bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in protein synthesis after trauma: importance of nutrition.
Authors: Stein T P , Leskiw M J , Wallace H W , Oram-Smith J C
Published: December 2017

The effect of trauma (femur fracture) on protein synthesis in rats given four different parenterally administered nutrient formulations ("diets") was investigated. Diet I was a maintenance formulation. It contained sufficient amino acids and glucose to keep the rats in nitrogen balance but was inadequate to support growth. Diet II was amino acids only, diet III was severely hypocaloric glucose, and diet IV was diet I minus the amino acids. The rats received parenterally all nutrients for the duration of the 4-5 day study. Twenty-four hours posttrauma, the fractional synthesis rates of liver, lung, heart, kidney, and muscle were estimated by infusing [15N]glycine for 17.5-19 h. (T.P. Stein, J.C. Oram-Smith, M.J. Leskiw, H.W. Wallace, L.C. Long, and J.M. Leonard. The effects of protein and calorie restriction on protein synthesis in the rat. Am. J. Physiol. 230: 1321-1326, 1976.) Two trends were found: i) on the amino acid-containing diets (I and II), most protein synthesis rates were increased posttrauma. Lung was the exception: no change was found; ii) rats on the amino acid deficient diets (III and IV) showed a decrease in the fractional muscle and lung synthesis rates posttrauma. We concluded that in this rat trauma model the requirement is mostly for amino acid nitrogen posttrauma.
Alterations in steroid binding plasma proteins in Macaca nemestrina during pregnancy.
Authors: Schiller H S , Holm R A , Sackett G P
Published: December 2017

We measured the corticosterone and dihydrotestosterone steroid binding capacities of corticosteroid-binding globulin (CBG) and sex steroid plasma binding protein (SBP) throughout pregnancy in seven Macaca nemestrina. The nSBP binding capacity rises significantly by 28 days of pregnancy, remains elevated through 56 days, tends to fall through midpregnancy, and then decreases dramatically to very low values 130-153 days after conception. In contrast, nCBG rises slightly (1.2-fold) in early pregnancy, is elevated in midpregnancy, but is similar to nonpregnant values during the last trimester of pregnancy. Our data indicate that factors controlling the plasma concentration of nCBG and nSBP are not identical. The results are in sharp contrast to those observed in human pregnancies in which both hSBP and hCBG are increased severalfold during pregnancy, including at term. Because the changes of nCBG and nSBP during pregnancy do not paralle the changes observed in human beings even though their steroid binding characteristics are similar, the M. nemestrina may serve as a valuable model for defining the physiologic function of SBP and CBG and the mechanism(s) controlling their concentrations in blood.
Postnatal development of circadian rhythms in disaccharidase activities in rat small intestine.
Authors: Saito M , Suda M , Matzuda H
Published: December 2017

The circadian rhythms in the activities of maltase and lactase of the small intestine were examined at various stages of postnatal development in rats. When the rats were fed ad libitum, no circadian change in the enzyme activities was found during the suckling period or the weaning period. However, several days after the time of weaning, the enzymes showed the same circadian changes as in adult rats with higher activities at night. After weaning, when the rats were fed only during the daytime, the phase of the enzyme rhythm shifted about half a day, and the highest activity was observed around feeding time. However, during the suckling period, no circadian rhythm in the enzyme acvities was found, even when the rats were allowed to feed only during a restricted time of the day.
Measurement of oxygen consumption and locomotor activity in monosodium glutamate-induced obesity.
Authors: Poon T K , Cameron D P
Published: December 2017

Oxygen consumption and locomotor activity were studied in mice developing obesity after neonatal administration of monosodium glutamate (MSG) and in untreated controls. MSG-treated mice became obese in the absence of increased food intake. Locomotor activity was significantly less in MSG-treated mice 2, 10, and 20 wk after weaning. Oxygen consumption expressed in terms of the Lee index was not significantly different at 2 wk after weaning although at 10 and 20 wk it was significantly lower in MSG-treated mice. Plasma thyroxine was not different between MSG-treated and control mice. It is suggested that diminished energy expenditure is the major factor in the etiology of obesity after neonatal administration of MSG.
Gastric HCO3--secretion in the guinea pig.
Authors: Garner A , Flemström G
Published: December 2017

Measurement of gastric intraluminal PCO2 and pH in the anesthetized guinea pig enabled simultaneous determination of total H+ and HCO3- gastric secretions. There was quantitative agreement between the release of CO2 and decrease in HCO3- after intragastric instillation of HCl. The basal rate of HCO3- secretion (approximately 40 mueq-h-1) was, in most cases, smaller than spontaneous H+ secretion, but gastric net secretory output was alkaline (HCO3- greater than H+) after inhibition of acid secretion with histamine H2-receptor antagonists (cimetidine 20 mg-kg-1 or metiamide 35 mg-kg-1). Carbachol (1-2 microgram-kg-1) stimulated secretion of both HCO3- and H+; only the latter response was sensitive to the histamine antagonists. Atropin (100 microgram-kg-1) blocked stimulation of HCO3- secretion but did not affect the basal output of HCO3-. An increase in HCO3- secretion was associated with an equivalent increase in net Na+ influx and an increase in the net influx of Cl- with H+ plus K+. Intragastric neutralization of H+ by HCO3- is likely to occur at the mucosal surface and may protect the mucosa from the damaging effects of intraluminal acid.
Adrenocortical metabolism of angiotensin in sheep with adrenal transplants.
Authors: Lun S , Espiner E A , Hart D S
Published: December 2017

