bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-body leucine and muscle protein kinetics in rats fed varying protein intakes
Authors: Laurent B. C. , Moldawer L. L. , Young V. R. , Bistrian B. R. , Blackburn G. L.
Published: December 2017

Whole-body leucine kinetics and rectus muscle synthetic rates were evaluated in postabsorptive rats fed semipurified diets that varied in the casein content. Rats were allowed to consume ad libitum a 2% casein diet or were pair-fed or ad libitum-fed 6, 20, or 40% casein diets for 14 days. After overnight starvation, rates of whole-body leucine kinetics and rectus muscle synthetic rates were determined with a 2-h constant intravenous infusion of L-[1-14C]leucine. The postabsorptive response to inadequate protein intakes included a significant reduction in the release of leucine from whole-body protein degradation as well as subsequent reutilization for protein synthesis. In contrast, dietary protein intake at levels greater than required for maximal growth were not associated with any increases in leucine incorporation into whole-body protein or muscle fractional synthetic rates. Rates of whole-body leucine oxidation based on plasma leucine specific radioactivities underestimated total oxidation by 22-27%, and this was relatively constant as the protein component of the diet was varied. In addition, the muscle acid-soluble leucine specific radioactivity was similar to the plasma alpha-ketoisocaproate enrichment, regardless of dietary protein intake.
Effects of ammonium chloride on resorption of fetal rat bones in organ culture
Authors: Johannesson A. J. , Raisz L. G.
Published: December 2017

Ammonium chloride, a known inhibitor of lysosomal function, was found to be a rapid and potent inhibitor of 45Ca release from fetal rat bones in organ culture. The response to parathyroid hormone and prostaglandin E2 was inhibited in a dose-related, reversible fashion. The activity of the lysosomal enzyme beta-glucuronidase in the medium closely paralleled 45Ca release. Ammonium chloride may now be added to the list of antilysosomal agents that inhibit bone resorption in vitro.
Catecholamine responses and their interactions with other glucoregulatory hormones
Authors: Vranic M. , Gauthier C. , Bilinski D. , Wasserman D. , El Tayeb K. , Hetenyi G. , Lickley H. L.
Published: December 2017

We have investigated catecholamine-glucagon-insulin interactions using three stress models: 1) hypoglycemia; 2) exercise; and 3) epinephrine infusion. Phlorizin caused mild hypoglycemia with hypoinsulinemia. Plasma glucagon increased as did hepatic glucose production. Catecholamines did not increase. Insulin caused severe hypoglycemia. Metabolic counterregulation was due mainly to the 40-fold increase in epinephrine. Glucagon played a role only in the recovery from insulin-induced hypoglycemia, which could reflect increased hepatic sensitivity to glucagon with declining plasma insulin. Glucagon suppression during exercise caused transient hypoglycemia due to an inadequate rise in glucose production. Exaggerated epinephrine release during hypoglycemic exercise prevented severe hypoglycemia by inhibiting glucose utilization and stimulating glucose production, with an associated increase in lactate and free fatty acid levels. Hypoglycemic exercise also caused increased cortisol release. Counterregulation was prevented by a euglycemic clamp. We conclude that, during exercise, glucagon is directly responsible for 80% of the increment of glucose production and controls glucose uptake by the muscle indirectly; thus glucagon spares muscle glycogen by increasing hepatic glucose production. Epinephrine infusion in normal dogs caused a transient increase in glucose production and a sustained inhibition of glucose clearance, resulting in hyperglycemia. Insulin rose transiently, followed by a relative inhibition of secretion. Glucagon suppression did not modify the metabolic effects of epinephrine. In alloxan-diabetic dogs, the glucagon response to epinephrine was augmented, whereas in depancreatized dogs, during subbasal insulin infusion, the hepatic response to glucagon was excessive. Glucagon suppression diminished hepatic responsiveness to epinephrine in both models. Stress-induced diabetic instability could relate to exaggerated glucagon release or to increased hepatic sensitivity to glucagon. Thus, during hypoglycemia, exercise, or epinephrine infusion, prevailing plasma insulin levels govern the relative metabolic roles of epinephrine and glucagon.
Somatostatin, glucagon, and insulin secretion from perfused pancreas of BB rats
Authors: Ruggere M. D. , Patel Y. C.
Published: December 2017

We reported previously that pancreatic somatostatin and glucagon content and D and A cells are reduced in spontaneously diabetic BB rats while portal plasma levels of these hormones are elevated but normalized by insulin therapy. Presently, we have characterized the basal and stimulated (glucose, theophylline, arginine) release of islet hormones from perfused pancreases of three groups: nondiabetic, untreated diabetic, and insulin-treated diabetic rats. Maximal glucagon and somatostatin release were significantly reduced in untreated diabetics. Treatment normalized glucagon but further reduced somatostatin secretion. Thus, hyperglucagonemia and hypersomatostatinemia cannot result from pancreatic hypersecretion but are of extrapancreatic (probably gut) origin. A theophylline-induced paradoxical inhibition of somatostatin secretion that was normalized by insulin was found in insulin-openic diabetic rats. This likely represents a secondary effect of insulin deficiency. One animal with the rare finding of spontaneous recovery from insulin-dependent diabetes was characterized as normoglycemic, hypoinsulinemic, hypersomatostatinemic, and normoglucagonemic. Normal basal and hyperglycemic insulin release was exhausted by more potent secretagogues. Somatostatin release was markedly exaggerated, whereas secretagogues had no significant effect on elevated basal glucagon output.
Intrahepatic glucose: a requirement for neonatal ODC induction by specific hormones
Authors: Evoniuk G. , Kuhn C. , Schanberg S.
Published: December 2017

