bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissociation of sympathetic nervous system and adrenal medullary responses
Authors: Young J. B. , Rosa R. M. , Landsberg L.
Published: December 2017

The relative importance of sympathetic nerve (SNS) activity and adrenal medullary secretion in various physiological situations has generally been inferred from measurements of norepinephrine (NE) and epinephrine (E), respectively, in urine or plasma. Increasing evidence, however, indicates that under certain conditions the adrenal medulla may release substantial amounts of NE as well as E. In several of these circumstances, estimates of SNS activity based on the measurement of NE turnover in peripheral tissues of experimental animals indicate diminished SNS function, a reduction that is independent of adrenal medullary secretion. These reciprocal alterations in SNS and adrenal medullary activity fall into two patterns. First, when SNS activity is suppressed by fasting, adrenal medullary responses to various stimuli are enhanced. Second, for certain stimuli the SNS response is biphasic, with an initial suppression followed by subsequent stimulation; during the first phase adrenal medullary secretion is markedly increased. The physiological contribution of the adrenal medulla, therefore, would be particularly important under conditions of SNS suppression.
Effects of glucocorticoids on glutamine metabolism in skeletal muscle
Authors: Muhlbacher F. , Kapadia C. R. , Colpoys M. F. , Smith R. J. , Wilmore D. W.
Published: December 2017

The effects of dexamethasone on nitrogen and amino acid metabolism in the dog were studied in order to gain insight into the role of glucocorticoids in accelerated proteolysis and altered metabolism of glutamine in catabolic illnesses. After dexamethasone administration at a dose of 0.44 mg X day-1 X kg-1, nitrogen balance shifted from slightly positive (+0.126 g N X day-1 X kg-1) to markedly negative (-0.278 g N X day-1 X kg-1). This was associated with a 23% fall in total free amino acid nitrogen in skeletal muscle, with 80% of the decline accounted for by a decrease in glutamine. Plasma glutamine concentration decreased by 26%, although total plasma free amino acid nitrogen was unchanged because of a 49% increase in alanine. The alterations in intracellular and circulating levels of glutamine were not accompanied by measurable changes in glutamine synthetase or glutaminase activities in skeletal muscle. Hindquarter amino acid flux measurements demonstrated that the decline in intracellular glutamine concentration was associated with a marked increase in glutamine efflux from skeletal muscle. This occurred in spite of minimal changes in the intracellular/extracellular glutamine gradient. It is concluded that accelerated muscle glutamine release caused by glucocorticoids is a major contributor to the decreased glutamine levels in muscle that occur during critical illnesses.
Metabolism of round spermatids: evidence that lactate is preferred substrate
Authors: Nakamura M. , Okinaga S. , Arai K.
Published: December 2017

Glucose was utilized at a rate of 17.9 +/- 1.0 nmol X 10(6) cells-1 X h-1, with 5.2 and 9.5% accumulated as glucose and fructose 1,6-diphosphate, respectively, 79.6% transformed into lactate, 2% oxidized by the trichloroacetic acid cycle, and little metabolized by the pentose cycle. Glucose utilization increased and reached a maximum at 1 mM glucose. The ATP level was maintained by approximately 0.8 mM lactate, but not by glucose or pyruvate. Glucose decreased the ATP level to a value lower than the control level due partly to the fructose 6-phosphate-fructose 1,6-diphosphate futile cycle. In the presence of lactate (0.01-20 mM), pyruvate production was increased, but the intracellular level of pyruvate (0.2-0.3 mM) remained unchanged. Lactate dehydrogenase (LDH) activity was increased, at a maximum rate, by 0.1-0.2 mM pyruvate but was inhibited beyond 0.3 mM (Ki = 2.5 mM). The Km values of LDH for pyruvate and lactate were 24.4 +/- 4.2 microM and 2.36 +/- 0.14 mM, respectively. The importance of LDH in glucose and lactate metabolism by spermatids was described. These observations further support the hypothesis that lactate is the preferred substrate for spermatid metabolism.
Neonatal gonadal hormones and blood pressure in the spontaneously hypertensive rat
Authors: Cambotti L. J. , Cole F. E. , Gerall A. A. , Frohlich E. D. , MacPhee A. A.
Published: December 2017