Conscious trained sheep with adrenal gland autotransplants in cervical skin loops were used to study adrenocortical metabolism and clearance of angiotensin (AII) administered by constant systemic infusion. For comparative purposes similar experiments were undertaken in five control sheep with skin loops but no cervical adrenal tissue. During AII infusions (0.33 microgram/min for 30 min), loop venous-arterial AII ratios (0.42--0.62 were similar in both groups of sheep. Measured AII clearances across the skin loop in sheep with and without adrenal transplants were 400--600 and 100--150 pg/min, respectively, which correlated with blood flow (r = 0.79), but showed no relation to aldosterone secretion rate. Analysis of AII immunoreactive fragments showed similar proportions of octa-, hepta-, and hexapeptide fractions (64, 26, and 5%, respectively) in adrenal arterial, adrenal venous, and systemic venous plasma. These studies do not support selective heptapeptide uptake or metabolism by adrenal tissue in vivo and indicate that specific adrenal binding of AII is likely to be less than 400 pg/min at arterial AII concentrations approximating 120 pg/ml.
A miniature transducer for recording intestinal motility in unrestrained chronic rats.
Authors: Pascaud X B , Genton M J , Bass P
Published: December 2017

An extraluminal strain gage force transducer has been developed for recording gastrointestinal motility in small animals such as rats. Two commercial strain gages are bonded and wires attached to form half a Wheatstone bridge. The device is placed between silicone sheeting and prepared for implantation. As many as six implanted transducers can record simultaneously contractions and tone variations of circular or longitudinal gastrointestinal muscles. The transducers have been implanted in more than 20 rats, with some units lasting up to 4 mo. Furthermore, good relationships exist between intraluminal pressure waves registered by a small intraluminal balloon and gut contractions registered by the transducer. The transducers are a useful and accurate tool for rodent gut motility studies.
Pancreatic response to intestinal perfusion with lactic acid or acidified albumin.
Authors: Solomon T E , Grossman M I , Meyer J H
Published: December 2017

To test the hypothesis that the permeability of weak acids across the intestinal mucosa affects their ability to stimulate pancreatic bicarbonate output, we compared pancreatic bicarbonate secretion in response to intestinal perfusion with an acid presumed to be permeable to cell membranes, lactic acid (90 daltons), and an acid presumed to be impermeable, acidified bovine serum albumin (about 70,000 daltons). These two substances have similar titration curves from pH 2.00 to pH 4.50. In four conscious dogs with pancreatic fistulas, solutions of these weak acids were perfused at 50 ml/15 min into the intestine at concentrations adjusted to deliver 1, 2, or 4 mmol/15 min of acid titratable to pH 4.50 (threshold pH for bicarbonate stimulation) from an initial pH of 2.00 or 3.50. At both pH 2.00 and 3.50 and at all titratable acid loads, bicarbonate secretory responses to lactic acid and acidified albumin were not significantly different. Equal titratable acid loads of HCl produced much larger secretory responses. The data do not support the hypothesis that permeability of weak acids is a factor, but confirm the observation that weak acids are less potent than strong acids in stimulating pancreatic bicarbonate secretion.
Accumulation of radioiodine in thiouracil-hyperplastic thyroids of chicks.
Authors: Newcomer W S
Published: December 2017

Kinetics of accumulation of radioiodine was studied in thyroids of chickens before, during, and following ingestion of 0.25% thiouracil (TU). After a latent period of about 5 days, weight of the thyroid gland increased, reaching its maximum (42 mg/100 g body wt) after 21 days of TU ingestion; thyroid weight decreased immediately on withdrawal of TU but tended to plateau at a higher level than that of controls. One-way clearance increased by day 4 of ingestion of TU and reached its peak early during hyperplasia; it very quickly reverted to a control level on withdrawal of TU. Exit-rate constant increased markedly during early hyperplasia and decreased to a level less than normal after withdrawal of TU. Concentration of 127I decreased by a factor of 18 by 2 wk of feeding TU; it increased to practically a normal level by 1 wk after withdrawal of TU.
Diurnal changes in plasma glucose and insulin responses to oral glucose load in rats
Authors: Hara E. , Saito M.
Published: December 2017

The plasma glucose and insulin responses to an oral load of glucose were examined in the daytime and at night in unanesthetized and unrestrained rats. In rats that had been fed during the nighttime (2200-0400 h) every day for 2 wk, the plasma glucose and insulin responses were significantly greater (P less than 0.05) at night (2200-2400 h) than in the daytime (1000-1200 h). In rats that had been fed during the daytime (1000-1600 h), the plasma glucose and insulin responses were greater in the daytime than at night (P less than 0.05). It was concluded that the diurnal variations in the plasma glucose and insulin responses to an oral glucose load are closely related to the feeding schedule on which the rats are kept.
Leucogenenol a thymothyroid hormone
Authors: Rice F. A. , McCurdy J. D. , Oresajo C.
Published: December 2017

Thymectomy and, to a lesser extent, thyroidectomy cause a significant decrease in the serum leucogenenol levels of rats. Daily injections of neonatally thymectomized mice with leucogenenol causes the mice to maintain a normal level of neutrophils and lymphocytes in their circulation. The thymus and thyroid are the only tissues in rats and mice that afford radioactive leucogenenol when incubated in a medium containing radioactive D-glucose. It is concluded that the thymus and possibly the thyroid are responsible for the normal biosynthesis of leucogenenol in animals.
Calcium transport in small intestine during pregnancy and lactation
Authors: Halloran B. P. , DeLuca H. F.
Published: December 2017

