bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of calcium fluxes in pancreatic islets: glucose-induced calcium-calcium exchange
Authors: Herchuelz A. , Couturier E. , Malaisse W. J.
Published: December 2017

Glucose provokes an initial fall followed by a secondary rise in 45Ca efflux from prelabeled pancreatic islets. Prior exposure of the islets to calcium-depleted media does not suppress the secondary rise, provided that the extracellular calcium concentration is normalized 2 min before addition of glucose. Such a treatment significantly reduces insulin release. The secondary rise, as distinct from the initial fall, is inhibited under conditions known to interfere with calcium entry into the beta-cell, e.g., in the presence of ruthenium red or cobalt. Calcium itself in high concentrations provokes a dramatic increase in 45Ca efflux. The magnitude of this calcium-induced efflux is enhanced by prior exposure of the islets to calcium-depleted media. Imidazole and the theophylline do not modify the effect of glucose on 45Ca efflux. It is proposed that the glucose-induced secondary rise in 45Ca efflux corresponds to a calcium-calcium exchange process in which influent 40Ca displaces 45Ca from intracellular sites.
Food restriction as a modulator of age-related changes in serum lipids
Authors: Liepa G. U. , Masoro E. J. , Bertrand H. A. , Yu B. P.
Published: December 2017

Fischer 344 male rats were either fed ad libitum or 60% of the ad libitum intake. The restriction of food intake markedly increased the median length of life. Postabsorptive serum cholesterol and phospholipid concentrations increase in the ad libitum-fed rats with increasing age. Life-prolonging food restriction does not influence the serum levels of these lipids in young rats but delays the age-related increase in concentrations. Postabsorptive serum free fatty acid (FFA) concentrations decrease with advancing age in ad libitum-fed rats. Life-prolonging food restriction, while not affecting the serum FFA levels in young rats, delays and possibly partially prevents the age-related decrease in concentration. Food restriction lowers postabsorptive serum triglyceride levels at all ages studied. The data on serum cholesterol, phospholipids, and FFA provide further evidence that food restriction delays age-related changes in the physiological systems of rats. This delay of physiological decline may well retard the occurrence of age-related disease processes, thus prolonging life.
Food and protein intake, glucagon, and distribution of alpha-aminoisobutyrate in the rat
Authors: Tews J. K. , Harper A. E.
Published: December 2017

Distribution of alpha-aminoisobutyric acid (AIB) in the rat was modified by food, dietary protein, and glucagon. In rats last fed 24 h before AIB injection, AIB clearance from plasma and uptake into liver were greater in rats fed a high-protein diet (60% casein) than in rats fed the control diet (18% casein); AIB clearance from plasma and uptake into muscle were lowered by a low-protein diet (6% casein). Feeding rats lowered clearance of AIB from plasma in low- and high-protein groups. Distribution ratios (AIB concentration in tissue water/AIB in plasma) were low in all tissues but liver during the first 7 h after feeding high protein when compared to the control values; ratios were low in muscle, heart, and kidney after feeding low protein. Maximum ratios occurred at different times for different tissues; the time was delayed by the high-protein diet in all tissues but liver. Glucagon increased all ratios in rats fed the control or low-protein diets, with the smallest changes occurring in liver and muscle from low-protein rats.
Measurement of leucine metabolism in man from a primed, continuous infusion of L-[1-3C]leucine
Authors: Matthews D. E. , Motil K. J. , Rohrbaugh D. K. , Burke J. F. , Young V. R. , Bier D. M.
Published: December 2017

Leucine metabolism in vivo can be determined from a primed, continuous infusion of L-[1-13C]leucine by measuring, at isotopic steady state, plasm [-13C]leucine enrichment, expired 13CO2 enrichment, and CO2 production rate. With an appropriate priming dose of L-[1-13C]leucine and NaH13CO3, isotopic steady state is reached in less than 2 h, and the infusion is completed in 4 h. The method can determine rates of leucine turnover, oxidation, and incorporation into protein with typical relative uncertainties of 2, 10, and 4%, respectively. The method requires no more than 1 ml of blood and uses stable isotope rather than radioisotope techniques. Thus, the method is applicable to studies of human beings of all ages. L-[1-13C]leucine may be infused with a second amino acid labeled with 15N for simultaneous determination of the kinetics of two amino acids.
Growth hormone 3.6-h pulsatile secretion and feeding times have similar periods in rats
Authors: Richter C. P.
Published: December 2017

In rats, lengths of cycles of growth hormone secretion and of cycles of feeding are 3,6-4.0 h. The two may be controlled by the same timing mechanism.
Mechanism of hyperinsulinemia in endotoxicosis
Authors: Yelich M. R. , Filkins J. P.
Published: December 2017

Hyperinsulinemia subsequent to endotoxemia is a key factor leading to the disturbance of glucose homeostasis in endotoxin shock. This study investigated the mechanism(s) of hyperinsulinemia during endotoxicosis in the rat. Two primary mechanisms for the hyperinsulinemia were evaluted: 1) decreased removal of insulin by the endotoxic liver, and 2) increased secretion of insulin by the endotoxic pancreas. Endotoxin treatment of donor rats did not impair the removal of TCA-precipitable 125I-labeled insulin by the isolated perfused liver. Perfused pancreases from endotoxic donors secreted more insulin tha control pancreases in response to a provocative stimulus of glucose. In vivo measurements of plasma immunoreactive insulin and glucose indicated an elevated hepatic portal vein insulin:glucose ratio associated with endotoxicosis. Therefore, the hyperinsulinemia of endotoxicosis is due primarily to hypersecretion of insulin by the endotoxic pancreas.
Perinatal parathyroid hormone, vitamin D metabolites, and calcitonin in man
Authors: Wieland P. , Fischer J. A. , Trechsel U. , Roth H. R. , Vetter K. , Schneider H. , Huch A.
Published: December 2017

