investigated using the cyclic AMP analogue, N6-monobutyryl cyclic AMP (MBcAMP), and the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (MIX). Amino acid transport was assessed by measuring alpha-amino-[1-14C]isobutyrate (AIB) uptake. The synthesis of macromolecules was estimated by measuring radiolabeled precursor incorporation into total proteins, proteoglycan, and RNA. MBcAMP stimulated [14C]AIB uptake, [3H]uridine transport, and UTP formation. MBcAMP inhibited 35SO4 and [3H]leucine incorporation into proteoglycan and stimulated [3H]uridine incorporation into RNA. MIX elevated endogenous cyclic AMP levels in the Swarm rat chondrosarcoma and mimicked the effects of MBcAMP on AIB transport and radiolabeled precursor incorporation into macromolecules. For comparative purposes, the effects of MBcAMP on AIB uptake and macromolecule synthesis in rat costal cartilage segments were investigated. MBcAMP and MIX stimulated AIB uptake by costal cartilage segments, inhibited [3H]leucine incorporation into total protein and 35SO4 incorporation into proteoglycan, and had no effect on [3H]uridine incorporation into RNA.
Increased muscle glucose uptake and lactate release after endotoxin administration
Authors: Romanosky A. J. , Bagby G. J. , Bockman E. L. , Spitzer J. J.
Published: December 2017

Changes in glucose uptake and lactate and alanine release by skeletal muscle were studied in anesthetized dogs before and over a 4-h period after endotoxin administration and in time-matched controls. Blood flow was measured directly, and arteriovenous differences of glucose, lactate, alanine, and O2 were determined in hindlimb muscles by obtaining blood samples simultaneously from the carotid artery and profunda femoris veins. Skeletal muscle blood flow decreased by 29% after endotoxin, reflecting a similar average decrease in cardiac output. Mean arterial glucose decreased 31% and arterial lactate and alanine increased 201 and 123%, respectively, after endotoxin administration. Skeletal muscle glucose uptake increased 57% after endotoxin despite the progressively developing hypoglycemia. Postendotoxin lactate and alanine release were also elevated by 217 and 82%, respectively. Average O2 consumption by skeletal muscle did not change. The metabolic pattern observed after endotoxin administration suggests that the increased lactate and alanine release are likely to be related to the elevated glucose uptake and that skeletal muscle greatly influences the metabolic pattern observed during shock.
Dissociation of apoprotein B and triglyceride production in very-low-density lipoproteins
Authors: Melish J. , Le N. A. , Ginsberg H. , Steinberg D. , Brown W. V.
Published: December 2017

As a first step toward understanding the regulation of apoprotein B (apoB) secretion in man, we have simultaneously studied the production of very-low-density lipoprotein (VLDL) apoB and VLDL triglycerides (TG) in six subjects with plasma TG levels of 153-344 mg/dl, during consumption of control and high-carbohydrate diets. 125I-labeled VLDL and [3H]glycerol were injected intravenously, and blood samples obtained over a 48-h period were used to isolated VLDL 125I-labeled apoB and VLDL 3H-labeled TG. The complex radioactivity curves obtained were analyzed by a multicompartmental model of VLDL metabolism. In accord with previous data, plasma VLDL TG levels were increased in five of six subjects (mean increase of 76% for the group), and in four of the six subjects the VLDL apoB concentrations were increased significantly during the high-carbohydrate period. The estimated rate of secretion of VLDL TG was higher in all six subjects, from 9.4 to 23.5 mg/kg-1 X h-1 on the control diet to 14.0-65.5 mg X kg-1 X h-1 on the carbohydrate diet (P < 0.001). In contrast, there was no increase in the rate of secretion of VLDL apoB in any of the subjects compared to their control period with values ranging from 0.60 to 1.59 mg X kg-1 X h-1 during the control period to 0.63-1.47 mg X kg-1 X h-1 after carbohydrate induction. These results indicate that physiological perturbations of VLDL TG production need not be accompanied by an alteration in VLDL apoB production.
Protein synthesis in perfused rat liver following thyroidectomy and hormone treatment
Authors: Peavy D. E. , Taylor J. M. , Jefferson L. S.
Published: December 2017

Rat livers perfused in situ were used to investigate the effects of thyroid hormone deficiency and subsequent hormone replacement on hepatic protein synthesis and secretion. Following surgical thyroidectomy, production of albumin and total secretory proteins was reduced by 50%, whereas the synthesis of retained intracellular proteins was reduced by only 20% compared to the respective control rates. The 28% reduction in the synthesis of total liver proteins (secreted plus retained) was associated with a fall of similar magnitude in the tissue RNA level. Treatment of thyroidectomized rats with various doses of thyroid hormones indicated a regimen that restored the rate of synthesis of total liver proteins and the concentration of RNA to normal levels. This treatment regimen increased the synthesis of retained proteins to 115% of the control rate, but produced only modest increases in the production of albumin and total secretory proteins. These findings indicated an impairment in protein secretion in livers of thyroidectomized rats that persisted after the defect in protein synthesis was corrected by thyroid hormone treatment.
Adipocyte size and number in dietary obesity resistant and susceptible rats
Authors: Obst B. E. , Schemmel R. A. , Czajka-Narins D. , Merkel R.
Published: December 2017