The factors involved in calcium homeostasis during the mammalian reproductive cycle and specifically in the control of active calcium transport in the intestine have not been thoroughly investigated. For this reason calcium transport in the intestine was measured in vitamin D-replete and vitamin D-deficient rats during pregnancy and lactation using the everted gut sac technique. In addition the changes in the plasma concentrations of calcium and 1,25-dihydroxyvitamin D were measured and correlated with transport. During the later stages of pregnancy and during lactation, the concentration of calcium in the plasma is reduced 10-30%. In turn, in the vitamin D-replete rat, the concentration of 1,25-dihydroxyvitamin D in the plasma increases from a control value of 26 pg/ml to 158 pg/ml at day 14 of lactation. Calcium transport in the intestine increases late in pregnancy, peaks during lactation, and then falls to control values by 3 wk postweaning in both vitamin D-replete and D-deficient animals. These findings strengthen the established relationship between 1,25-dihydroxyvitamin D and active calcium transport in the intestine as well as suggest that some factor(s) independent of vitamin D is stimulating intestinal calcium transport during the reproductive cycle.
Hormonal modulation of adipose tissue lipoprotein lipase may alter food intake in rats
Authors: Steingrimsdottir L. , Brasel J. , Greenwood M. R.
Published: December 2017

Daily injections of 5 mg progesterone for 3 wk preferentially increased parametrial depot weight and fat cell size in ovarian intact rats. Adipose tissue lipoprotein lipase (LPL) activity was also preferentially increased in the parametrial depot. LPL activity increased at 24 h, whereas food intake did not increase until 36 h after the first injection. Parametrial fat cell size was significantly increased by 84 h and increased further by 3 wk. Daily injections of 2.5 microgram of estradiol for 3 wk decreased fat cell size and LPL activity in the parametrial depot of female rats, whereas in vitro glycerol release was unchanged. Serum triglycerides were increased, but free fatty acids were unaffected. The data suggest that ovarian hormones affected fat cell size in the rat through their modulation of LPL activity. These findings are consistent with the hypothesis that, during progesterone administration, preferential uptake of serum triglycerides into adipose stores decreases the availability of triglyceride-derived energy to the organism stimulating increased food intake.
Effect of NH4Cl on phosphaturic response to PTH in the hamster: dissociation from acidemia
Authors: Hoppe A. , Destro M. , Knox F. G.
Published: December 2017

Previous studies indicate that the hamster fasted for 16 h fails to demonstrate a significant phosphaturic response to parathyroid hormone (PTH). However, when hamsters were infused with ammonium chloride, a phosphaturic response to PTH was observed. The present studies evaluate the respective roles of acidemia and the ammonium ion in this response. As in previous studies, fasted thyroparathyroidectomized (TPTX) hamsters infused with PTH showed no significant increase in the fractional excretion of phosphate (FE rho), from 19 +/- 2 to 22 +/- 1%. Neither respiratory acidosis (hypercapnia) nor metabolic acidosis (HCl infusion) enhanced the phosphaturic effect of PTH, FE rho 21 +/- 4 to 20 +/- 6 and 15 +/- 2 to 16 +/- 3%, respectively. Both ammonium chloride and ammonium bicarbonate infusions enhanced the phosphaturic response; FE rho increased from 15 +/- 5 to 27 +/- 5% (P < 0.02) and 17 +/- 3 to 25 +/- 3% (P < 0.05), respectively. We conclude that the enhancement of the phosphaturic effect of PTH in the fasted hamster by ammonium chloride infusions can be dissociated from acidemia.
Utilization of leucine by working rat heart
Authors: Ichihara K. , Neely J. R. , Siehl D. L. , Morgan H. E.
Published: December 2017

Leucine provided substrate to partially support mechanical activity of working rat hearts; the beneficial effect on peak systolic pressure development was more marked as leucine concentration was increased to 10 mM. In Langendorff preparations that had been exposed to 5 mM [U-14C]leucine, the imposition of cardiac work was accompanied by a threefold increase in the rate of 14CO2 production within the first 30 s; however, the rate decreased 40% in the next 10 min. This transient acceleration of 14CO2 production was not observed when [1–14C]leucine was provided and appeared to be due to oxidation of a tissue pool of radioactive intermediates that was present after 10 min of Langendorff perfusion. Over a period of 1 h, oxidation of either [U-14C]- or [1–14C]leucine increased 25–40% in working compared to Langendorff preparations that were supplied 5 mM leucine and 11 mM glucose. In working hearts that were supplied a substrate and hormone mixture that simulated normal plasma and 1 mM leucine, a concentration found in the plasma of diabetic but not normal rats, leucine oxidation was accelerated 73% by work but amounted to only 3.3% of oxygen consumption.
Lack of effect of morphine, reserpine, and halothane on oscillation of plasma insulin in M. mulatta
Authors: Hom F. G. , Koerker D. J. , Goodner C. J.
Published: December 2017

Oscillating plasma insulin levels, with periods averaging 9 min, in fasting rhesus monkeys have been previously reported by us. To test whether an oscillator in the central nervous system might be driving these oscillations, we subjected five male rhesus monkeys to morphine, reserpine, and halothane, agents known to affect the central nervous system, in an attempt to either disrupt or change the frequency of the oscillations. We could demonstrate no significant effect of any of the three drugs on the oscillations. We conclude, therefore, that the oscillations in plasma insulin are not driven by an oscillator in the central nervous system. Coupled with the results of others, these data suggest that these oscillations are probably due to an intrinsic pancreatic pacemaker.
Cold-induced developmental changes in fat cell size and number in brown adipose tissue of the rat
Authors: Senault C. , Cherqui G. , Cadot M. , Portet R.
Published: December 2017