We have shown previously that short-term nutritional deprivation causes a tissue-specific loss of liver ornithine decarboxylase (ODC) induction after isoproterenol, phenylephrine, or glucagon administration in rat pups. To examine the role of nutrition in the regulation of hepatic ODC, we tested the ability of intragastric nutrient administration to reverse nutritionally related deficits in the ODC response to hormonal challenge. Intragastric whole milk was effective in restoring ODC induction and accumulation of its immediate product, putrescine, in response to isoproterenol administration. Glucose was shown to mediate this effect by the ability of intragastric skimmed milk, lactose, galactose, or D-glucose to return ODC induction, and the inability of casein, sucrose, fructose, L-glucose, or pyruvate plus lactate to do so. D-Glucose also reestablished ODC induction by phenylephrine and glucagon. Parenteral administration of D-glucose produced results comparable to those obtained after intragastric administration. Isoproterenol induction of ODC was prevented when hepatic glucose uptake was blocked by phlorizin but not by blockade of central nervous system glucose uptake with 2-deoxyglucose. We conclude that intrahepatic glucose is an absolute requirement for hepatic ODC induction by isoproterenol, phenylephrine, or glucagon in preweanling rats.
Evidence for noncholinergic ganglionic neural stimulation of B cell secretion
Authors: Raghu P. K. , Taborsky G. J. , Paquette T. L. , Halter J. B. , Palmer J. P.
Published: December 2017

Insulin levels increase after 2-deoxyglucose (2DG) administration in dogs. This observation is in contrast to the decrease in insulin level post-2DG in baboons and rabbits. To evaluate a possible neural mechanism mediating this increase in insulin level, we studied normal mongrel dogs with 2DG alone, 2DG during ganglionic blockade, beta-adrenergic blockade, and postganglionic parasympathetic blockade. There was an increase in plasma epinephrine, norepinephrine, pancreatic polypeptide, insulin, and glucose post-2DG alone. During ganglionic blockade, the increase in epinephrine, norepinephrine, and pancreatic polypeptide post-2DG was completely abolished, verifying ganglionic blockade of sympathetic and parasympathetic pathways, respectively. Despite this, ganglionic blockade failed to abolish the insulin rise after 2DG. Postganglionic parasympathetic blockade did not change the insulin rise after 2DG. However, beta-adrenergic blockade completely abolished the insulin rise after 2DG. The above data suggests that 1) the insulin rise post-2DG is beta-adrenergic but 2) the ganglionic neurotransmitter mediating the 2DG-induced insulin rise during ganglionic blockade is noncholinergic (possibly peptidergic).
Beta-adrenergic blockade and training in human subjects: effects on muscle metabolic capacity
Authors: Svedenhag J. , Henriksson J. , Juhlin-Dannfelt A.
Published: December 2017

Sixteen male subjects (20–31 yr) trained for 8 wk on cycle ergometers. Eight of the subjects were treated during the training period with the beta-adrenoceptor blocker propranolol (160 mg/day). During all pre-and posttraining tests, subjects were uninfluenced by the medication. Training-induced increases in VO2max and decreases in blood lactate and norepinephrine concentrations at submaximal exercise were not different between the beta-blockade and the placebo groups. The activities of the mitochondrial enzymes citrate synthase (CS), succinate dehydrogenase (SDH), cytochrome c oxidase (Cyt-c-ox), and 3-hydroxyacyl-CoA dehydrogenase (HAD) in the quadriceps femoris muscle increased significantly (P less than 0.01) with training (beta-blockade group, +47, +33, +38, and 22%; placebo group, +75, 70, +87, and +63%, respectively). Cyt-c-ox and HAD increased significantly more in the placebo group than in the beta-blockade group, while a tendency to an increase was noted for SDH. Muscle capillary density increased similarly (+17–19%) with training in the two groups (P less than 0.01). In conclusion, subjects training under the influence of a therapeutic level of beta-adrenergic blockade show marked increases in both the respiratory capacity and the capillary supply of the engaged skeletal muscles. However, the increase in muscle mitochondrial enzymes may be less apparent than in the normal state.
Effect of thyroid status on K+-stimulated metabolism and 45Ca exchange in rat skeletal muscle
Authors: Van Hardeveld C. , Clausen T.
Published: December 2017

In the perfused hindlimbs of hypo-, eu-, and hyperthyroid rats, high K+o (20 mM) markedly stimulated glucose uptake, lactate production, and O2-consumption to levels increasing with the thyroid status. At Ca2o+ less than 50 microM, all the responses became transient. In the hypothyroid preparations, caffeine (5 mM) produced no stimulation, but in those obtained from eu- and hyperthyroid rats, it increased all the metabolic parameters as well as K+ release in proportion to thyroid status. In isolated soleus and extensor digitorum longus muscles, both high K+o and caffeine stimulated 45Ca-efflux, with the response increasing in proportion to thyroid status. This stimulation was reduced by 70-100% with dantrolene (10(-5) M), which in earlier studies was shown to suppress the metabolic effects of high K+o and caffeine. High K+o also increased 45Ca-influx but produced no change in muscle calcium contents. The results support the idea that thyroid hormones control substrates availability and energy consumption in skeletal muscle by increasing the amount of sarcoplasmic reticulum and thereby the rate of Ca2+ mobilization into the cytosol.
Cerebral oxygen and energy metabolism during and after 30 minutes of moderate hypoxia
Authors: Kintner D. , Fitzpatrick J. H. , Louie J. A. , Gilboe D. D.
Published: December 2017