Fat depot cellularity was assessed in overfed dietary obesity resistant S 5B/Pl (S) and susceptible Osborne-Mendel (OM) rats. Cell number and lipid per cell were determined for three fat depots in both 24- and 105-day-old rats. Between these two ages, fat cell number doubled in inguinal fat depots of S rats fed high- or low-fat diets and OM rats fed a low-fat diet, but quadrupled in OM rats fed a high-fat diet. The size of adipocytes in this depot was influenced by strain but not by diet. Compared to normal weight S rats, 24-day-old overfed S rats had twice as many adipocytes in the perirenal-retroperitoneal fat depot. Overfed OM rats had 3 times perirenal-retroperitoneal fat depot. Overfed OM rats had 3 times as many. In OM rats fed the high-fat diet, there was a 16-fold increase in adipocyte number between 24 and 105 days of age. Overfeeding caused a slight increase in perirenal-retroperitoneal adipocyte size in 24-day-old rats but had little influence on cell size in 105-day-old rats.
Effect of (-)-hydroxycitrate on development of obesity in the Zucker obese rat
Authors: Greenwood M. R. , Cleary M. P. , Gruen R. , Blase D. , Stern J. S. , Triscari J. , Sullivan A. C.
Published: December 2017

Young Zucker lean (Fa/-) and obese (fa/fa) female rats were fed the fatty acid synthesis inhibitor (-)-hydroxy-citrate as a dietary admixture for 39 days. In the lean rats, (-)-hydroxycitrate treatment decreased body weight, food intake, percent of body fat, and fat cell size. In the obese rat, food intake and body weight were reduced but the percent of body fat remained unchanged. Throughout the treatment period, obese rats maintained a fat cell size equivalent to their obese controls. Although a reduction in fat cell number in the obese rats occurred during the treatment period, marked hyperplasia was observed during the posttreatment period. The results of this study indicate that the obese rat, despite a substantial reduction in body weight produced by (-)-hydroxycitrate, still defends its obese body composition.
Hyperinsulinemia and hyperglucagonemia in fasted rats during liver regeneration
Authors: Cornell R. P.
Published: December 2017

The two pancreatic hormones, insulin and glucagon, have been implicated as hepatotrophic factors for the regenerating liver after partial hepatectomy. Similar to previous studies, hyperglucagonemia and hypoinsulinemia were noted following major liver resection of initially well-fed rats. In contrast to well-fed animals, rats fasted for 24 h prior to surgery to deplete hepatic glycogen and establish low basal insulin levels developed both portal venous hyperglucagonemia and hyperinsulinemia after 67% hepatectomy. Elevation of basal portal venous levels of the two hormones suggested enhanced pancreatic secretion of insulin and glucagon in response to acute liver injury in fasted animals. Because polypeptide hormones must bind to specific hepatic cell membrane receptors to exert their hepatotrophic influences, basal portal-systemic venous differences of insulin and glucagon and glucose-elicited portal-hepatic venous insulin differences were evaluated. The evidence implies that hepatic extraction and, therefore, cell membrane receptor binding of both insulin and glucagon by regenerating livers were enhanced even though portal venous levels of the two hormones were elevated.
Human and rat growth hormones enhance guanylate cyclase activity
Authors: Vesely D. L.
Published: December 2017

The objective of this investigation was to determine whether physiological levels of growth hormone have part of their mechanism of action through stimulation of guanylate cyclase (EC 4.6.1.2.). Rat and human growth hormones enhanced the activity of soluble guanylate cyclase two- to fourfold in rat gracilis anticus skeletal muscle, liver, lung, heart, pancreas, and kidney cortex at a concentration of 10 nM. Dose-response relationships revealed that more than half-maximal stimulation of guanylate cyclase activity was seen at a concentration as low as 10 nM and nonstimulation of guanylate cyclase activity was seen when the concentration was decreased to 1 nM. Maximal enhancement was seen at 100 nM of growth hormone, and there was no further enhancement when the concentration was increased to the micromolar or millimolar range. Thus, the data in this investigation indicate that at concentrations at which growth hormone is known to cause its growth-promoting effects, growth hormone does cause an enhancement of the activity of the guanylate cyclase-cyclic GMP system.
Decrease in plasma glucose concentration after microinjection of insulin into VMN
Authors: Iguchi A. , Burleson P. D. , Szabo A. J.
Published: December 2017