Plasma levels of calcium and of parathyroid hormone (PTH) were comparable in the mothers at delivery and in nonpregnant controls; magnesium was decreased (P < 0.001) in maternal blood; and phosphate (P < 0.001), 1,25-dihydroxyvitamin D (1,25(OH)2D) (P < 0.001), and calcitonin (CT) (P < 0.01) were raised. Cord levels of calcium (P < 0.01), magnesium (P < 0.05), and CT (P < 0.01) were higher, and PTH (P < 0.01) was lower than in the maternal blood. Levels of 25(OH)D, 1,25(OH)2D, and 24,25(OH)2D lower in fetal than in maternal blood (P < 0.01) and significant linear correlations between the vitamin D metabolites examined in mothers and neonates (P < 0.001) are consistent with a diffusion barrier across the placenta and/or different affinities of binding proteins. Plasma levels of 25(OH)D and 24,25(OH)2D were significantly related (P < 0.01), suggesting precursor product type, relationships. Levels of 1,25(OH)2D higher in arterial than in venous umbilical blood (P = 0.06, sign test; P < 0.005, paired t test) suggest that the fetus participates in the synthesis of 1,25(OH)2D. Maternal PTH was significantly related to the arteriovenous difference of 1,25(OH)2D levels (P < 0.01) in cord blood, and it possibly enhances the synthesis of 1,25(OH)2D during the final stage of fetal development.
Hypothalamic obesity in female rats in absence of vagally mediated hyperinsulinemia
Authors: King B. M. , Phelps G. R. , Frohman L. A.
Published: December 2017

In order to assess the role of vagally mediated hyperinsulinemia in hypothalamic obesity, plasma insulin and glucose levels were assayed in vagotomized and sham-vagotomized female rats after a 6-h fast and after a measured glucose meal both before and 10–14 days after ventromedial hypothalamic (VMH) lesions. Both groups displayed similar gains in body weight in the first 10 days after VMH lesions, but only the sham-vagotomized VMH-lesioned animals displayed elevated fasting insulin levels. Fasting glucose levels did not differ either before or after the lesion. The insulin response to oral glucose was increased in VMH rats, both in vagotomized and sham-vagotomized animals, and it is concluded that the hyperresponsiveness to oral glucose is independent of vagal mediation. Vagotomy markedly exaggerated the glucose and insulin response to oral glucose loading in both intact rats and rats with VMH lesions, probably as a result of more rapid absorption of glucose from the intestine. It is concluded that the fasting hyperinsulinemia that is characteristic of VMH animals is under vagal control and that its elimination does not prevent the development of obesity.
Elevations in plasma ADH levels during PEEP ventilation in the dog: mechanisms involved
Authors: Bark H. , Le Roith D. , Nyska M. , Glick S. M.
Published: December 2017

In an attempt to define more precisely the various mechanisms involved in antidiuretic hormone (ADH) release during positive end-expiratory pressure ventilation (PEEP), experiments were performed on seven groups of dogs. PEEP-10 and PEEP-15 cmH2O caused significant elevations of plasma ADH from basal values of 24.9 +/- 5.2 pg/ml (mean +/- SE) to 64.6 +/- 14.2 and 106.0 +/- 20.6, respectively (P < 0.02, P < 0.005). The ADH levels returned to basal values after cessation of PEEP. This rise in ADH levels was prevented by an infusion of dextran prior to PEEP. The fall in blood pressure and cardiac output that occurred during PEEP was also prevented by the dextran infusion. Changes in ADH levels were unrelated to lung volume, left transmural pressure, and serum osmolality. Bilateral vagotomy and carotid sinus denervation was followed by an attenuated rise in ADH levels in terms of the percent rise above base line, but it did not significantly alter the absolute rise in ADH during PEEP. ADH levels were, however, reduced significantly by decreasing intracranial pressure by the removal of cerebrospinal fluid during PEEP. Propranolol administration prior to PEEP completely blocked plasma renin activity. Although the peak ADH levels were unaffected by propranolol, the rise was delayed. The results obtained indicate that a number of physiological factors may affect plasma ADH levels during PEEP. These include the carotid body and aortic arch baroreceptors as wells as sensors of intracranial pressure.
Brain metabolism after 30 minutes of hypoxic or anoxic perfusion or ischemia
Authors: Kintner D. , Costello D. J. , Levin A. B. , Gilboe D. D.
Published: December 2017

In 48 separate experiments, isolated canine brain preparations were subjected to 30 min of either hypoxic (PaO2 congruent to 20 mmHg) perfusion, anoxic (PaO2 < 10 mmHg) perfusion, or total ischemia followed by reperfusion for up to 2 h with normal oxygenated blood. Unlike ischemia and anoxia, energy metabolism was sufficient during hypoxia to maintain substantial levels of ATP (48% of normal), sustain normal ion gradients, and prevent edema formation. Posthypoxia metabolism was adequate to clear accumulated lactate, enable recovery of normal tissue glucose levels, and allow return to normal levels of glycolytic intermediates. Although not as complete as that following hypoxia, recovery from cerebral edema and restoration of metabolism were better in ischemic than anoxic cortex. The reduced oxygen uptake in all groups during reoxygenation (55% of normal) indicates that all have a diminished capacity for energy metabolism. The ATP levels recovered more rapidly after 15 min of reoxygenation in the anoxic (57% of normal) than in the ischemic (21% of normal) group. Thus ATP does not appear to be directly related to recovery from edema.
[U-14C]glucose, -alanine, and -leucine oxidation in rats at rest and two intensities of running
Authors: White T. P. , Brooks G. A.
Published: December 2017