Sixty-four isolated canine brain preparations were subjected to either 15 or 30 min of perfusion with blood equilibrated at either Pao2 30 mmHg or Pao2 40 mmHg followed by up to 60 min of reoxygenation with blood having a Pao2 greater than 100 mmHg. Pao2 30 mmHg perfusion decreased oxygen availability and the cerebral metabolic rate for oxygen (CMRo2) to 44 and 49% of normal, respectively, whereas Pao2 40 mmHg perfusion decreased oxygen availability and CMRo2 to 64 and 70% of normal, respectively. Creatine phosphate was markedly decreased (0.6 and 4% of normal, respectively) and ATP was only slightly decreased (73 and 90% of normal, respectively) in these preparations during the hypoxic period. Although ATP returned to normal during the reoxygenation period in both groups, creatine phosphate and CMRo2 returned to normal only in the Pao2 40 mmHg preparations. In brains perfused at various Pao2 levels for periods ranging from 6 to 30 min, the total oxygen deficit (the cumulative difference over time between normal and actual CMRo2) rather than tissue lactate levels appeared to influence the restoration of CMRo2 to normal following hypoxia. An oxygen deficit in excess of 25 mumol/g precluded return to a normal CMRo2 following reoxygenation.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of alpha-agonist on renin and prostaglandin E2 release in anesthetized dogs
Authors: Takahashi K. , Hisa H. , Satoh S.
Published: December 2017

The relationship between renin release and renal prostaglandin (PG) production induced by the alpha-agonists methoxamine and alpha-methylnorepinephrine was examined in anesthetized dogs. Both intrarenal infusions of methoxamine (1, 3, and 5 micrograms/min) and alpha-methylnorepinephrine (0.37, 1, and 2 micrograms/min) resulted in a dose-dependent decrease in renal blood flow to a slight degree. Methoxamine dose-dependently increased the renin secretion rate but failed to increase the PGE2 secretion rate. In contrast, alpha-methylnorepinephrine failed to affect the renin secretion rate but dose-dependently increased the PGE2 secretion rate. The effect of methoxamine (5 micrograms/min) on renin release was abolished by the intrarenal alpha 1-adrenoceptor blockade with prazosin (3 micrograms/min) but was not affected by the intrarenal alpha 2-adrenoceptor blockade with yohimbine (30 micrograms/min). The effect of alpha-methylnorepinephrine (2 micrograms/min) on PGE2 release was abolished by yohimbine but not by prazosin. These results suggest that there is a dissociation between renin release and renal PG production induced by alpha-agonists and that renal alpha 1- and alpha 2-adrenoceptors may participate in renin and PGE2 release, respectively.
Defective trophic response of brown adipose tissue of myopathic hamsters
Authors: Triandafillou J. , Hellenbrand W. , Himms-Hagen J.
Published: December 2017

Hamsters with muscular dystrophy (BIO 14.6) have a smaller than normal amount of brown adipose tissue. Two stimuli that promote growth of brown adipose tissue in normal hamsters, short photoperiod and eating a high-fat diet, are here shown to be without effect on brown adipose tissue of myopathic hamsters. Cold-induced growth of brown adipose tissue occurs normally [Am. J. Physiol. 239 (Cell Physiol. 8): C18–C22, 1980]. There is a normal rate of turnover of norepinephrine in brown adipose tissue of the myopathic hamster but a failure of the tissue to hypertrophy in response to norepinephrine is unlikely since norepinephrine does not appear to mediate the trophic response [Am. J. Physiol. 247 (Endocrinol. Metab. 10): E793–E799, 1984]. Denervation results in a marked reduction in size (protein content) of brown adipose tissue of normal hamsters but has very little effect on the size of brown adipose tissue of myopathic hamsters. A central, possibly hypothalamic, defect in the myopathic hamster is postulated to underlie its abnormal control of brown adipose tissue hypertrophy.
Insulin increases thermogenesis in rat skeletal muscle following exercise
Authors: Balon T. W. , Zorzano A. , Goodman M. N. , Ruderman N. B.
Published: December 2017

Insulin increased O2 consumption in isolated perfused rat muscle for upward of 2 h after a treadmill run. Insulin did not increase O2 consumption in nonexercised rats, nor did prior exercise increase O2 consumption in the absence of added insulin. The stimulation of glycogen synthesis by insulin was also enhanced in muscle of previously exercised rats. The additional energy required for this was not sufficient to account for the increase in O2 consumption, however. The results indicate that insulin increases thermogenesis in skeletal muscle after exercise. They also raise the possibility that in intact organisms the thermogenic effect of foods that increase insulin secretion could be increased by prior exercise.
Brown adipose tissue in cafeteria-fed hamsters
Authors: Schimmel R. J. , McCarthy L.
Published: December 2017