The influence of insulin on hypothalamic regulation of blood sugar homeostatis was studied in anesthetized rats. Insulin was injected directly into the ventromedial hypothalamic nucleus (VMN), the lateral hypothalamic area (LHA), the parietal cortex, or the third cerebral ventricle, and changes in hepatic venous plasma glucose concentrations were studied. After injection of 100 microU insulin into the parietal cortex or the third ventricle, hepatic venous plasma glucose concentration did not differ from that of the control rats, which received saline injection into the same CNS regions. Saline injection into the LHA raised the hepatic venous plasma glucose concentration in control rats, where injection of 100 microU insulin into the LHA resulted in a modest but significant decrease of glycemia in the 2-, 5-, and 10-min postinjection samples. As little as 10 microU insulin injected into the VMN eliminated the hyperglycemic response seen in control rats after saline injection into this site. The divergence between insulin-treated rats and their saline-treated controls was further amplified, and an actual fall of plasma glucose was observed in rats given injections of 50 or 100 microU insulin into the VMN. Increasing quantities of insulin (from 10 to 100 microU) injected into the VMN resulted in graded decreases of hepatic venous plasma glucose concentrations, suggestive of a dose-response curve. These observations support the hypothesis that the VMN and the LHA are parts of an insulin-sensitive CNS glucoregulator system that exerts influences on the systemic blood glucose levels by causing rapid alterations in hepatic glucose metabolism.
Effects of amino acids on membrane potential and 86Rb+ fluxes in pancreatic beta-cells
Authors: Henquin J. C. , Meissner H. P.
Published: December 2017

The membrane potential of beta-cells was studied with microelectrodes in mouse islets and their potassium permeability was evaluated by measuring 86Rb+ fluxes in rat islets. In the absence of glucose, L-leucine, its metabolite ketoisocaproate, and its nonmetabolized analogue 2-aminonorbornane-2-carboxylic acid (BCH) depolarized beta-cells and triggered bursts of electrical activity like glucose. The effect of leucine was weak, but was potentiated by a low concentration of glucose or by theophylline; the effect of ketoisocaproate was stronger and faster than that of an equimolar concentration of glucose. Arginine alone produced only a fast depolarization of beta-cells, insufficient to trigger electrical activity. Leucine and arginine potentiated the activity induced by glucose. In a glucose-free medium, alanine only slightly depolarized beta-cells, whereas isoleucine and phenylalanine had no effect. Leucine, ketoisocaproate, and BCH reversibly decreased 86Rb+ efflux from islets perifused in the absence of glucose and increased 86Rb+ uptake. By contrast, both in the absence or presence of glucose, arginine increased 86Rb+ efflux and decreased 86Rb+ uptake. It is proposed that leucine, ketoisocaproate, and BCH, as glucose, depolarize beta-cells by decreasing their potassium permeability, whereas arginine acts differently. The appearance of bursts of electrical activity with secretagogues unrelated to glucose suggests that they reflect an intrinsic property of the beta-cell membrane.
Regulation of pyruvate kinase by 6-phosphogluconate in isolated hepatocytes
Authors: Smith S. B. , Freedland R. A.
Published: December 2017

Isolated liver parenchymal cells from rats fed a 65% sucrose diet for 14 days were incubated in the presence and absence of 10(-6) M glucagon. The pyruvate kinase obtained from homogenates of the glucagon-treated cells displayed and increased Ks 0.5 for phosphoenolpyruvate (P-enolpyruvate), as well as an increased Ka 0.5 for 6-phosphogluconate (6-P-gluconate), compared to pyruvate kinase from untreated cells. Additionally, glucagon treatment decreased the maximal stimulation of pyruvate kinase by 6-P-gluconate by approximately two-thirds and decreased the Hill coefficient value of pyruvate kinase for 6-P-gluconate from 1.76 to 1.56. 6-Aminonicotinamide, an inhibitor of 6-P-gluconate dehydrogenase, increased 6-P-gluconate levels in isolated liver parenchymal cells three- to sevenfold, depending on the substrates present. The flux of P-enolpyruvate through pyruvate kinase was increased from 18 to 40% in these preparations and was highly correlated with the increase in 6-P-gluconate levels. The results suggest that 6-P-gluconate could regulate pyruvate kinase activity in the intact liver parenchymal cell. Furthermore, the activator would be of greatest importance in the lipogenic animal.
Changing activities of galactose-metabolizing enzymes during perfusion of suckling-rat liver
Authors: Rogers S. , Segal S.
Published: December 2017

The specific activities of the galactose-metabolizing enzymes, galactokinase (EC 2.7.1.6), galactose-1-phosphate uridyltransferase (EC 2.7.7.12), and UDPgalactose 4-epimerase (EC 5.1.3.2), in suckling-rat livers perfused for 90 min with 1 and 4 mM galactose fluctuate significantly with a different pattern of change for each enzyme. Perfusion for 30 min with galactose resulted in a significant increase of transferase specific activity followed by a precipitous decline to about one-fifth of the activity in unperfused liver at 90 min. The increase in transferase activity was also observed when D-glucose was perfused but not when L-glucose, D-fructose, D-xylose, or D-ribose was added to the perfusate. No such changes in transferase activity were observed when adult-rat liver was perfused with galactose. Epimerase activity in the suckling-rat liver was relatively low, and the changes in its activity correlated best with the uptake rate of galactose. The perfused suckling-rat liver may provide a model system for examination of factors that modulate the specific activity of galactose-metabolizing enzymes and effect the metabolism of galactose.
Effects of paraventricular lesions on stimulated ACTH release and CRF in stalk-median eminence of the rat
Authors: Makara G. B. , Stark E. , Karteszi M. , Palkovits M. , Rappay G.
Published: December 2017