The oxidations of injected [U-14C]glucose, [U-14C]alanine, and [U-14C]leucine were investigated in laboratory rats during rest or 2 h of easy and hard treadmill running. After [U-14C]glucose injection, the rate and magnitude of 14CO2 evolution were relatively low at rest and increased as a linear function of metabolic rate (VO2). Evolution of 14CO2 after [U-14C]alanine injection was faster and larger during exercise than rest. The peak of alanine decarboxylation occurred before glucose and, therefore, did not reflect conversion of alanine to glucose prior to decarboxylation. The rate and magnitude of 14CO2 evolution after [U-14C]leucine injection were proportional to metabolic rate, but less than after glucose or alanine injection. During exercise, levels of alanine and leucine in muscle and blood were unchanged or elevated compared to rest. During exercise, alanine levels were unchanged or increased in liver. Liver leucine levels were depressed when exercise began, but increased toward control values during exercise. The metabolism of selected amino acids is joined to carbon flow sustaining exercise.
Specific FSH suppression in male rat by porcine follicular fluid
Authors: Lorenzen J. R. , Dworkin G. H. , Schwartz N. B.
Published: December 2017

A variety of protocols using intact, castrated, and sham-castrated adult male rats was used to test the ability of porcine follicular fluid to selectively suppress serum follicle-stimulating hormone (FSH). A total dose of 500 microliters follicular fluid injected intraperitoneally will suppress FSH in the rat with testes within 5 h of injection. This is more than is necessary to suppress FSH in the intact or ovariectomized female. A total dose of 1 ml of follicular fluid is needed to suppress FSH reliably in the castrated male rat. Serum FSH is suppressed significantly beginning between 4 and 5.5 h after intraperitoneal injection of 1 ml of follicular fluid and 3 h after intravenous injection. The suppression continues until 10 h postinjection and is abated by 26 h postinjection. Serum luteinizing hormone (LH) is unaffected by follicular fluid in any protocol tested. It is concluded that 1) follicular fluid can suppress serum FSH in the male if large enough doses are given, 2) follicular fluid has no effect on serum LH, and 3) follicular fluid suppresses serum FSH levels in the male as well as previously tried testicular sources. These results suggest that the delay in demonstrating the existence of inhibin may be due to the use of males as both source and test subject.
Effects of hyperosmolarity on basal and insulin-stimulated muscle sugar transport
Authors: Forsayeth J. , Gould M. K.
Published: December 2017

Xylose uptake was stimulated rapidly when rat soleus muscles were incubated in Krebs-bicarbonate medium made hyperosmolar by the addition of 200 mM mannitol. The stimulatory effect of hyperosmolarity increased as the concentration of mannitol was raised from 50 to 200 mM; above 200 mM, the effect tended to decline. Mannitol stimulated sugar transport submaximally compared with the effect of insulin. The stimulatory effect of hyperosmolarity persisted over a 60-min incubation period, but could be reversed by transferring the muscles to an isotonic incubation medium. Xylose uptake measured in the presence of insulin (0.1 U/ml) was depressed when muscles were exposed to concentrations of mannitol greater than 100 mM. This effect was not reversible; xylose uptake remained depressed when these muscles were transferred to an isotonic medium. Hyperosmolarity also depressed the binding of 125I-insulin irreversibly. These inhibitory effects of hyperosmolarity were associated with the lowering of muscle ATP. This effect on ATP provides an explanation for the inhibitory effects of hyperosmolarity on insulin-stimulated sugar transport and on insulin binding, in terms of the ATP-dependence of these two processes.
Relationship between endogenous 3-methylhistidine excretion and body composition
Authors: Lukaski H. C. , Mendez J. , Buskirk E. R. , Cohn S. H.
Published: December 2017

Fourteen healthy men (aged 20-30 yr) consumed two isocaloric, isonitrogenous diets in the sequence of a 4-day meat diet (MD) followed by a 7-day meal-free diet (MFD). Urinary 3-methylhistidine (3MH) excretion during the MD (513 +/- 21 mumol . day-1, mean +/- SE) was significantly higher (P less than 0.01) than day 3 of the MFD (230 +/- 10 mumol . day-1), after which the mean daily 3MH output was constant with a mean coefficient of variation of 4.5%. There was no change in fat-free body mass (FFBM) determined by densitometry at the start (62.3 +/- 1.8 kg) and the end (62.2 +/- 1.9 kg) of the 11-day dietary period. Mean muscle mass (MM) calculated from measurements of total-body potassium and nitrogen was 23.4 +/- 1.3 kg. Endogenous 3MH excretion was related more closely to MM (r = 0.91, P less than 0.001) than to FFBM measured by densitometry (r = 0.81, P less than 0.001). Only a low correlation coefficient (r = 0.33, P less than 0.05) was observed between 3MH and the nonmuscle component of FFBM. Urinary creatinine output also was correlated significantly with 3MH (r = 0.87; P less than 0.001) and MM (r = 0.79; P less than 0.01). It is concluded that because endogenous 3MH is significantly related to MM in man, it can be used as a marker to study in vivo total-body muscle protein degradation provided that the necessary dietary restrictions are observed.
Circadian corticosterone rhythm and stress response in rats with adrenal autotransplants
Authors: Gibson M. J. , Krieger D. T.
Published: December 2017