Seven-week-old Long-Evans rats were acclimated to a constant temperature of either 28 degrees C (control group) or 5 degrees C (cold-acclimated group). Cold acclimation induced a 70% increase in the interscapular brown adipose tissue (IBAT) relative mass, a 35% increase in DNA content, and a 44% decrease in triglyceride (TG) content, which resulted in a 51% decrease of the TG/DNA ratio. A procedure is described by which brown fat cells were isolated, with a yield of 21% from the IBAT of the control group and of 38% in the cold-acclimated group. In both groups, the brown fat cells accounted for 35-37% of the total cells in the tissue. Cold acclimation induced decreases in the mean fat cell diameter (about 20%), the mean fat cell TG content (50%), and the fat cell TG/DNA ratio (50%). The total number of IBAT fat cells was significantly increased in cold-acclimated rats. It is concluded that cold acclimation involves a hyperplasia of the IBAT, associated with a decrease of fat cell size without any alteration of the fat cell-to-nonfat cell ratio.
Angiotensin II stimulates guanylate cyclase activity in aorta, heart, and kidney
Authors: Vesely D. L.
Published: December 2017

The objective of the present investigation was to determine whether angiotensin II at physiological levels has part of its mechanism of action through stimulation of the activity of guanylate cyclase (EC 4.6.1.2), the enzyme that catalyzes the conversion of guanosine triphosphate to cyclic GMP. Angiotensin II enhanced guanylate cyclase activity three-to fivefold in rat aorta, heart, and kidney at a concentration of 1 nM. Dose-response curves revealed that near maximal stimulation of guanylate cyclase with angiotensin II was observed at a concentration as low as 10 pM. The guanylate cyclase cofactor manganese was necessary for the maximal enhancement of guanylate cyclase by angiotensin II. The data in this investigation suggest that guanylate cyclase may play a role in the mechanism of action of angiotensin II at the cellular level.
Endogenous hyperglycemia restores insulin release impaired by somatostatin analogue
Authors: Taborsky G. J. , Porte D.
Published: December 2017

These studies assessed the ability of des-Asn5-[D-Trp8-D-Ser13]-somatostatin (d-ATS-SS) to selectively inhibit insulin release and produce a hyperglycemia sufficient to compensate for the original impairment. d-ATS-SS at 0.017 micrograms/min inhibited basal insulin output (delta = -38 +/- 6%, P less than 0.005) and increased basal pancreatic glucagon output (delta - +21 +/- 6%, P less than 0.05, n = 5). d-ATS-SS at 0.17 micrograms/min markedly inhibited insulin output (delta = -84 +/- 4%, P less than 0.0005) and slightly inhibited glucagon output (delta = -14 +/- 6%, P less than 0.05, n = 5). d-ATS-SS at 0.055 micrograms/min decreased basal and stimulated insulin release but not basal nor stimulated glucagon release. By 3.5 of analogue infusion, plasma glucose had risen by 116 +/- 13 mg/dl, and base-line insulin levels and the insulin responses to both isoproterenol and arginine, but not glucose, increased toward control values. We conclude that d-ATS-SS produces selective insulinopenia resulting in hyperglycemia which in turn compensates for the original impairment. Thus, the hyperglycemia observed in other states of selective insulin deficiency (e.g., noninsulin-dependent diabetes mellitus) may compensate for defects in beta-cell function.
Ventral and dorsal areas of rat pancreas: islet hormone content and secretion
Authors: Trimble E. R. , Renold A. E.
Published: December 2017

Islets isolated from the dorsal and ventral areas of the rat pancreas (dorsal and ventral islets) were found to have similar insulin and total protein contents. Dorsal islets, however, contained more glucagon and somatostatin than ventral islets. Dorsal islets secreted significantly more insulin in the presence of 16.7 mM glucose and 20 mM D-glyceraldehyde than did ventral islets. Leucine-induced (20 mM) insulin secretion from the two types of islet was similar. The amounts of somatostatin secreted by the two types of islet were similar both in the presence of 16.7 mM glucose and in the presence of 20 mM D-glyceraldehyde. By contrast, more glucagon was secreted by dorsal than by ventral islets in the presence of 16.7 mM glucose. It was found that the difference in glucagon secretion between the dorsal and ventral islets in the presence of 16.7 mM glucose may be an explanation for the difference in the rate of insulin secretion under these conditions. The results suggest that glucagon may exert an important intraislet control on insulin secretion.
Effect of counterregulatory hormones on kinetic response to ingested glucose in dogs
Authors: Sacca L. , Cicala M. , Corso G. , Ungaro B. , Sherwin R. S.
Published: December 2017