The effects of destroying the paraventricular nucleus (PVN) of the rat hypothalamus on pituitary-adrenal function were studied. Four days after PVN lesions were placed with a rotating knife, the basal plasma corticosterone level was normal, but the corticosterone response to electrical stimulation of the medial basal hypothalamus, surgical trauma, and ether-venesection stress was significantly inhibited. Four and 8 days after PVN lesioning and adrenalectomy, the basal plasma ACTH level was lower, and the rise of plasma ACTH level elicited by a 3-min ether inhalation was significantly smaller than in the adrenalectomized controls. Corticotropin-releasing factor (CRF) activity in the stalk-median eminence extracts from PVN-lesioned rats was significantly less than in the control extracts. The weight of the adrenals was decreased by both 2 and 4 wk after PVN destruction, and 2 wk after hemiadrenalectomy, the compensatory adrenal hypertrophy was inhibited. The plasma corticosterone response to ether-venesection stress was inhibited only temporarily because it returned to normal by the end of the 4th postoperative week. The results are consistent with the hypothesis that a substantial portion of CRF-containing fibers in the stalk-median eminence region either originate from or run though the PVN or its immediate vicinity.
Corticoliberin activity of rat neurohypophysis is distinct from vasopressin
Authors: Karteszi M. , Stark E. , Rappay G. , Laszlo F. A. , Makara G. B.
Published: December 2017

Electrical stimulation of the neural lobe of the pituitary resulted in an increase of corticosterone secretion in both normal and Brattleboro rats. Bioassaying the corticoliberin (CRF) activity of stalk-median eminence and neural lobe extracts obtained from normal and Brattleboro rats revealed that the endogenous vasopressin was not a prerequisite of ACTH-releasing potency. Arginine-8-vasopressin failed to potentiate the CRF activity of the different extracts. These data suggest that a nonvasopressin substance(s) with CRF activity can be released from the neurohypophysis of the rat, and it may contribute to activating the pituitary-adrenal axis under certain experimental conditions.
Insulin binding, internalization, and receptor regulation in cultured human fibroblasts
Authors: Baldwin D. , Prince M. , Tsai P. , Johnson C. , Lotan R. , Rubenstein A. H. , Olefsky J. M.
Published: December 2017

Insulin binding to receptors was studied using monolayers of cultured normal human fibroblasts. Binding was rapid and inversely related to the incubation temperature; prolonged periods of steady-state binding were achieved at all temperatures studied and the amount of degradation of extracellular insulin was minimal. Competition curves demonstrated half-maximal inhibition of 125I-insulin binding at an unlabeled insulin concentration of 125I-insulin binding at an unlabeled insulin concentration of 7 ng/ml. Scatchard plots of the binding data were curvilinear and revealed that fibroblasts contained about 7,000 receptor sites per cell. Bound 125I-insulin dissociated from fibroblasts with a t 1/2 of 10 min at 30 degrees C and 35 min at 16 degrees C. After 60 min dissociation at 30 degrees C, 45% of the dissociated radioactivity consisted of 125I-insulin degradation products, whereas only 8% of the dissociated material was in the form of degraded products after 60 min of dissociation at 16 degrees C. This indicates that fibroblasts possess a temperature-sensitive receptor-mediated process for insulin degradation. Preincubation of the monolayers with insulin led to a hormone-induced loss of insulin receptors. Thus, incubating cells with 25 ng/ml insulin for 6 h at 37 degrees C caused a 50% reduction in subsequently measured 125I-insulin binding. This hormone-induced receptor loss was sensitive to physiologic insulin levels, with approximately 5 ng/ml causing a half-maximal receptor loss. When monolayers were treated with the lysosomotropic agent chloroquine and subsequently incubated with 5 X 10(-11) M 125I-insulin, a 130% increase in cell-associated radioactivity was observed after 120 min at 30 degrees C. In summary, 1) cultured normal human fibroblasts possess insulin receptors that exhibit kinetic properties and specificity identical to that of other insulin target cells; 2) incubation of fibroblasts with physiologic concentrations of insulin causes a marked loss of cell-surface insulin receptors; and 3) receptor-bound 125I-insulin is internalized through an energy-dependent endocytotic pathway and subsequently degraded by a chloroquine-sensitive reaction.
Vitamin D metabolism in aged Japanese quail: dietary calcium and estrogen effects
Authors: Baksi S. N. , Kenny A. D.
Published: December 2017