A significant circadian variation in plasma corticosterone concentrations as determined by sequential sampling was observed in rats with adrenals autotransplanted (ADT) to the inguinal region as well as in sham-operated controls when studied 3 wk after surgery. Phase shifting of plasma corticosterone concentrations was observed in a second ADT group placed in reverse photoperiod (D12:L12, lights on 1900) for 2 wk. Intravenous injections of ACTH in dexamethasone-suppressed animals resulted in significant increments in plasma corticosterone concentrations in sham-operated but not in ADT animals. ADT and sham groups both showed elevated plasma corticosterone concentrations after ether or 30-min immobilization stress, although greater responses were present in the sham group. It appears that direct innervation of the adrenal is unnecessary for the maintenance of circadian plasma corticosterone concentrations or certain stress responses.
Intestinal phosphate transport and alkaline phosphatase activity in the chick
Authors: Birge S. J. , Avioli R. C.
Published: December 2017

The initial rates of phosphate accumulation by isolated chick intestinal epithelial cells have been examined. At high concentrations of phosphate (1.5 mM), phosphate uptake is relatively independent of sodium and demonstrates a pH optimum of 8.0. At pH 8.0, 56% of the uptake is dependent on the presence of Ca in the uptake medium compared to 28% at pH 6.8. Membranes prepared from these same intestinal epithelial cells contain a Ca-dependent phosphatase that can be distinguished from the more abundant Mg-dependent alkaline phosphatase. The Ca-dependent phosphatase has a pH optimum between 8.5 and 9.0 and, compared to the Mg-dependent activity, is more readily inactivated at 58 degrees C and is relatively resistant to L-phenylalanine inhibition but more sensitive to ethane-1-hydroxy-1,1-diphosphonate (EHDP). Both activities are distributed in a constant proportion between the brush border and basal lateral membranes and at various segments along the intestine. Vitamin D in vivo and 25-hydroxyvitamin D [25(OH)D] in vitro stimulated both activities. In vitro, utilizing the isolated intestinal cells, the stimulation of phosphate uptake paralleled the increase in Ca-dependent alkaline phosphatase activity. The role of alkaline phosphatase in intestinal phosphate transport is discussed.
Effects of diabetes and fasting on pantothenic acid metabolism in rats
Authors: Reibel D. K. , Wyse B. W. , Berkich D. A. , Palko W. M. , Neely J. R.
Published: December 2017

The effects of fasting and diabetes on pantothenic acid (PA) metabolism were studied in rats. Tissue levels of PA and coenzyme A (CoA) and rates of [14C]PA uptake and incorporation into tissue CoA were determined. Both fasting and diabetes resulted in accelerated rates of [14C]PA uptake, higher tissue concentrations of PA, increased incorporation of [14C]PA into CoA, and elevated tissue concentrations of CoA in the liver. The concentration of PA in liver was near the Km of pantothenate kinase for PA in control animals, and increased PA uptake may, in part, account for the increased [14C]PA incorporation into CoA though an elevation in tissue PA levels. In cardiac muscle, increased [14C]PA incorporation into CoA and increased CoA levels were associated with reduced PA uptake and reduced tissue PA levels in both fasting and diabetic animals, suggesting that CoA synthesis is not controlled by substrate availability in this tissue. Uptake of [14C]PA by skeletal muscle was also reduced in diabetic animals. These data suggest that PA uptake by tissues is under metabolic or hormonal control. Decreased uptake by muscle and increased uptake by liver may represent a mechanism for shifting large body stores of PA present in muscle to the liver in which endogenous PA concentrations are normally low. In addition, both fasting and diabetes resulted in decreased urinary PA excretion, a finding that may represent a regulatory mechanism to conserve whole-body PA under these conditions.
Ontogeny of endocrine (ACTH, vasopressin, cortisol) responses to hypotension in lamb fetuses
Authors: Rose J. C. , Meis P. J. , Morris M.
Published: December 2017

We studied the ACTH, vasopressin (AVP), and cortisol responses to nitroprusside-induced hypotension in 27 chronically cannulated lamb fetuses between 0.53 and 0.98 gestation. Age-related differences in the hormonal responses to hypotension were found. Hypotension was associated with peak AVP levels of 7.8 +/- 2.7 pg/ml (mean +/- SE) in animals less than 0.68 gestation and 63.5 +/- 20 pg/ml in animals 0.89–0.98 gestation (P less than 0.05). The peak ACTH response was 95 +/- 20 pg/ml in the youngest animals and 380 +/- 111 pg/ml in animals 0.83–0.88 gestation (P less than 0.05). These observations suggest that maturation of the systems (possibly neuroendocrine) subserving the hormonal responses occurs in utero. Fetal plasma cortisol levels did not increase in response to the increase in ACTH except in animals 0.89–0.98 gestation. At this time, the basal plasma cortisol levels were high (58.8 +/- 16.8 pg/ml) and the ACTH response to hypotension was attenuated. Taken together, these findings suggest functional negative feedback regulation of ACTH by cortisol in the late gestation fetus.
Effect of changing dietary fat saturation on low-density lipoprotein metabolism in man
Authors: Turner J. D. , Le N. A. , Brown W. V.
Published: December 2017