The disposal of ingested glucose was quantitated in dogs during individual and combined infusion of glucagon, epinephrine, and cortisol. Initial splanchnic extraction of ingested glucose, endogenous glucose production, and glucose uptake were quantitated using a double-tracer technique. Glucagon or cortisol individually had no effect on the kinetic response to glucose ingestion, whereas epinephrine increased glucose levels by 50–100 mg/dl. Epinephrine caused a reduced suppression of glucose production and a marked inhibition of the initial rise in glucose uptake. Initial splanchnic glucose extraction, plasma insulin, and glucagon were not significantly altered. The addition of glucagon and cortisol to epinephrine did not accentuate hyperglycemia, except after 150 min when glucose production increased. We conclude that a) epinephrine produces glucose intolerance when infused individually, b) this effect is primarily dependent on inhibition of glucose uptake and, to a lesser extent, on a reduction in suppression of endogenous glucose output, and c) addition of glucagon and cortisol has only a minor effect on epinephrine-induced changes in glucose disposal. Our data suggest an important role of epinephrine in stress-induced glucose intolerance.
Enhanced skeletal muscle insulin sensitivity in year-old rats adapted to hypergravity
Authors: Mondon C. E. , Dolkas C. B. , Oyama J.
Published: December 2017

Rats adapted to hypergravity by continuous centrifugation at 4.15 g for 7 mo exhibit increased glucose uptake at lower plasma insulin levels than weight-matched control animals following oral glucose administration. To assess insulin sensitivity of specific tissues, glucose uptake by perfused skeletal muscle and liver from year-old hypergravic rats was compared with perfused tissue from weight-matched control rats (2.5-mo-old). The results show that metabolic clearance of glucose by skeletal muscle from hypergravic rats ws not significantly greater than control muscle when perfused in the absence of insulin (10.6 vs. 8.1 microliter.min-1.g muscle-1) but was twofold faster (23.0 vs. 9.5) at perfusate insulin levels of 35 microunits/ml. Conversely, glucose uptake by hypergravic livers was significantly decreased (P less than 0.001) compared with control livers (10.3 vs. 27.8) at perfusate insulin levels of 40 microunits/ml. These findings suggest that skeletal muscle rather than liver is the tissue primarily responsible for enhanced sensitivity to insulin observed in older rats adapted to hypergravity.
Role of epinephrine for muscular glycogenolysis and pancreatic hormonal secretion in running rats
Authors: Richter E. A. , Sonne B. , Christensen N. J. , Galbo H.
Published: December 2017

We have previously shown that during swimming muscular glycogen breakdown was diminished and plasma glucagon and insulin were lower and higher, respectively, in adrenodemedullated rats compared to controls. These findings might be due to a lower work intensity or higher efficiency in adrenodemedullated rats than in controls. Furthermore, they might be due to either an acute or a chronic influence of epinephrine. Rats were adrenodemedullated (DM) or sham-operated (C). They were chronically cannulated and either rested or ran in a metabolism chamber for 45 min. Running DM rats had either saline (DM-S) or epinephrine (normalizing the concentration in plasma) (DM-E) infused. During running, oxygen uptake was identical in C and DM rats. Muscular glycogen breakdown was similar in DM-E and C rats and higher than in DM-S rats. Blood glucose, lactate, and heart rate increased in C and DM-E, but not in DM-S rats. In spite of the differences in blood glucose, plasma insulin was the same in all groups and plasma glucagon increased identically in all running rats. Plasma FFA and liver glycogen were similar in all groups. In conclusion. in running rats, epinephrine exerts an acute enhancing effect on muscular glycogenolysis, glucagon secretion, and heart rate and an acute depressing effect on insulin secretion.
Estradiol-induced changes in lipoprotein lipase, eating, and body weight in rats
Authors: Ramirez I.
Published: December 2017

Daily injections of 5 micrograms estradiol benzoate (EB) for 1, 2, 3, and 12 days decreased parametrial and retroperitoneal adipose tissue lipoprotein lipase activity in ovariectomized rats. Nearly all of this decrease occurred within the 1st day. In contrast, EB-induced body weight loss and hypophagia were very slight during the 1st day after EB administration and increased substantially over the next 2 days. EB did not affect gastrocnemius muscle lipoprotein lipase activity over the first 3 days, but did decrease muscle lipoprotein lipase activity after 12 days. These changes in adipose and muscle lipoprotein lipase activity suggested that EB-induced redistribution of fuel would be greater after 3 days of treatment than after 12 days of treatment. Tests with two different in vivo triglyceride uptake methods confirmed this suggestion. EB-treated rats were hypertriglyceridemic after 12 days of treatment, but not after 3 days of treatment. Elevated plasma triglycerides were associated with an increased rate of triglyceride entry. These findings are consistent with the hypothesis that EB administration temporarily results in redistribution of triglyceride fuel from adipose tissue to muscle, resulting in a transient decrease in rate of weight gain.
Alteration of hepatic glycogen synthase phosphatase activity by insulin deficiency
Authors: Miller T. B. , Vicalvi J. J. , Garnache A. K.
Published: December 2017

Perfused livers from normal and alloxan-diabetic rats were studied to determine whether the diabetes-related decrease in glycogen synthase phosphatase was due to an alteration of the synthase molecule, an increase in synthase phosphatase activity inhibition by phosphorylase a, or generation of inhibitor of the phosphatase. With purified rat liver synthase as substrate for the phosphatase, the diabetic tissue remained 90–95% deficient in the ability to catalyze synthase D to I conversion, showing that the defect cannot be solely due to an altered substrate. When synthase phosphatase assays were carried out in the presence of rat liver glycogen phosphorylase antiserum, phosphatase activity remained 70–75% deficient in diabetic tissue. Therefore, the defect cannot be attributed to increased inhibition of synthase phosphatase by increased amounts of phosphorylase a. When synthase phosphatase assays were run by mixing extracts from normal and diabetic livers, phosphatase activity was additive, indicating that a phosphatase inhibitor was probably not involved in the phosphatase deficiency in the diabetic. These data are consistent with the hypothesis that the diabetes-related defect in glucose regulation of hepatic glycogen synthase is due to a molecular alteration or a deficiency of a specific glycogen synthase phosphatase.
Whole-body leucine and lysine metabolism: response to dietary protein intake in young men
Authors: Motil K. J. , Matthews D. E. , Bier D. M. , Burke J. F. , Munro H. N. , Young V. R.
Published: December 2017