The influence of estrogen treatment (estradiol benzoate, 1 mg/kg daily for 5 days) on the in vitro renal metabolism of 25-[3H]hydroxyvitamin D3 has been studied in young adult (8-wk-old) and aged (108-wk-old) female and male Japanese quail maintained either on a normal calcium diet or on a low-calcium diet for 4 wk. It is concluded that senescence leads to reduced production of 1,25-dihydroxyvitamin D2 [1,25(OH)2D3] in untreated birds of both sexes and under both dietary conditions. Nevertheless, the renal vitamin D-endocrine system in aged birds has the capacity, when stimulated under appropriate conditions (estradiol-treated, calcium-deprived aged males), for operating at a very high production rate (315 +/- 21 pmol . min-1 . g kidney-1). The latter rate is not far below the maximal rate (393 +/- 25 pmol . min-1 . g kidney-1) observed in young adult birds that had been stimulated by calcium deprivation.
Effect of exogenous estrogens on catabolism of VLDL in cholesterol-fed rabbits
Authors: Kushwaha R. S. , Hazzard W. R.
Published: December 2017

To determine the metabolic mechanism of the hypolipidemic response to estrogen in cholesterol-fed rabbits, very low-density lipoprotein (VLDL) apolipoprotein B (apoB) turnover studies were conducted in cholesterol-fed animals with or without estrogen treatment. Autologous VLDL apoB had a more rapid fractional catabolic rate (FCR) in estrogen-treated than in untreated animals, but there was no difference in the radioactivity appearing in the intermediate-(IDL) and low- (LDL) density lipoproteins. Similar differences in the FCR were observed when isologous VLDL from donors in the opposite group was injected, suggesting that estrogen treatment in cholesterol-fed rabbits accelerated the catabolism of cholesterol- and apoE-rich lipoproteins by a mechanism that is not dependent on its conversion to LDL. Furthermore, VLDL apoB from normal untreated donor animals was catabolized more rapidly in the estrogen-treated animals, but most of the radioactivity appeared in LDL in both groups. These observations suggest that estrogen treatment of cholesterol-fed rabbits affected only the efficiency but not the completeness of catabolism of normal VLDL. Thus the catabolism of vLDL in cholesterol-fed animals treated with or without estrogen depended on the composition of VLDL injected and the pool size of plasma VLDL, which was reduced by estrogen treatment.
Amino acid supply to individual cerebral structures in awake and anesthetized rats
Authors: Hawkins R. A. , Mans A. M. , Biebuyck J. F.
Published: December 2017

The movement of phenylalanine from plasma into various cerebral structures was examined in detail in normal alert rats as well as in rats anesthetized with nitrous oxide, halothane, and sodium pentobarbital. Radioactive phenylalanine was infused intravenously in such a way as to rapidly establish and maintain a trace concentration in arterial blood. The rat was decapitated after 1.5 min, the brain removed, frozen, and thin sections cut for quantitative autoradiography. The plasma concentrations of phenylalanine as well as other neutral amino acids that compete with phenylalanine for entry into brain were measured. Phenylalanine influx varied considerably between structures, ranging from 5 nmol.min-1.g-1 in the globus pallidus to 12 nmol.min-1.g-1 in the inferior colliculus. Anesthetics reduced phenylalanine influx, but this effect was primarily due to alterations in the circulating neutral amino acid pattern. The anesthetics had little, if any, direct effect on the neutral amino acid transport process itself.
Regulation of calcium-binding protein in mouse placenta and intestine
Authors: Bruns M. E. , Wallshein V. , Bruns D. E.
Published: December 2017

To study the developmental controls for both intestinal and placental calcium-binding protein (CaBP), we have altered mineral metabolism by feeding pregnant mice diets high in calcium and strontium. The effects of these dietary changes on CaBP content of maternal intestine and placenta and also on fetal mineral accumulation have been measured. Feeding high-calcium diets to pregnant mice decreased CaBP content in both maternal intestine and placenta (45 and 58%, respectively). Under these conditions of maternal hypercalcemia, fetal mineral accumulation was unchanged. In experiments with strontium-containing diets, CaBP content was reduced in both maternal intestine and placenta (66 and 67%, respectively), and fetal mineral accumulation was markedly reduced (70%). Administration of 1,25-dihydroxycholecalciferol [1,25(OH)2D] to the strontium-fed mice allowed the gestational rise in maternal intestinal CaBP to proceed to normal levels or above; however, the level of placental CaBP was not affected. Similarly, administration of 1,25(OH)2D to pregnant mice on a normal diet increased maternal intestinal CaBP, but had no effect upon placental CaBP. Thus, administration of 1,25(OH)2D to the mother, in amounts sufficient for a maternal intestinal response, was not a sufficient condition to increase placental production of CaBP.
Ionomycin stimulates secretion of catecholamines from cat adrenal gland and spleen
Authors: Carvalho M. H. , Prat J. C. , Garcia A. G. , Kirpekar S. M.
Published: December 2017