The mechanism of change in low-density lipoprotein (LDL) levels by diets differing in fat saturation have been studied. Turnover of 125I-LDL was measured in eight subjects with type II hyperlipoproteinemia and in seven normal control subjects during two dietary periods containing 40% of calories as either safflower oil (polyunsaturated fat, PSF) or as lard (saturated fat, SF). Higher levels of LDL apoprotein and LDL-cholesterol were observed in both groups on saturated fat. Subjects with elevated LDL levels (type II) showed a more marked effect of polyunsaturated fat with 25% lower LDL production rate as compared to a reduction of only 10% for the control group. On the PSF diet, the production rate in type II (12.7 mg.kg-1.day-1) was not statistically different from normal subjects (10.5 mg.kg-1.day-1). On this diet, the higher levels of LDL cholesterol in the type II subjects (as compared to controls) were due to a lower fractional clearance rate, mean of 0.27/day compared to a mean of 0.39/day for the normal subjects. Although individuals with type II hyperlipoproteinemia may have a primary clearance defect, the major reduction in plasma cholesterol concentrations achieved with a diet high in polyunsaturated fat can be attributed to a significantly lower LDL production.
Proteolysis in the rat lung: hypoxia and evidence for an inhibitor of proteolysis
Authors: Chiang M. J. , Kishi F. , Whitney P. , Massaro D.
Published: December 2017

We labeled proteins with [14C]phenylalanine in rats breathing air and assessed the rate of proteolysis in the isolated ventilated lung by measuring the accumulation of [14C]phenylalanine in the medium perfusing the lung. Ventilation with 0% O2 decreased the rate of proteolysis and the ATP content in the lung 60%. Medium from lungs ventilated with 0% O2, when used to perfuse lungs ventilated with 95% O2, decreased the rate of proteolysis 60% without lowering the ATP content of the lung. Correcting the pH of "used" medium or dialyzing used medium did not decrease its ability to inhibit proteolysis. Used medium from nonhypoxic lungs, or exogenous lactate (50 mM), diminished proteolysis only 20%. In a cell-free system the degradation by cathepsin D of radioactive lung proteins and radioactive hemoglobin was decreased by used medium from hypoxic lungs. We conclude that the hypoxic perfused lung releases a factor(s) that decreases the rate of proteolysis in nonhypoxic lungs and that this factor may be a protease inhibitor.
Somatostatin, insulin, and glucagon secretion from isolated perfused pancreas of obese rats
Authors: Seino S. , Seino Y. , Takemura J. , Tsuda K. , Kuzuya H. , Ishikawa K. , Shimazu T. , Imura H.
Published: December 2017

A comparison of the somatostatin with the insulin and glucagon secretions in hypothalamic obesity and genetic obesity was made using the isolated perfused pancreas of rats. In our perfusion experiment, the somatostatin response to 19 mM arginine in the presence of 4.4 mM glucose was significantly greater in both ventromedial hypothalamus (VMH)-lesioned and Zucker fa/fa rats than in their controls, as was the perfusate insulin. The perfusate arginine-stimulated glucagon secretion appeared no different in obese and control rats. Because hyperinsulinemia in vivo and hyperresponses to arginine of perfusate insulin and somatostatin were observed in both VMH-lesioned and Zucker fa/fa rats, whereas the perfusate glucagon secretion in the presence of 4.4 mM glucose was unchanged by obesity, the secretory behavior of some pancreatic hormones seems similar in VMH-lesioned and Zucker fa/fa rats in certain conditions. These results suggest that some abnormalities of pancreatic hormone secretion may be caused by a mechanism common to obesity, whether caused experimentally or genetically.
Muscle glycogenolysis during exercise: dual control by epinephrine and contractions
Authors: Richter E. A. , Ruderman N. B. , Gavras H. , Belur E. R. , Galbo H.
Published: December 2017

The interaction of epinephrine and contractions on muscle metabolism was studied in the isolated perfused rat hindquarter. Subtetanic contractions (180/min) through 20 min elicited glycogenolysis and increased phosphorylase a activity. In the soleus, a slow-twitch red muscle, these effects were transient, but when epinephrine at a physiological concentration (2.4 X 10(-8) M) was added to the perfusate, glycogenolysis and phosphorylase activity were sustained throughout contractions. At this high frequency of contractions, the effect of epinephrine was much smaller in the fast-twitch red fibers and not significant in the fast-twitch white fibers of the gastrocnemius muscle. However, during less frequent contractions (30/min) epinephrine increased glycogenolysis and phosphorylase a activity in fast-twitch muscle. The data suggest that epinephrine and muscle contractions exert a dual control of muscle glycogenolysis during exercise: contractions principally stimulate glycogenolysis early in exercise, and a direct effect of epinephrine on muscle is needed for continued glycogenolysis. In addition, epinephrine increased oxygen consumption and glucose uptake in both resting and electrically stimulated hindquarters and, under some conditions, it had a positive inotropic effect on contracting muscle.
Cold acclimation in insulin secretion of isolated perfused pancreas of the rat
Authors: Harada E. , Habara Y. , Kanno T.
Published: December 2017

The secretory function of the endocrine and exocrine pancreas in the process of cold acclimation has been studied in rats fed at an ambient temperature of 2 degrees C. In anesthetized rats, plasma glucose decreased immediately after cold exposure and increased again toward the basal level after 20 days of continuous cold exposure. Plasma insulin level in these rats also decreased immediately after cold exposure, and the low level was maintained throughout the whole period of cold exposure. In the isolated perfused rat pancreas, the basal insulin output estimated before the stimulation with glucose decreased immediately after the cold exposure and increased gradually during the continuous cold exposure. In these preparations, the initial and the second phases of insulin output were induced by sustaining stimulation with 16.7 mM glucose. Changes in the glucose-induced initial and second phases showed a diphasic pattern during the course of cold exposure. Thus, there was temporary decrease within a week of cold exposure followed by a gradual increase after 3 wk of this condition. The diphasic insulin output in the preparation isolated from rats fed during cold exposure for 6 wk was twice as much as that in the preparation isolated from the rats fed during exposure to 23 degrees C for 5 wk. In the isolated perfused rat pancreas, a monophasic insulin output was induced by sustaining stimulation with 0.1 microM ACh. The monophasic insulin output showed an increasing tendency during cold exposure, but the increase was insignificant because of a larger individual variation.
Body composition and adiposity in LH-lesioned and pair-fed obese Zucker rats
Authors: Milam K. M. , Keesey R. E. , Stern J. S.
Published: December 2017