Whole-body leucine and lysine metabolism was explored in young adult men by a primed constant intravenous infusion of a mixture of L-[1–13C]leucine and L-[alpha-15N]lysine over a 4-h period. Subjects were studied after an overnight fast (postabsorptive state) or while consuming hourly meals (fed state) after adaptation to diets providing either a surfeit level of protein (1.5 g.kg body-1.day-1), a level approximating maintenance requirements (marginal intake) (0.6 g.kg body wt-1.day-1), or a grossly inadequate level (0.1 g.kg-1.day-1). The change in protein intake from a marginal to a surfeit level was associated with an increased leucine flux and incorporation of leucine into body protein. In the fed state, oxidation of leucine increased sharply and release of leucine from tissue protein diminished. When dietary protein intake was reduced from the requirement to inadequate level, leucine flux and body protein synthesis and protein breakdown were reduced, together with a smaller reduction in leucine oxidation. The response of the metabolism of [15N]lysine was responsible for maintenance of leucine and other essential amino acid economy, and they appear to be related to the nitrogen and amino acid requirements of the subject. These findings also demonstrate an effect of meals, modulated by their protein content, on the dynamics of whole-body amino acid metabolism.
Episodic secretion of parathyroid hormone in the dog
Authors: Fox J. , Offord K. P. , Heath H.
Published: December 2017

This study was designed to determine whether parathyroid hormone (PTH) is secreted episodically, to characterize any such rhythms, and to see whether the rhythms can be altered by stimulating PTH secretion using constant hypocalcemia. We collected blood samples at 1-min intervals for 1 h from the precava or postcava of conscious dogs during normocalcemia or induced, constant hypocalcemia. In two anesthetized normocalcemic dogs we catheterized a caudal thyroid vein and collected all the effluent blood in 1-min fractions. Immunoreactive PTH (IPTH) concentrations were determined in quadruplicate, and the results were subjected to spectral analysis. In both the precava and postcava of normocalcemic dogs, there were regular oscillations in IPTH levels with a period of 12 min (range, 10–15 min) and a +/- 14% variation about the overall mean. Although significant two- to fourfold changes in IPTH levels still occurred during constant hypocalcemia, there was no significant rhythmicity. Significant cycles in IPTH concentration (mean 8.4-min period) were observed in thyroid venous effluent plasma during normocalcemia, confirming that the phenomenon represented episodic secretion that was not affected by pentobarbital anesthesia.
Evidence that brain aromatization regulates LH secretion in the male dog
Authors: Worgul T. J. , Santen R. J. , Samojlik E. , Irwin G. , Falvo R. E.
Published: December 2017

A variety of data suggest an independent role for androgens and estrogens in the regulation of luteinizing hormone (LH) secretion in the male. Estrogens, in the male are primarily derived from testicular androgens that are aromatized both in peripheral tissues and in the CNS. Our prior data suggested a pharmacologic regimen that blocked CNS aromatization without lowering peripheral estrogen or testosterone levels. Such experimental conditions would permit assessment of the relative roles of CNS versus peripheral aromatization in the regulation of LH secretion. We utilized this regimen (aminoglutethimide, a potent aromatase inhibitor, and hydrocortisone) in seven adult male dogs for 14 days. Plasma LH rose to castrate levels, 450% above control values on days 7 and 14. These LH increments stimulated similar rises in androstenedione, testosterone, and dihydrotestosterone. In contrast, plasma estrone and estradiol concentrations remained constant. The induction of castrate LH levels without a concomitant fall in peripheral androgens or estrogens is best explained by a block of central aromatization and thus a reduction in local hypothalamic concentrations. We conclude that aromatization in the CNS rather than peripheral tissues is the more important site with respect to LH negative feedback in the male dog.
Body composition, energy expenditure, and plasma metabolites in long-term fasting geese
Authors: Le Maho Y. , Vu Van Kha H. , Koubi H. , Dewasmes G. , Girard J. , Ferre P. , Cagnard M.
Published: December 2017

Starvation in 15 geese (mean initial body mass, m = 6.3 kg) fasting for about 40 days (mean decrease in m = 2.5 kg) was characterized by three periods. Period I (3-8 days), an adaptation period, was marked by a considerable decrease in the daily rate of change in m (dm) as well as in resting metabolic rate (RMR), and by high fat mobilization. In period II (a period of economy) the decreases in dm, RMR, and daily rate of nitrogen excretion (dne) were reduced: when expressed per unit of body mass these rates were either constant or decreased slightly. Period III, a critical period, was characterized by a rapid increase in both dm and dne that appeared when body mass had dropped to 4.7-3.2 kg. In parallel there was a greater decrease in intracellular fluid volume below 5 kg. Throughout the fast, in contrast to fasting mammals, plasma glucose and alanine concentrations were maintained at high levels (8-10 and 0.4 mM, respectively), and there was no increase in acetoacetate. However, after 20 days of fasting, plasma beta-hydroxybutyrate concentration (beta-OHB) increased to about 20 mM, while blood pH remained constant and blood PCO2 decreased. Thus, compensation for metabolic acidosis was partly attributed to respiratory alkalosis. Throughout the fast, the variations in beta-OHB were a mirror image of those for daily changes in body mass and in nitrogen excretion. This presumably reflects a hormonal change, but might also suggest a key role of beta-OHB in the control of energy expenditure and/or in regulation of body mass as well as in protein sparing.
Induction of luteolysis by dihydrotestosterone in the pregnant rat
Authors: Sridaran R. , Gibori G.
Published: December 2017