Hamsters consuming a “cafeteria diet” had more brown adipose tissue than did chow-fed hamsters. The growth of the brown fat depots in cafeteria-fed hamsters was accompanied by increases in tissue protein and cytochrome oxidase. To assess the thermogenic capacity of brown fat mitochondria, the binding of GDP to isolated mitochondria was measured. Mitochondrial GDP binding was not affected by feeding the cafeteria diet for 4 wk, but more prolonged cafeteria feeding for 8 wk did, however, increase the binding of GDP to isolated mitochondria. The morphology of brown adipose tissue was altered during cafeteria feeding. The brown adipose tissue of cafeteria-fed hamsters had more large unilocular cells than did the brown adipose tissue of chow-fed hamsters. In addition, the average adipocyte diameter was greater in brown adipose tissue of cafeteria-fed hamsters. These data support the presence of a dietary regulation of brown adipose tissue growth in hamsters. The growth of brown adipose tissue in hamsters eating the cafeteria diet appears to result largely from proliferation of adipocytes, as evidenced by the increases in tissue protein and cytochrome oxidase during cafeteria feeding, but some hypertrophy of the adipocytes also occurs. A dietary regulation of brown fat thermogenic capacity is also apparent but this regulation is evident only after more prolonged periods of cafeteria feeding. Hamsters eating a cafeteria diet increase their caloric intake but have the same or greater body weight gain efficiency as do chow-fed animals. The absence of dietary stimulation of thermogenesis may underlie the similar efficiencies of weight gain in chow- and cafeteria-fed hamsters.
Water deprivation upregulates angiotensin II receptors in rat anterior pituitary
Authors: Israel A. , Saavedra J. M. , Plunkett L.
Published: December 2017

Angiotensin II (ANG II) receptors were quantitated in pituitary glands of individual male Long Evans rats by autoradiography after incubation of 8-microns thick pituitary sections with 125I-[Sar1]ANG II. Rat anterior pituitary had a single class of high-affinity saturable ANG II receptors with a Bmax of 1,360 +/- 109 fmol/mg protein and a Ka of 0.510 +/- 0.03 X 10(9) M-1. Five days of water deprivation produced a marked increase in the number of anterior pituitary ANG II receptors (Bmax: 2,428 +/- 233 fmol/mg protein, a 79% increase, P less than 0.001) and a decrease in affinity for the ligand (Ka: 0.337 +/- 0.01 10(9) M-1, a 34% decrease, P less than 0.05). Our results suggest a role for anterior pituitary ANG II receptors in the regulation of fluid and electrolyte metabolism in the rat.
Characterization of aldosterone binding sites in circulating human mononuclear leukocytes
Authors: Armanini D. , Strasser T. , Weber P. C.
Published: December 2017

Aldosterone binding sites in human mononuclear leukocytes were characterized after separation of cells from blood by a Percoll gradient. After washing and resuspension in RPMI-1640 medium, cells were incubated at 37 degrees C for 1 h with different concentrations of [3H]aldosterone plus a 100-fold concentration of RU-26988 (11 alpha, 17 alpha-dihydroxy-17 beta-propynylandrost-1,4,6-trien-3-one), with or without an excess of unlabeled aldosterone. Aldosterone binds to a single class of receptors with an affinity of 2.7 +/- 0.5 nM (means +/- SD, n = 14) and a capacity of 290 +/- 108 sites/cell (n = 14). The specificity data show a hierarchy of affinity of desoxycorticosterone = corticosterone = aldosterone greater than hydrocortisone greater than dexamethasone. The results indicate that mononuclear leukocytes could be useful for studying the physiological significance of these mineralocorticoid receptors and their regulation in humans.
Splanchnic substrate balance in malnourished patients during parenteral nutrition
Authors: Gil K. M. , Gump F. E. , Starker P. M. , Askanazi J. , Elwyn D. H. , Kinney J. M.
Published: December 2017

Twenty-four-hour values for splanchnic substrate balance, O2 consumption, and CO2 production were estimated in nutritionally depleted patients, once while receiving 5% dextrose (D5W) and again after 6 or more days of glucose-based total parenteral nutrition (TPN). Nitrogen balance and whole body gas exchange were also measured. The majority of protein loss during D5W administration and the net protein synthesis during TPN occurred in the periphery. Increases in whole body and splanchnic O2 consumption occurred with TPN administration, but in both cases the splanchnic region accounted for 20% of whole body O2 consumption. Uptake of substrates by the splanchnic region was sufficient to meet splanchnic energy requirements. During TPN infusion uptake by the splanchnic region accounted for 60% of amino acids infused, whereas peripheral uptake accounted for 40%. Splanchnic uptake of glucose accounted for 20% of the glucose infused during TPN. During TPN the splanchnic region took up more glucose and amino acids than was required for energy needs and protein synthesis. It was assumed that the remainder of this substrate was used for lipogenesis. The splanchnic region accounted for 50 +/- 19% of whole body lipogenesis.
Vagal regulation of GRP, gastric somatostatin, and gastrin secretion in vitro
Authors: Nishi S. , Seino Y. , Takemura J. , Ishida H. , Seno M. , Chiba T. , Yanaihara C. , Yanaihara N. , Imura H.
Published: December 2017

The effect of electrical stimulation of the vagus nerves on the release of immunoreactive gastrin-releasing peptide (GRP), gastrin, and somatostatin was investigated using the isolated perfused rat stomach. Electrical stimulation (10 Hz, 1 ms duration, 10 V) of the peripheral end of the subdiaphragmatic vagal trunks produced a significant increase in both GRP and gastrin but a decrease in somatostatin. The infusion of atropine sulfate at a concentration of 10(-5) M augmented GRP release and reversed the decrease in somatostatin release in response to vagal stimulation to an increase above basal levels. However, the gastrin response to vagal stimulation was not affected by atropine. The infusion of hexamethonium bromide at a concentration of 10(-4) M significantly suppressed GRP release but did not affect gastrin secretion in response to vagal stimulation. On the other hand, the somatostatin response to vagal stimulation was completely abolished by hexamethonium. These findings lead us to conclude that the intramural GRP neurons might play an important role in the regulation of gastrin as well as somatostatin secretion and that somatostatin secretion may be controlled not only by a cholinergic inhibitory neuron but also by a noncholinergic, e.g., peptidergic stimulatory neuron, both of which may be regulated through preganglionic vagal fibers via nicotinic receptors. In addition, because the infusion of 10(-7) M GRP suppressed the somatostatin secretion, we suggest that either GRP should be excluded from the list of candidates for the noncholinergic stimulatory neurotransmitter for somatostatin secretion or that there are different mechanisms of action for endogenous and exogenous GRP.
Neonatal adaptation: greater sympathoadrenal response in preterm than full-term fetal sheep at birth
Authors: Padbury J. F. , Polk D. H. , Newnham J. P. , Lam R. W.
Published: December 2017