Ionomycin, a polyether antibiotic, stimulated the secretion of catecholamines and dopamine beta-hydroxylase from perfused adrenal glands and [3H]norepinephrine ([3H]NE) from spleens of the cat. Release was calcium dependent, and strontium or barium did not substitute for calcium. Ionomycin failed to release [3H]NE from reserpinized spleens. High magnesium did not interfere in the ionomycin response, but lanthanum and manganese blocked it. Ionomycin response that was pH dependent was not affected by potassium depolarization. The secretory response to ionomycin was enhanced when both glycolysis and oxidative metabolism were inhibited. It is concluded that ionomycin introduces calcium into the chromaffin cells and adrenergic nerve terminals to cause the secretory response and that a rise in intracellular calcium may be an adequate stimulus for secretion.
Electrophysiologic correlates of steroid modulation of luteinizing hormone release
Authors: Leung P. C. , Whitmoyer D. I. , Sawyer C. H.
Published: December 2017

In both ovariectomized (OVX) and steroid-primed OVX freely moving rats, attempts were made to correlate the effects of intraventricular norepinephrine (NE) on multiunit activity (MUA) of different brain regions with NE-induced alterations in blood LH levels. MUA-recording electrodes were implanted in the diagonal band of Broca (DBB), medial preoptic area (MPOA), arcuate nucleus (ARC) and/or ventromedial hypothalamic nucleus (VMH). Steroid priming included 50 micrograms estradiol benzoate (EB) and 25 mg progesterone (P) 3 days prior to experiment. The unanesthetized animals were bled via indwelling atrial cannulas before and after intraventricular infusion of NE (10 micrograms in 2 microliters over 2 min). In OVX-primed rats NE lengthened the interval between episodic LH peaks and decreased mean blood LH levels. In contrast, in OVX-EBP-primed rats, NE stimulated an LH surge. Concurrent recording of MUA revealed that, in OVX-unprimed rats, NE dramatically depressed MUA in both DBB-MPO and ARC-VMH neurons. However, in OVX-EBP-primed rats, while still markedly inhibiting ARC-VMH units, NE failed to depress MUA recorded in DBB-MPO sites (some units were actually excited by NE), perhaps reflecting the higher ratio of LHRH neurons/inhibitory neurons in DBB-MPO.
Autoregulation of rat pituitary prolactin secretion demonstrated by a new perfusion method
Authors: Zacur H. A. , Mitch W. E. , Tyson J. E. , Ostrow P. T. , Foster G. V.
Published: December 2017

Regulation of prolactin secretion was investigated by perfusing rat pituitaries in vitro. Two pituitary glands from inbred rats were transplanted beneath the renal capsule of a third recipient rat. Three weeks later, the transplanted kidney was removed and perfused in vitro with a defined cell-free medium. Normal renal function was maintained during perfusion, and cell morphology of the transplants remained unchanged as assessed by electron microscopy. Pituitary prolactin content did not change after 120 min of perfusion despite release of approximately 10 micrograms of hormone. Thyrotropin-releasing hormone (10 ng/ml) did not stimulate prolactin release; dopamine (20 ng/ml) rapidly, but transiently inhibited prolactin release; bromocriptine (20 ng/ml) rapidly and persistently inhibited prolactin release; haloperidol (100 ng/ml) blocked the inhibition by dopamine or bromocriptine, but when given alone inhibited prolactin release. Finally, prolactin release was also inhibited by the presence of 100 and 200 ng/ml, but not 50 ng/ml of NIAMDD RP-1 rat prolactin. It is concluded that in vitro perfusion of transplanted rat pituitaries provides a new model for studying the direct effect of agents on the secretion of prolactin from the pituitary and that rat prolactin and/or its metabolites directly inhibit pituitary prolactin secretion.
Potassium homeostasis during hyperinsulinemia: effect of insulin level, beta-blockade, and age
Authors: Minaker K. L. , Rowe J. W.
Published: December 2017

The euglycemic glucose clamp technique was used to evaluate the influence of level and duration of hyperinsulinemia, presence of beta-adrenergic blockade, and subject age on insulin-mediated changes in plasma potassium. In 16 young subjects, 2-h insulin infusions at 20 (n = 6), 80 (n = 13), and 200 (n = 8) mU.m-2.min-1 resulted in dose-dependent declines in plasma potassium (P less than 0.001 at all doses) during the 1st h. During the 2nd h plasma potassium declined during the 20 mU.m-2.m-1 infusions, was stable during the 80 mU.m-2.m-1 infusions, and rose slightly during the 200 mU.m-2.min-1 infusions. There was a significant reciprocal relationship between the changes in plasma potassium during the 1st and 2nd h of study (r = 0.99, P less than 0.01). During 4-h infusions (80 mU.m-2.min-1, n = 6) plasma potassium declined during the first 90 min (p less than 0.001) and rose thereafter until the end of the infusion (P less than 0.05). Studies with and without propranolol infusion at two insulin dose levels (20 and 80 mU.m-2.min-1) in six young subjects showed no effect of beta-blockade, and studies at three insulin dose levels [20 (n = 5), 80 (n = 6), and 200 (n = 6) mU.m-2.min-1 in 10 older males (63-77 yr] showed no effect of age on the changes in plasma potassium during hyperinsulinemia. These results suggest the presence of a regulatory mechanism influencing insulin-mediated alterations in plasma potassium. This mechanism appears uninfluenced by age or beta-adrenergic blockade.
Thyroid hormones, malnutrition, and biochemical composition of developing rat lung
Authors: Ruel J. , Coulombe P. , Dussault J. H.
Published: December 2017