A dihydrotestosterone (DHT) pellet (4 mg) inserted under each ovarian bursa on day 9 of pregnancy induced within 24 h, a 40% decline in serum progesterone (P) concentrations in rats; a further reduction was observed on days 12 and 15. Although P levels were significantly reduced by DHT treatment, fetuses remained alive on day 12. However, by day 15, complete abortion occurred in 75% of the rats, indicating that a decline in P secretion precedes abortion, To further determine whether the abortifacient action of DHT was due to its luteolytic effect, 20-cm DHT capsules were implanted subcutaneously in ovariectomized rats treated with 4 mg P and 0.5 micrograms of estradiol (E). Control rats were sham-operated and treated with empty capsules. DHT treatment induced complete abortion by day 15 only in rats with ovaries present, further indicating that DHT was not directly detrimental to the fetuses but acted on the ovaries to induce luteolysis. When DHT treatment was started on day 12, no luteolytic effect was detectable. To determine whether the effect of DHT was mediated by either a decrease in the ovarian production of E, a decline in luteal cell content of luteinizing hormone (LH) receptors or both, testosterone (T) levels in the peripheral circulation and E and P concentrations in the ovarian vein were measured on day 15 in rats implanted with two DHT pellets under the ovarian bursa on day 9. Luteal content of LH receptors was also measured on day 12 in similarly treated rats. DHT treatment had no effect on serum levels or on ovarian vein concentration of E, but induced a significant decrease in the ovarian vein levels of P. DHT also did not depress LH receptor content in corpora lutea. DHT levels in the ovaries increase significantly between days 18 and 22 of pregnancy, concomitant with the cessation of corpus luteum function. These results indicate that DHT possesses a potent luteolytic activity and could be involved in the luteolytic process in the pregnant rat.
Effect of insulin on fat and protein deposition in diabetic lean and obese rats
Authors: Chan C. P. , Koong L. J. , Stern J. S.
Published: December 2017

Five-week-old male obese and lean Zucker rats were made comparably diabetic by intracardiac injections of alloxan (65-72 mg/kg body wt). Lean rats were then given daily injections of protamine zinc insulin at 3 doses: 0.25, 1.25, and 4.0 U.100 g body wt-1.day-1 for 3 wk. Obese rats received identical amounts as corresponding lean controls independent of body weights. The drop of blood glucose concentration after injections of regular insulin and the percentage fall in radioactive plasma insulin after injections of 125I-insulin were comparable in lean and obese rats. Weight gain, fat gain, and protein gain over 21 days increased with increasing amounts of insulin administered. However, at the same dose of insulin, although weight gain was comparable, fat gain was higher and protein gain was lower in obese rats when compared to lean controls. These results suggest that the enhanced lipid deposition of the obese Zucker rat is not totally dependent on insulin levels, but is exaggerated by hyperinsulinemia.
Mechanism of hyperinsulinemia after reticuloendothelial system phagocytosis
Authors: Filkins J. P. , Yelich M. R.
Published: December 2017

Endocytic loading of the reticuloendothelial system (RES) results in acute hyperinsulinemia and functional hyperinsulinism. Colloidal carbon blockade of the RES in rats resulted in elevations of both portal vein and systemic serum immunoreactive insulin and increases in the hepatic portal vein insulin glucose ratios. Two mechanisms for the hyperinsulinemia were evaluated: 1) decreased removal of insulin by the postendocytic liver and 2) increased secretion of insulin by the isolated perfused pancreas. Colloidal carbon blockade did not alter removal of 125I-insulin as evaluated in the isolated perfused rat liver. Pancreases from postendocytic donor rats when perfused according to the technique of Grodsky manifested enhanced insulin secretion. Macrophage culture-conditioned media enhanced glucose-mediated insulin secretion both as assayed in vivo and in the isolated perfused rat pancreas. The data suggest that postendocytic activated macrophages secrete a monokine that alters insulin release and thus produces the hyperinsulinemia of RES blockade. The acronym MIRA for macrophage insulin-releasing activity is proposed for the monokine.
Influence of parathyroid state on calcium uptake in bone
Authors: Lemon G. J. , Bassingthwaighte J. B. , Kelly P. J.
Published: December 2017

The exchange of calcium and strontium ions in bone was studied in control dogs, dogs made hypocalcemic by parathyroidectomy, and dogs rendered hypercalcemic by injection of parathyroid hormone. After injections of tracer into the tibial nutrient artery, extraction of tracer during transcapillary passage was measured and expressed as a fraction of 1. Extraction over the first 3 min in normal dogs was 0.46 +/- 0.09 (n = 6), in hypocalcemic dogs it was increased to 0.53 +/- 0.07 (n = 6), and in hypercalcemic dogs it was decreased to 0.39 +/- 0.07 (n = 5). Subsequent washout was less rapid than normal in hypoparathyroid dogs and more rapid than normal in hyperparathyroid dogs. We conclude from this that the immediate volume of distribution in bone (or the number of available binding sites) for strontium diminishes as the parathyroid hormone level increases.
Developmental aspects of pituitary and adrenal responses to arterial hypotension in neonatal, weanling, and adult sheep
Authors: Rose J. C. , Morris M. , Meis P. J.
Published: December 2017