A marked increase in sympathoadrenal activity at birth has been described in animals and humans. Studies to determine whether the magnitude and duration of the catecholamine surge at birth in preterm lambs is similar to full-term lambs were undertaken using an acutely exteriorized fetal lamb. To maintain a physiologically stable preparation, all preterm lambs were given natural sheep surfactant intratracheally before the first breath. Base-line catecholamine values were similar in the full-term and preterm lambs. After umbilical cord cutting there was a marked increase in circulating norepinephrine (NE) and epinephrine (E) in both full-term and preterm animals. The preterm animals exhibited a delayed but exaggerated elevation of both NE and E relative to term animals. The peak preterm value for NE (3.8 +/- 1.2 ng/ml) occurred at 60 min and exceeded the peak NE value 1.2 ng/ml observed at 15 min in full-term animals. The peak E concentration in preterm animals was over 9 ng/ml between 2 and 3 h of age, whereas full-term animals reached a peak value of 1.1 ng/ml at 5 min. Heart rate and blood pressure rose abruptly to peak values by 5-15 min in full-term animals. Changes in heart rate and mean arterial pressure were less profound and more gradual in preterm animals. Full-term animals also demonstrated a five-to sevenfold increase in plasma free fatty acids, whereas concentrations in preterm animals increased only two- to threefold. There was a similarly blunted response in blood glucose in preterm animals. The catecholamine surge at birth may be an important adaptive phenomenon with physiological implications.
Effect of glucagon on hepatic lactate metabolism in the conscious dog
Authors: Davis M. A. , Williams P. E. , Cherrington A. D.
Published: December 2017

The present experiments were undertaken to assess hepatic lactate metabolism in the overnight-fasted, conscious dog after a physiological elevation in glucagon. Animals were given somatostatin plus intraportal insulin (243 microU . kg-1 . min-1) and glucagon (0.65 ng . kg-1 . min-1) to initially fix the pancreatic hormone levels at basal values. After a 40-min control period the glucagon level was increased to 527 +/- 27 pg/ml, while the insulin level was left unchanged (10 microU/ml). Fifteen minutes later blood lactate had increased by 215 +/- 24 mumol/l because of a marked increase in lactate output by the liver [2.4 +/- 2.0 to 10.0 +/- 3.8 mumol . kg . min (P less than 0.05)]. Subsequently, hepatic lactate output decreased, and after 3 h the liver was taking up lactate at a rate of 3.1 +/- 1.6 mumol . kg-1 . min-1 (P less than 0.05). Gut and renal lactate production were not significantly affected by glucagon. The rate of conversion of lactate and alanine to glucose had tripled after 3 h of hyperglucagonemia, while the efficiency with which the liver converted the incoming gluconeogenic precursors to glucose had doubled. The fractional extraction of alanine by the liver had more than doubled by 3 h, and net hepatic alanine uptake had increased by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
Vascular perfusion: a novel means of studying oviduct function
Authors: Leese H. J. , Gray S. M.
Published: December 2017

An in situ preparation for the combined vascular and luminal perfusion of the rabbit oviduct has been developed. Medium 199, gassed with 5% CO2 in O2 and supplemented with heparin, antibiotics, and 2.5% wt/vol dialyzed bovine serum albumin was infused into the ovarian artery at a rate of 1 ml/min. Krebs Ringer bicarbonate medium was recirculated through the lumen at a rate of 50 microliter/min. The ovary was perfused together with the oviduct, and the preparation is viable for up to 3 h. Equal concentrations of pyruvate, lactate, glucose, and sucrose added to the vascular medium were transported at different rates into the lumen, as was a physiological mixture of amino acids. A proportion of the lactate entering the lumen was synthesized within the oviduct from vascular glucose. When glucose and pyruvate were omitted from the vascular medium, their appearance and that of lactate in the lumen was barely detectable, suggesting that these oviduct fluid components are mainly derived from the blood. The oviduct maintained a steady transmural potential difference of 5.9 mV (lumen negative). With vascular perfusion alone, oviduct fluid entered the oviduct lumen at a rate of 16.8 microliter/h. In oviducts taken from rabbits 3 days postovulation, there was a general decrease in the vascular to lumen flux of all nutrients measured. Preliminary work has shown that the preparation may be used to study ovulation, ovum pickup and transport, and fertilization.
In vivo and in vitro resistance to maximal insulin-stimulated glucose disposal in insulin deficiency
Authors: Dall'Aglio E. , Chang H. , Hollenbeck C. B. , Mondon C. E. , Sims C. , Reaven G. M.
Published: December 2017