We studied the effects of thyroid hormones and malnutrition on protein, DNA, and phospholipid content of the developing rat lung during the first month of life. Neonatal hypothyroidism significantly decreases the lung phospholipid content by 30-45% between 5 and 30 days of age whether the results are expressed per milligram DNA or per gram tissue. Administration of thyroxine for 3 days to hypothyroid rats increases significantly (20%) their total phospholipid content, mainly through its preferential effect on phosphatidylcholine (50% increase). Adult animal response to thyroid hormones is markedly different from that observed in young rats for most parameters examined. In malnourished rats, lung tissue phospholipids are decreased per cell but not per unit cell mass after 11 days of age. These results show that hypothyroidism has a specific effect on lung phospholipids during the neonatal period.
Effect of exercise on rates of oxidation, turnover, and plasma clearance of leucine in human subjects
Authors: Hagg S. A. , Morse E. L. , Adibi S. A.
Published: December 2017

We have previously hypothesized that increased muscle oxidation of leucine in starvation is an adaptive response to fuel deficiency in this tissue. To investigate this hypothesis further, we have measured the rates of oxidation, turnover, and plasma clearance of [1-14C]leucine in six obese subjects at rest and during 2 h of mild leg exercise. This experimental design was based on the fact that exercise has the greatest impact on energy expenditure in muscle, the principal site for leucine oxidation. Exercise produced a fourfold increase in oxygen consumption. The rate of alpha-decarboxylation of leucine was increased twofold by leg exercise, whereas there were modest decreases (13%) in the rates of turnover and plasma clearance of this amino acid. The plasma concentrations of lactate and alanine increased twofold during exercise, but plasma concentrations of leucine and other amino acids, glucose, beta-hydroxybutyrate, and insulin remained unaltered. Our data suggest that during exercise oxidation of leucine as an energy source increases, whereas the utilization of this amino acid as a substrate for protein synthesis decreases.
Steroid hormone receptors and carcinoma of the breast
Authors: McGuire W. L. , Osborne C. K. , Clark G. M. , Knight W. A.
Published: December 2017

The estrogen receptor (ER) assay has become a standard practice in the management of advanced breast cancer. Tumors lacking ER respond infrequently to endocrine therapy, whereas response rates of 50-60% are observed in ER+ tumors. Recent studies indicate that the ER status of the primary tumor is a good predictor of the endocrine dependence of metastatic tumors at the time of subsequent relapse. Furthermore, the absence of ER in the primary tumor is an important independent prognostic indicator of higher rate of recurrence and shorter survival. Quantitative analysis of ER and assay of progesterone receptor (PgR) are useful for increasing the accuracy of selecting patients for hormonal therapy; tumors with a high quantitative ER content or those with a positive PgR display the highest objective response rates. Preliminary analysis suggests that the presence of PgR may be the best available tumor marker of hormone dependence.
Liver glycogen synthase and phosphorylase changes in vivo with hypoxia and anesthetics
Authors: Theen J. , Gilboe D. P. , Nuttall F. Q.
Published: December 2017

Methods for obtaining and processing rat liver for determination of glycogen phosphorylase a and synthase I activity were studied. An extremely rapid and profound increase in phosphorylase was induced by hypoxia. The effect on synthase I was slower and less striking. Using alpha- and beta-adrenergic antagonists, a catecholamine-depleting agent, and a ganglionic blocking agent, it was determined that adrenergic stimulation secondary to the surgical procedure required to obtain the liver was not a significant factor. The anesthetic agent used also had a significant effect on the proportion of phosphorylase in the a form. Seconal anesthesia resulted in lower phosphorylase a levels than did ether or urethan anesthesia.
Effects of stimulation of renin release on trypsin-activable renin in rat plasma
Authors: Barrett J. D. , Eggena P. , Sowers J. R. , Sambhi M. P.
Published: December 2017