We have studied neuroendocrine and heart rate responses to arterial hypotension in unanesthetized, chronically cannulated neonatal (less than 10 days old), weanling (3- to 4-wk-old), and adult sheep. Nitroprusside-induced arterial hypotension in the absence of hypovolemia promptly increased plasma ACTH, vasopressin (AVP), and cortisol levels in all three groups. The integrated adenohypophyseal and neurohypophyseal responses to a standard hypotensive stimulus were similar at the three ages, suggesting that the functional development of the systems subserving these responses is complete by the immediate postnatal period. The integrated cortisol/ACTH ratio was greatest in the youngest animals, suggesting that enhanced adrenal responsiveness to ACTH exists in neonatal as well as in late-gestation fetal lambs. The reflex tachycardia accompanying the arterial hypotension in the weanling and adult sheep was absent in the neonates.
Effect of vasoactive intestinal polypeptide on glycogen metabolism in rat hepatocytes
Authors: Wood C. L. , Blum J. J.
Published: December 2017

The effects of vasoactive intestinal polypeptide (VIP) on several enzymes of glycogen metabolism in rat hepatocytes were compared with those of glucagon and of vasopressin (ADH). VIP caused phosphorylase activation and glycogenolysis in hepatocytes from fed rats. In hepatocytes from fasted rats incubated with glucose, lactate, and pyruvate, VIP inhibited net glycogen deposition, inactivated glycogen synthase, and activated phosphorylase. VIP was about 100-fold less potent than glucagon and 1,000-fold less potent than ADH in causing activation of phosphorylase. The ability of VIP to activate phosphorylase was not altered by chelation of the calcium in the medium. The half maximal effective doses of VIP for both phosphorylase activation and stimulation of glycogenolysis were 10-30 nM. Treatment with VIP, ADH, or glucagon did not decrease phosphorylase phosphatase activity. Each of these hormones, however, lengthened the lag time before synthase phosphatase activity was expressed in vitro. Other gut hormones tested did not affect hepatocyte glycogen metabolism. These results do not support the concept of physiologic control of hepatic glycogen metabolism by VIP or by other gut hormones.
Morphine suppresses plasma catecholamine responses to laparotomy but not to 2-deoxyglucose
Authors: Taborsky G. J. , Halter J. B. , Porte D.
Published: December 2017

The increase of plasma catecholamines that occurs during surgery can be reduced by administration of morphine. To test the hypothesis that morphine specifically blocks nociceptive stimulation during surgery, we compared the effects of morphine administration on the plasma catecholamine response to a laparotomy in pentobarbital-anesthetized dogs with the effect of morphine on the plasma catecholamine response to the neuroglucopenic agent, 2-deoxy-D-glucose (2DG, 300 mg/kg iv). In control dogs, plasma epinephrine (Epi) and plasma norepinephrine (NE) both increased progressively with time following a midline laparotomy (delta Epi by 50 min, +133 +/- 42 pg/ml, P less than 0.01 and delta NE by 50 min, +108 +/- 38 pg/ml, P less than 0.01, mean +/- SE, n = 12). 2-Deoxy-D-glucose produced a similar increase of both plasma NE and Epi. In dogs that received the anesthesia alone, plasma catecholamines did not increase from base line during the experiment. The analgesic morphine (15 mg iv), given 15 min after the completion of laparotomy, not only prevented the progressive rise of plasma catecholamines after laparotomy, but also caused a small but significant decline (P less than 0.05). Naloxone (0.4 mg iv) totally reversed the suppressive effects of morphine, restoring both catecholamines to the levels of their time-related control. In marked contrast, neither morphine nor naloxone affected the plasma NE and Epi increases following the administration of 2DG. These data suggest that morphine suppression of plasma catecholamines during surgery is not due to a generalized attenuation of sympathetic outflow, but rather to a specific interaction with an opiate receptor that either mediates analgesia or lies within the neural pathway stimulated by laparotomy but not by 2DG.
Calcium homeostasis in chronic streptozotocin-induced diabetes mellitus in the rat
Authors: Hough S. , Russell J. E. , Teitelbaum S. L. , Avioli L. V.
Published: December 2017

Calcium homeostasis was studied in freely fed control, streptozotocin diabetic, long-term and short-term insulin-treated diabetic rats 7 wk after the induction of diabetes. In contrast to the short-term (5-12 day) diabetic rat model, intestinal absorption of calcium was markedly enhanced in chronically insulin-deficient animals. Moreover, conventional balance studies showed that these animals were in positive calcium balance despite severe hypercalciuria. Intestinal hyperabsorption of calcium in long-standing diabetic rats occurred despite low levels of circulating 1,25-dihydroxyvitamin D and hypercorticosteronism and was attended by hypercalcemia and suppression of both plasma parathyroid hormone (PTH) and urinary cyclic 3',5'-AMP (cAMP). Long-term insulin replacement completely normalized the intestinal hyperabsorption of calcium, corrected the plasma calcium, and significantly increased circulating PTH and urinary cAMP excretion. Insulin therapy also corrected the decreased plasma 1,25-dihydroxyvitamin D observed in untreated diabetic animals. Intestinal hyperabsorption of calcium appeared to be only partially corrected by short-term insulin therapy. The accumulated results reveal decided differences in calcium homeostasis and hormonal response between the rats with long-standing diabetes and those with diabetes of short duration.