The effect of streptozotocin-induced diabetes mellitus on maximal insulin-stimulated glucose uptake in the rat was studied in isolated adipocyte, perfused hindlimb, and the intact organism. Basal glucose transport per fat cell was reduced by approximately two-thirds (P less than 0.001), being associated with a similar decrease in glucose oxidation per fat cell (P less than 0.001). There was also a significant decrease (P less than 0.001) in basal glucose uptake by perfused hindlimb of diabetic rats of approximately 40%. Furthermore, maximal insulin-stimulated glucose transport and oxidation were approximately 50% lower (P less than 0.001) in fat cells of diabetic as compared with control rats. In contrast, maximal insulin-stimulated glucose disposal by perfused hindlimbs from diabetic and control rats was similar, and this was also true of the ability of insulin to maximally stimulate glucose uptake in the intact normal and diabetic rat. These findings indicate that variation exists in the manner in which insulin-sensitive tissues respond to experimentally induced insulin deficiency and support the view that total body glucose disposal is primarily related to insulin action on muscle.
Thermogenesis and BAT activity in hypophysectomized rats with and without corticotropin replacement
Authors: Rothwell N. J. , Stock M. J.
Published: December 2017

Surgical hypophysectomy (Hypox) suppressed body weight, body energy gain, and net energetic efficiency when compared with pair-fed, sham-operated controls but caused marked increases in the thermic response to food, brown adipose tissue (BAT) mass, protein content, and BAT thermogenic activity (estimated from mitochondrial purine nucleotide binding). Chronic replacement of Hypox rats with ACTH restored adrenal weight, plasma corticosterone levels, body energy gain, energetic efficiency, and the thermic response to food to normal. However, the Hypox-replaced animals were apparently fatter (greater carcass energy density) and retained a greater mass of brown fat than controls. Purine nucleotide binding to BAT mitochondria was lower in the ACTH-replaced group than in Hypox rats but remained above the level in controls. These data indicate that hypophysectomy stimulates thermogenesis, probably as a result of decreased adrenal steroid release. However, ACTH does not totally prevent the effects of Hypox, and an involvement of other pituitary hormones and/or hypothalamic-releasing factors cannot be excluded.
Interaction of paraquat and amine uptake by rat lungs perfused in situ
Authors: Rannels D. E. , Pegg A. E. , Clark R. S. , Addison J. L.
Published: December 2017

The kinetics of [14C]paraquat (N,N-di[14C]methyl-4,4'-bipyridylium) uptake from the pulmonary circulation were investigated in rat lungs perfused in situ. During the 1st h of exposure to the herbicide paraquat entered the lungs primarily by diffusion; no evidence was obtained from concentrative uptake, saturation kinetics (1-3,500 microM paraquat), or inhibition by the amines methyl-glyoxal bis(guanylhydrazone) or spermidine, both of which were expected to compete for paraquat transport sites. In contrast, after 60 min of exposure, uptake rates increased two- to three-fold, and paraquat was accumulated to an apparent intracellular concentration greater than that in the perfusate. The latter phase of paraquat uptake was saturable and was inhibited by methylglyoxal bis(guanylhydrazone); it did not appear to reflect a progressive paraquat-induced alteration in cellular permeability but rather predominance of a rapid, carrier-mediated uptake pathway.
Insulin action during fasting and refeeding in rat determined by euglycemic clamp
Authors: Penicaud L. , Kande J. , Le Magnen J. , Girard J. R.
Published: December 2017

To further characterize the role of insulin in glucose metabolism during fasting and refeeding, euglycemic-hyperinsulinemic clamps were performed in control, 3 day-fasted, and 3 day-fasted then 3 day-refed rats. Glucose production and utilization were measured by using [3-3H]glucose. In control and refed rats, hepatic glucose production was totally suppressed at insulin concentration higher than 500 microU/ml; by contrast, during fasting, hepatic glucose production was not suppressed even at insulin concentration tenfold higher. Maximal increment of glucose utilization was lower in fasted than in control rats. Three days of refeeding restored almost entirely normal responses to insulin for glucose utilization. Blood glucose concentration was clamped at a different level in fasted and in control and refed rats; however, increment in glucose clearance in response to insulin was lower in fasted rats than in the two other groups. Thus fasting produces a state of insulin unresponsiveness both at the hepatic and peripheral levels, normal responsiveness being restored after 3 days of refeeding.
Effect of rate of hemorrhage on release of ACTH in cats
Authors: Bereiter D. A. , Zaid A. M. , Gann D. S.
Published: December 2017

The effect of rate of blood loss by acute hemorrhage (H) on adrenocorticotropin (ACTH) and cortisol plasma concentrations was assessed in anesthetized cats. Arterial blood was withdrawn at a rapid rate (10% blood vol/min) or at a slow rate (2%/min), and responses were compared across three volumes of H (10, 20, and 30% of blood vol). After rapid rate of H, ACTH increased in proportion to volume of H (r = 0.669, P less than 0.001) with a mean elevation of 124 +/- 27, 267 +/- 102, and 950 +/- 195 pg/ml for 10, 20, and 30% H, respectively. Slow rate of H evoked a significant increase in ACTH that was not proportional to volume of H (r = 0.314, P greater than 0.10), and the mean change during the post-H sampling period was 611 +/- 166, 828 +/- 302, and 1,070 +/- 239 pg/ml for 10, 20, and 30% H, respectively. Control animals showed no change in ACTH to the repeated sampling paradigm. Rapid H evoked an immediate decrease in mean arterial pressure (MAP) with a post-H recovery of MAP inversely proportionate to volume of H (r = -0.552, P less than 0.01). Slow H caused a progressive decrease in MAP with no significant post-H recovery of MAP at any volume of H. Cortisol concentration increased in proportion to volume of H after rapid H (r = 0.515, P less than 0.025), but not after slow H.(ABSTRACT TRUNCATED AT 250 WORDS)
Pituitary gland: one site of ultrashort-feedback regulation for control of thyrotropin
Authors: Kakita T. , Odell W. D.
Published: December 2017