It has been reported previously that lateral hypothalamic (LH) lesions alter body composition including reducing adipocyte cellularity in lean and obese Zucker rats. The present experiment was designed to determine whether these alterations in body composition and adipose cell number are secondary to the reduced energy consumption of LH-lesioned rats or to a direct effect of the hypothalamic lesion. Groups of lean and obese Zucker rats, sustaining lesions of the lateral hypothalamus at 10 wk of age, maintained body weight at 72% that of nonlesioned controls until killed at 32 wk. Pair-feeding nonlesioned rats to the intakes of lean and obese LH-lesioned rats produced a reduction in adipocyte number similar to that caused by lesions. However, neither the lean nor obese LH-lesioned rats displayed an increase in cell number when fed a palatable diet that markedly increased carcass lipids. This finding suggests that adipocyte number may be constrained in LH-lesioned rats. These and further observations that 1) lean control rats maintained a higher body weight than the LH-lesioned rats to which they were pair fed and 2) in obese rats, food restriction further reduced protein deposition and elevated plasma insulin relative to comparably fed LH-lesioned obese rats suggest that the LH syndrome is mimicked by simple food restriction.
Clinical implications of glucocorticoid receptors in human leukemia
Authors: Lippman M.
Published: December 2017

Normal lymphoid cells contain glucocorticoid receptor. A variety of stimuli that activate these cells also induce increases in receptor concentration. Similar glucocorticoid receptors can be detected in lymphoid cells from patients with acute lymphoblastic leukemia (ALL). Absence of the glucocorticoid receptor (usually found in treated patients) predicts lack of glucocorticoid responsiveness. Furthermore, in our hands, glucocorticoid receptor levels correlate with the duration of complete remission in ALL (though not in other forms of leukemia). This association is independent of cell type, age, sex, or initial leukocyte count. The level of receptor shows a negative correlation with increasing aggressiveness of the tumor (null-cell leukemia greater than T-cell leukemia greater than Burkitt's lymphoma).
Estradiol stimulation of pituitary cAMP production and cAMP binding
Authors: Tang L. K. , Martellock A. C. , Tang F. Y.
Published: December 2017

The role of 17 beta-estradiol (E2) in the modulation of N6,O2'-dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP)-induced hormone release was examined in pituitary monolayer cultures prepared from intact and ovariectomized female rats. Incubations with 5 mM DBcAMP for 4 h significantly (P less than 0.05) stimulated both luteinizing hormone (LH) and prolactin (PRL) release in pituitary cultures prepared from rats at diestrus and from cycling rats at random stages of the estrous cycle. However, DBcAMP failed to stimulate the LH or PRL release in cultures prepared from ovariectomized rats in which the basal LH and PRL release was approximately three-fold and one-tenth of that in cycling rats, respectively. Pretreatment with 1 nM E2 augmented or restored the DBcAMP-induced LH release but not the DBcAMP-induced PRL release in cultures prepared from cycling or ovariectomized rats, respectively. Furthermore, E2 treatment alone of cultures prepared from cycling rats significantly increased intracellular cAMP concentrations and cAMP-binding activities by at least twofold over that of the non-E2-treated controls. The E2-induced rise in cellular cAMP concentration preceded the E2-induced rise in cAMP binding. These results indicate that the priming effect of E2 on pituitary LH responsiveness to DBcAMP is associated with increased cAMP production and cAMP binding.
Insulin binding and action in isolated rat hepatocytes: effect of obesity and fasting
Authors: Frank H. J. , Davidson M. B.
Published: December 2017

Insulin binding and action on [14C]glucose incorporation into glycogen were studied in freshly isolated hepatocytes from control, obese, and 48-h fasted-obese rats. Tracer 125I-insulin binding was reduced in the obese animals from 20.8 +/- 1.3% in the controls of 15.9 +/- 0.8% (mean +/- SE). The change in binding was due to a decrease in receptor number with no change in affinity. Fasting the obese animal for 48 h restored the tracer 125I-insulin binding and the receptor number to control levels. Physiologic concentrations of insulin caused an 86% stimulation of net [14C]glucose incorporation into glycogen above the basal level of 9.0 +/- 1.0 nmol incorporated . 10(6) cells-1 . h-1 with an ED50 of 4.0 ng/ml. In obese (greater than 500 g) animals the maximum insulin response measured by percent increase above basal (49%) was reduced, and the ED50 (5.8 ng/ml) was increased. When the obese animals were fasted, the basal and maximum insulin responses were further depressed, but the ED50 was restored to control levels. In conclusion, hepatocytes from obese animals show both a receptor and postreceptor defect. Fasting the animals restores the receptor status to normal, but the postreceptor metabolic defect remains.
Luteinizing hormone and testosterone secretion in young and old male mice
Authors: Coquelin A. , Desjardins C.
Published: December 2017