Little information is available concerning inactive renin in rat plasma. A renin assay method has now been developed for measurement of active and inactive renin in approximately 0.1 ml rat plasma. Trypsin treatment of plasma (5.0 mg trypsin/ml plasma for 5 min at 0 degrees C) to maximally increase the rate of angiotensin I generation did not alter the Km or pH optimum of the renin reaction. Utilizing trypsin, 79 +/- 6% of the total renin (active + inactive) in normal rat plasma is in the inactive form. In vivo stimulation of renin by restraint stress induces a reciprocal change in active and inactive plasma plasma renin, and exposure of animals to ether elevates active and total renin, whereas inactive renin shows a small but nonstatistical decline. Although a parallel disappearance of active and inactive renin is observed after bilateral nephrectomy of the pentobarbital-anesthetized animal, complete occlusion of the renal arteries and veins after ether-induced renin stimulation results in a significant increase of inactive renin. This suggests that possibility of formation of inactive renin from the active enzyme in high renin states. These studies indicate that the balance of active and trypsin-activable renins in rat plasma may be dependent or not only the method but also the degree of in vivo renin stimulation.
Increased fetal insulin receptors and changes in membrane fluidity and lipid composition
Authors: Neufeld N. D. , Corbo L.
Published: December 2017

Fetal tissues exposed to hyperinsulinemia in utero have significantly greater numbers of insulin receptors than do those of controls. We have studied this upregulation phenomenon using crude microsomal membranes from fetal rabbit litters exposed to varying degrees of hyperinsulinemia in diabetic pregnant rabbits. We have observed that insulin binding capacity of membranes increased directly with the severity of maternal diabetes, ranging from 8.5 ng in controls to 44.6 ng insulin/mg membrane protein in offspring of severely diabetic animals and related directly with increasing fetal insulin levels (r = 0.77, P less than 0.005). Lipid analyses of fetal lung membranes showed that reduction of phospholipid to protein ratios occurred in the presence of maternal diabetes. Membrane cholesterol-to-phospholipid ratios were also altered in the presence of maternal diabetes. Significantly, increases in plasma membrane microviscosity were noted in the membranes from diabetic offspring. The data suggest that reduction of membrane fluidity is associated with increases in fetal membrane insulin receptors in severely diabetic pregnancies.
Inhibition of 25-hydroxyvitamin D3-1-hydroxylase by chronic metabolic acidosis
Authors: Reddy G. S. , Jones G. , Kooh S. W. , Fraser D.
Published: December 2017

Chronic metabolic acidosis had been shown to influence the renal metabolism of 25-hydroxyvitamin D3. Using the isolated perfused rat kidney model, we evaluated the rates of synthesis of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in vitamin D-depleted [D(-)] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] in vitamin D-replete [D(+)] rats. Metabolic acidosis was induced in both groups of rats by feeding aqueous ammonium chloride for 9 days. Kidneys isolated from D(-) acidotic rats (mean pH, 7.11) exhibited a decreased rate of 1,25(OH)2D3 synthesis (0.79 +/- 0.17 pmol produce . h-1 . g kidney-1) when compared with that (1.27 +/- 0.09) of D(-) nonacidotic (mean pH, 7.33) rats. There was a significant negative linear correlation between the rate of synthesis of 1,25(OH)2D3 and the hydrogen ion concentration of the animal (r = 0.79, P less than 0.005). The rate of synthesis of 24,25(OH)2D3 by the kidneys from D(+) acidotic (mean pH, 7.06) and nonacidotic (mean pH, 7.39) rats did not differ (0.81 +/- 0.21 vs. 0.60 +/- 0.12 pmol product . h-1 . g kidney-1). It is concluded that chronic acidosis suppressed 1-hydroxylase activity, but does not suppress 24-hydroxylase activity.
Hormonal and hemodynamic responses to vena caval obstruction in fetal sheep
Authors: Wood C. E. , Keil L. C. , Rudolph A. M.
Published: December 2017

To test the hypothesis that ACTH and vasopressin responses are quantifiable as functions of induced changes in central venous or arterial pressures, we produced various degrees of vena caval obstruction in fetal sheep (118--134 days gestation). In seven experiments, vena caval obstruction increased heart rate 18 +/- 7 beats/min and carotid arterial oxygen saturation 8.4 +/- 2.1%, but did not alter any measured vascular pressure or hormones. More severe vena caval obstruction (n = 10) decreased mean arterial pressure 13 +/- 2 mmHg, central venous pressure 1.3 +/- 0.3 mmHg, and heart rate 47 +/- 12 beats/min, and increased fetal plasma ACTH 1,047 +/- 448 pg/ml, cortisol 4.4 +/- 2.2 ng/ml, and vasopressin 47.9 +/- 24.2 pg/ml, but did not alter 11-deoxycortisol. The stimulus increased plasma cortisol (radioimmunoassay after chromatography) 100% and "corticosteroids" (radiotransinassay without chromatography) 20%, demonstrating the nonlinear relationship between these two variables. End-inflation plasma ACTH and vasopressin concentrations were significantly related to the induced decreases in mean arterial and central venous pressures, suggesting that the hormonal responses to vena caval obstruction were mediated by cardiovascular mechanoreceptors. Plasma vasopressin concentrations were linearly related to plasma ACTH concentrations (4 = 0.94; P less than 0.001), suggesting parallel release of the two hormones.