Studies from our laboratory have previously demonstrated sensitive and specific autoregulatory control systems for thyrotropin (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in the rabbit. Because our studies of LH autoregulation showed the feedback regulation acted directly at a pituitary level, the current studies were designed to investigate whether the TSH control system also acted at the pituitary level. Two species-specific TSH assays were employed; a rabbit TSH radioimmunoassay which showed little or no reaction to human TSH, and a human TSH radioimmunoassay which showed little or no reaction to rabbit TSH. Both in vivo and in vitro studies were performed. TRH (thyrotropin-releasing hormone) in doses of 2, 10, and 50 micrograms was injected as an intravenous bolus into thyroidectomized hypothyroid rabbits during continuous perfusion with highly purified human TSH (hTSH) or with saline. In these in vivo studies, TRH-stimulated rabbit TSH (rTSH) secretion was suppressed by hTSH perfusion compared with control saline perfusion. The effect of hTSH was studied in vitro by employing short-term cultured rabbit pituitary cells. When hTSH was added to the incubation medium, TRH-stimulated rTSH secretion was inhibited. From these studies, we conclude that one site of the autoregulatory control for TSH in the rabbit is at the pituitary level. These studies do not exclude a possible additional short-loop feedback control at an hypothalamic level, but such a site of action is not required to explain the autoregulatory phenomenon.
Effect of angiotensin II, ATP, and ionophore A23187 on potassium efflux in adrenal glomerulosa cells
Authors: Lobo M. V. , Marusic E. T.
Published: December 2017

Angiotensin II stimulus on perifused bovine adrenal glomerulosa cells elicited an increase in 86Rb efflux from cells previously equilibrated with the radioisotope. When 45Ca fluxes were measured under similar conditions, it was observed that Ca and Rb effluxes occurred within the first 30 s of the addition of the hormone and were independent of the presence of external Ca. The 86Rb efflux due to angiotensin II was inhibited by quinine and apamin. The hypothesis that the angiotensin II response is a consequence of an increase in the K permeability of the glomerulosa cell membrane triggered by an increase in cytosolic Ca is supported by the finding that the divalent cation ionophore A23187 also initiated 86Rb or K loss (as measured by an external K electrode). This increased K conductance was also seen with 10(-4) M ATP. Quinine and apamin greatly reduced the effect of ATP or A23187 on 86Rb or K release in adrenal glomerulosa cells. The results suggest that Ca-dependent K channels or carriers are present in the membranes of bovine adrenal glomerulosa cells and are sensitive to hormonal stimulus.
Effects of diets high in refined carbohydrates on renal ammonium excretion in rats
Authors: Preuss H. G. , Fournier R. , Areas J. , Slemmer D.
Published: December 2017

Ammonium excretion was investigated in spontaneously hypertensive rats (SHR) and normotensive control rats (WKY) ingesting different diets. SHR and WKY on low protein-high sucrose diets surprisingly showed the same ammonium excretion as rats ingesting a higher protein-lower sucrose diet. This was unexpected, because ammonium excretion correlates positively with protein intake. The relatively high ammonium excretion despite low protein intake (approximately 40% of control) was not associated with acidosis, hypokalemia, hypocalcemia, and/or hypomagnesemia. In a follow-up study, where diets were high in refined carbohydrates (sucrose, glucose, and starch) but more equal in protein content compared with a diet high in carbohydrates of a more complex form (grains), ammonium excretion increased significantly. When we examined the factors known to influence ammonium excretion, the only significant positive correlations found were between norepinephrine, epinephrine, dopamine, and ammonium excretion. These correlations still remained significant when only the data from the rats on the diets high in refined carbohydrates, i.e., rats on the same dietary intake of minerals and proteins, were compared. In vitro, we corroborated that catecholamines significantly increased ammoniagenesis from kidney slices. Our data show that diets high in refined carbohydrates augment both ammonium and catecholamine excretion and suggest that these two events may be interrelated.
Facultative thermogenesis induced by carbohydrate: a skeletal muscle component mediated by epinephrine
Authors: Astrup A. , Bulow J. , Christensen N. J. , Madsen J. , Quaade F.
Published: December 2017

In addition to the obligatory thermogenesis due to processing and storage, carbohydrate ingestion is accompanied by a facultative thermogenesis mediated by catecholamines via beta-adrenoceptors. The anatomical origin of facultative thermogenesis has hitherto not been determined. The possible involvement of skeletal muscle was examined in lean, healthy subjects by measuring the response in forearm oxygen consumption to an oral glucose load. The study demonstrates an early component of skeletal muscle thermogenesis coinciding with the local glucose uptake, followed by a late facultative thermogenesis. The arterial epinephrine concentration increased to a maximum of 200% above base-line values 4 h after glucose. This value greatly exceeds the physiological threshold for the thermogenic action of epinephrine. In forearm venous blood the corresponding increase in epinephrine was only approximately 50% due to enhanced peripheral extraction, which accompanies an increase in arterial epinephrine levels. Due to venous sampling previous studies have overlooked the magnitude of the late postglucose increase in arterial epinephrine, and its potential thermogenic effect has been disregarded. The facultative thermogenesis in skeletal muscle may be of importance for the regulation of body weight in humans.
A direct growth effect of growth hormone in rat hindlimb shown by arterial infusion
Authors: Schlechter N. L. , Russell S. M. , Greenberg S. , Spencer E. M. , Nicoll C. S.
Published: December 2017