This study documents, for the first time, the temporal pattern of luteinizing hormone (LH) release and the relationship between plasma LH concentrations and testicular androgenic responses in young and aged male mice. Both LH and testosterone were measured in the same samples of blood plasma withdrawn at frequent intervals over 9 h from awake, mobile mice through intra-atrial cannulae. The results demonstrate unequivocally that LH and testosterone are discharged into the circulation in discontinuous pulses in this important animal model. Robust episodes of LH release occur at infrequent intervals and increments of circulating LH occasion time-delayed elevations of plasma testosterone. Thus, the frequency of LH release is the major factor determining peripheral concentrations of this gonadotropins. The obvious one-to-one coupling between intermittent LH discharges and testosterone secretion has significant functional and investigative implications. The reduction in circulating testosterone concentrations observed in old male mice is a consequence of fewer LH discharges, which is due most likely to the slowing of a neural GnRH pulse generator. However, age-related declines in copulatory behavior were not associated with altered patterns of hormone secretion. Hence, we suggest that deficits in sexual behavior and episodic LH release in old males result from neural senescence rather than diminished testicular support of reproduction.
Altered release of growth hormone and thyrotropin induced by endotoxin in the rat
Authors: Kasting N. W. , Martin J. B.
Published: December 2017

Plasma growth hormone (GH) and thyrotropin (TSH) levels were measured in freely behaving rats for 6 h on three consecutive days. On the 1st and 3rd days there was no treatment, and on the 2nd day endotoxin (150 mg/kg) was administered intravenously. Endotoxin causes a biphasic temperature response: an initial hypothermia persisting for 1 h, followed by hyperthermia evident from 5 to 8 h after injection. Normal pulsatile GH release observed on the 1st day was abolished on the 2nd day by the endotoxin treatment. On the 3rd day, however, GH secretion was greater than on the initial control day. TSH release was also suppressed by endotoxin and showed a rebound release on the subsequent day. The suppression of GH secretion by endotoxin was reversed in all animals by antisomatostatin serum, and the suppression of TSH secretion by endotoxin was reversed in some animals. These results suggest that endotoxin is a potent stimulus for hypothalamic somatostatin release in the rat. Endotoxin profoundly alters adenohypophyseal hormone release.
Stimulation of aldosterone biosynthesis by sodium sequestration: role of angiotensin II
Authors: Muller J. , Lund E. G. , Hofstetter L. , Brunner D. B. , Haldy P.
Published: December 2017

The role of angiotensin II in the stimulation of aldosterone biosynthesis by sodium sequestration in potassium-deficient rats was assessed by experiments involving 1-day angiotensin II infusion, converting enzyme inhibition, and bilateral nephrectomy. In intact rats, only an extremely high dose of exogenous angiotensin II imitated the stimulatory effects of polyethylene glycol-induced edema on the conversions of deoxycorticosterone and corticosterone to 18-hydroxycorticosterone and aldosterone. Treatment with the converting enzyme inhibitor captopril as well as bilateral nephrectomy blocked the aldosterone-stimulating action of edema. This inhibition was prevented by the simultaneous infusion of angiotensin II in captopril-treated rats but not in nephrectomized animals. According to these results, angiotensin II is an essential mediator in the stimulation of aldosterone biosynthesis by sodium sequestration. However, the role of the kidneys appears to be twofold. First, they act through the secretion of renin. In addition, a second yet unknown kidney factor is necessary for a full response of the zona glomerulosa to the stimulatory action of angiotensin II.
1,25-Dihydroxyvitamin C3-stimulated active uptake of phosphate by rat jejunum
Authors: Kabakoff B. , Kendrick N. C. , DeLuca H. F.
Published: December 2017

An assay system for measuring an active phosphate uptake in rat jejunal disks has been developed and used to study the rat's response to 1,25-dihydroxyvitamin D3. The active component of phosphate uptake is stimulated by added KCl, fructose, sodium, and CaCl2, but not MgCl2. Half-saturation values obtained with this assay are 0.08 mM (1,25-dihydroxyvitamin D3-treated) and 0.11 mM (D-deficient). The maximal velocities are 9.6 nmol . cm-2 . min-1 (D-deficient). Using a 5-min preincubation and a 15-min incubation, a dose-response curve for 1,25-dihydroxyvitamin D3 shows 6 pmol to be the lowest dose to give a significant response and 60 pmol to be the level at which the maximal response is reached. Measurement of phosphate uptake versus time after dosing with 1,25-dihydroxyvitamin D3 (300 pmol) revealed a biphasic response with peaks at 8 and 36 h and a trough at 20 h.
Tissue sites of catabolism of albumin in rabbits
Authors: Yedgar S. , Carew T. E. , Pittman R. C. , Beltz W. F. , Steinberg D.
Published: December 2017

The sites of albumin catabolism were determined in rabbits using [14C]sucrose-labeled rabbit albumin. The [14C]sucrose moiety is not degradable and accumulates in tissues degrading the protein. Albumin was labeled with [14C]sucrose, and the monomeric form was selected for injection into rabbits. The validity of the sucrose-labeled albumin as a tracer for native albumin was shown by the similar plasma decay kinetics of 125I-labeled albumin derivatized with sucrose and 131I-labeled native albumin and by the similar decay kinetics for the biologically screened and unscreened preparations of [14C]sucrose-albumin. Two days after injection of [14C]sucrose-albumin, tissues were assayed for accumulated 14C-labeled degradation products soluble in trichloroacetic acid. All tissues catabolized albumin with no tissue of predominant importance; liver, kidney, and muscle were the largest contributors. Expressed in terms of activity per unit wet weight, adrenal, kidney, spleen, ovary, bone marrow, and liver were the most active. These most active tissues are those with fenestrated or discontinuous capillary beds, suggesting that exposure to high concentrations of albumin is an important determinant of their high rates of albumin degradation.
Hyperphagia during lactation: satiety response to CCK and growth of the pancreas
Authors: McLaughlin C. L. , Baile C. A. , Peikin S. R.
Published: December 2017