We have developed a method for infusing substances into one hindlimb of the rat via the arterial supply. A catheter attached to an osmotic minipump is inserted into the right superior vesical artery and advanced to the junction of the right common iliac artery. This arrangement permits either constant or pulsatile infusion for 7 days. We employed this method to study the direct action of rat growth hormone (rGH) on the proximal tibial epiphysial plate in hypophysectomized rats. Infusion of neither the solvent nor ovine prolactin (2 micrograms X rat-1 X day -1) affected epiphysial plate width compared with control (uninfused) legs. The rGH infused at 0.4 and 2.0 micrograms X rat-1 X day-1 produced dose-related local growth effects that were of similar magnitude with either constant or pulsatile (eight 1-h pulses/day) infusion. However, the higher dose of rGH also resulted in a systemic effect (i.e., epiphysial plate growth in the uninfused limb), and the pulsatile mode produced a greater systemic effect than that produced by constant infusion. Our results indicate that GH can act directly on cartilage in vivo to maintain growth and that its effectiveness is not enhanced by pulsatile delivery. In contrast, the indirect (i.e., systemic) growth effects of the hormone may be enhanced by intermittent infusion. Our infusion system is well suited for studying the direct effect of substances on hindlimb tissues in conscious, unrestrained rats over extended periods.
Effect of hydrogen ion concentration on corticosteroid secretion
Authors: Radke K. J. , Schneider E. G. , Taylor R. E. , Kramer R. E.
Published: December 2017

The direct effects of changes in extracellular hydrogen ion (H+) concentration on corticosteroid secretion under basal and ACTH-stimulated conditions were studied in isolated, perfused canine adrenal glands. Changes in extracellular H+ concentration were produced by altering either PCO2 or [HCO-3] of the Krebs-bicarbonate perfusate. Alkalosis markedly inhibited ACTH-stimulated aldosterone secretion. Moreover, within the range of pH from 7.19 to 7.85, there was a positive correlation between H+ concentration and the fractional secretion of aldosterone but a negative correlation between H+ concentration and the fractional secretion of corticosterone and 18-hydroxycorticosterone in response to ACTH. In contrast, neither acidosis nor alkalosis had a significant, direct effect on basal or ACTH-stimulated cortisol secretion. We conclude that 1) H+ concentration modulates the stimulatory effect of ACTH on aldosterone secretion by a direct action on the adrenal cortex, 2) acid-base disturbances are specific to the zona glomerulosa of the canine adrenal gland, and 3) H+ concentration may influence events occurring late in the pathway for aldosterone biosynthesis.
A possible role of arachidonate metabolism in the mechanism of prolactin release
Authors: Judd A. M. , Koike K. , MacLeod R. M.
Published: December 2017

The cleavage of arachidonate from pituitary phospholipids may contribute to the process that regulates the release of prolactin. To test this hypothesis, primary cultures of anterior pituitary cells from female rats were preincubated with [3H]arachidonate to label their phospholipid-containing components. The cells were then washed and incubated with vehicle or test agents and the release into the medium of prolactin and [3H]arachidonate cleaved from the phospholipids was measured. Thyrotropin-releasing hormone (TRH) and neurotensin significantly increased the release of both [3H]arachidonate and prolactin. Although basal [3H]arachidonate release was not affected by dopamine or somatostatin, both of these agents reduced [3H]arachidonate release induced by TRH. The relationship between calcium mobilization and arachidonate release was investigated by exposing the cells to agents that modify calcium balance. Maitotoxin, a calcium channel activator, stimulated prolactin and arachidonate release. In contrast cobalt, a calcium channel blocker, penfluridol, a calcium-binding protein inhibitor, and low-calcium medium decreased basal and TRH-induced prolactin release and diminished the TRH-induced release of arachidonate. RHC 80267, an inhibitor of diacylglycerol lipase, decreased TRH-induced prolactin and arachidonate release. BW755c, an inhibitor of the conversion of arachidonate to its metabolites, decreased TRH-induced prolactin release but predictably increased arachidonate release. These findings support the hypothesis that arachidonate metabolites may be involved in the process regulating prolactin release.
Comparison of glucose, LCT, and LCT plus MCT as calorie sources for parenterally nourished septic rats
Authors: Stein T. P. , Fried R. C. , Torosian M. H. , Leskiw M. J. , Schluter M. D. , Settle R. G. , Buzby G. P.
Published: December 2017

Protein and energy metabolism were investigated in acutely septic rats. Rats were made septic by cecal puncture and ligation. For the next 24 h they were given one of five parenteral formulations differing only in the nonprotein calorie source. The five calorie sources were 1) glucose, 2) long-chain triglycerides (LCT), 3) a 27:73 mixture of medium- and long-chain triglycerides (M/LCT), 4) a 50:50 mixture of glucose plus LCT, and 5) a 50:50 mixture of glucose plus the M/LCT mixture. The formulations also contained amino acids at a calorie:ratio of 165:1. The results were that N retention was greater with the glucose plus LCT mixture than with glucose alone. With this mixture, N retention increased as calorie intake increased, whereas with glucose, N retention plateaued. In spite of the high glucose load given to the glucose-only groups, there was a significant reduction in endogenous fat in peripheral depots. Lipid loss was least with the glucose plus LCT combination. The M/LCT mixture given alone or with glucose resulted in significantly lower survival rates.