Cholecystokinin (CCK) secreted from the duodenum during feeding has been shown to elicit satiety and stimulate growth of the pancreas in addition to affecting gastrointestinal function. In previous experiments hyperphagic Zucker obese rats were less sensitive to the effects of CCK on satiety and had a smaller pancreas than normal-weight rats. In the present experiments with hyperphagic lactating Zucker rats, the food intake response to exogenously administered CCK and the size and composition of the pancreas were measured. Food intakes after a 2-h fast were not decreased by 4.0 or 8.0 micrograms/kg CCK-8 during wk 1, 2, or 3 of lactation. However, in the same rats 2 wk after pups were weaned, 4.0 and 8.0 micrograms/kg CCK-8 decreased food intake 32% (2.1 +/- 0.4 vs. 3.1 +/- 0.3 g, paired t = 2.33, P less than 0.03) and 52% (1.5 +/- 0.2 vs. 3.1 +/- 0.5 g, paired t = 3.48, P less than 0.006). On day 18 of lactation, pancreas weight was increased 41% (1.38 +/- 0.05 vs. 0.98 +/- 0.02 g, paired t = 2.68, P less than 0.02) and contents of DNA, RNA, and protein were increased 57, 57, and 73%, respectively. Thus, hyperphagia in lactating female rats was associated with 1) decreased sensitivity to the satiety effect of CCK similar to that in hyperphagic obese rats and 2) hypertrophy of the pancreas in contrast to decreased pancreas size in obese rats.
Role of renal kallikrein in control of renin release in conscious rats
Authors: Kobayashi M. , Suzuki S. , Hashiba K.
Published: December 2017

Renal kallikrein was reported to activate human inactive renin and to release active renin from rat renal cortical slices. To evaluate the role of renal kallikrein in the control of renin release in vivo, Trasylol and soybean trypsin inhibitor (SBTI) were used to determine whether they can inhibit renin release stimulated by the administration of furosemide and a 2-wk low-sodium diet. Plasma renin activity (PRA) was increased by furosemide and also by the low-sodium diet. Urinary kallikrein excretion was increased by the sodium depletions. Trasylol did not affect basal PRA; however, it inhibited PRA and urinary kallikrein excretion, when stimulated by furosemide and by a low-sodium diet. These results suggest that furosemide and low-sodium diet act on the kidney to release renin via protease production. Because SBTI affected neither PRA nor urinary kallikrein excretion stimulated by these sodium depletions, it is suggested that renal kallikrein may play an important role in the control of renin release stimulated by furosemide and by low-sodium diet.
Amino acid metabolism in the ovine fetus
Authors: Lemons J. A. , Schreiner R. L.
Published: December 2017

Quantitative measurements of the umbilical uptake of a variety of substrates were made in the ovine fetus in both the fed state and after 5 days of maternal fasting. Blood flow was measured in both study periods using the antipyrine method, with the simultaneous measurement of umbilical vein and arterial concentrations of glucose, oxygen, and 25 amino acids in whole blood. Umbilical blood flow and fetal oxygen consumption remained unchanged between the fed and fasted states. Umbilical glucose uptake decreased from a mean of 6.85 to 2.79 mg X kg-1 X min-1 with a concomitant fall in the glucose:oxygen quotient from a mean of 0.70 to 0.31. Whereas the majority of gluconeogenic amino acids decreased in concentration in the maternal circulation during fasting, the branched-chain amino acids, as well as 3-methylhistidine, increased. In contrast the majority of amino acids in the fetal arterial circulation either increased significantly or remained unchanged in concentration. Although the fetal excretion of urea increased by 70% during the period of maternal fasting, the total fetal uptake of nitrogen in the form of free amino acids via the umbilical circulation did not change (1,337 vs. 1,027 mg X kg-1 X day-1). These data suggest that the supply of amino acids from the mother to the fetus does not change dramatically during maternal fasting. Therefore, the fetus must either catabolize amino acids previously destined for fetal tissue synthesis and/or begin catabolizing its own protein stores.
Defective sarcoplasmic reticular calcium transport in diabetic cardiomyopathy
Authors: Ganguly P. K. , Pierce G. N. , Dhalla K. S. , Dhalla N. S.
Published: December 2017

The effects of insulin and thyroid hormone treatments on cardiac sarcoplasmic reticular function were investigated in chronic streptozotocin-induced diabetes in rats. ATP-dependent Ca2+ transport and Ca2+-stimulated ATPase activities were depressed significantly in microsomal samples from diabetic rats in comparison with control (P less than 0.05). This defect was seen at various times of incubation (1-20 min) and different concentrations of free Ca2+ (10(-7) to 10(-5) M Ca2+) and was accompanied by changes in the protein composition and phospholipid contents of the microsomal fraction. The defect in calcium transport in microsomal vesicles was not evident until 28 days after streptozotocin (65 mg/kg iv) injection, whereas increases in plasma glucose levels due to insulin-deficiency occurred within 3 days. All changes in function and composition of the sarcoplasmic reticulum were reversed by insulin administration to the diabetic rats. Although the plasma level of thyroid hormone was decreased in the diabetic rat, thyroid hormone treatment did not restore microsomal calcium transport in the diabetic animals. The results of this study provide some evidence that the depression in cardiac sarcoplasmic reticular calcium accumulation during diabetes is a consequence of insulin deficiency and associated chronic metabolic changes but the hypothyroid condition that accompanies experimental diabetes does not appear to play any role in this defect.