In rats, gonadal steroid hormones present during the neonatal period produce permanent or "organizational" effects that play a role in the sexual differentiation of the brain and sexually dimorphic patterns of behavior. Because there exists a sexually dimorphic pattern in the development of hypertension in the spontaneously hypertensive rat (SHR), we examined the influence of neonatal gonadal hormones on arterial pressure and body weight in these rats. Male SHR rats were castrated or sham-operated (controls) on their day of birth. Female rats received 1.25 mg testosterone propionate (TP) or sesame oil vehicle on their 2nd day of life. Sham-operated males and TP and oil females were gonadectomized at 81 days of age. To examine the transient or "activational" effects of gonadal steroid hormones, testosterone implants were placed subcutaneously in all rats at 128 days of age and were removed at 170 days of age. The rats were killed at 202 days of age, and selected organ weights were determined. During the original treatment, days 44-79, blood pressure in castrated males was comparable to that of control females, whereas blood pressure in neonatal TP females was not different from that of control males. When exposed to testosterone in adulthood, blood pressure increased more in neonatal TP female rats than in control females. Partial correlation analysis indicated that differences in body weights among the groups could not account for their variances in blood pressure. These data suggest that the neonatal gonadal hormone milieu contributes significantly to the sexually dimorphic pattern of hypertension development in the SHR.
Increased leucine flux in short-term fasted human subjects: evidence for increased proteolysis
Authors: Tsalikian E. , Howard C. , Gerich J. E. , Haymond M. W.
Published: December 2017

Plasma leucine concentration increases with short-term fasting in normal humans. In previous studies using an 18-h constant infusion of [2H3]leucine, a 15% decrease in the rate of appearance (Ra) of leucine was observed between 15 and 30 h of fasting. However, incorporation of labeled leucine into and subsequent release from body protein could result in an apparent decrease in leucine Ra. The present studies were undertaken to determine the rate of leucine N and carbon flux in short-term fasted human subjects in using an experimental design that would minimize potential recycling of label. Six normal subjects were infused with [15N]- and [2H3]leucine for two 4-h periods (0600 to 1000 h and 2000 to 2400 h) during a 30-h fast. Between the 15th and 30th h of fasting, plasma leucine concentration (102 +/- 10 to 169 +/- 18 microM, P less than 0.01) and leucine C (1.46 +/- 0.05 to 1.64 +/- 0.10 mumol X kg-1 X min-1, P less than 0.05) and leucine N (1.93 +/- 0.14 to 2.49 +/- 0.26 mumol X kg-1 X min-1, P less than 0.05) flux increased, whereas the metabolic clearance rates of leucine C and N decreased (P less than 0.01 and less than 0.05, respectively). Therefore, when isotope recycling is minimized with short periods of isotope infusion, leucine flux increases between 15 and 30 h of fasting. Because the only source of leucine in the postabsorptive periods is body protein, we conclude that the rate of whole-body proteolysis is increased in short-term fasting in humans.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of a mixed meal on hepatic lactate and gluconeogenic precursor metabolism in dogs
Authors: Davis M. A. , Williams P. E. , Cherrington A. D.
Published: December 2017

The present experiments were undertaken to assess lactate and gluconeogenic precursor metabolism in the 30 h following consumption of a mixed meal by the overnight-fasted, conscious dog. The arterial glucose level rose by a maximum of 13 mg/dl 4 h after the meal and had returned to control levels by 12 h. Hepatic glucose production was suppressed for 12 h after feeding, but net hepatic glucose uptake did not occur. The arterial lactate level rose from 0.55 +/- 0.10 to 1.28 +/- 0.14 mM within 1 h of feeding and remained elevated for 12 h. Net hepatic lactate production, measured with an A-V difference technique, rose from 3.5 +/- 2.8 to 19.4 +/- 3.1 mumol X kg-1 X min-1 h after the meal and declined slowly over the next 22 h. The liver then began to consume lactate so that at 30 h net hepatic uptake was 5.7 +/- 0.5 mumol X kg-1 X min-1. The total hepatic uptake of the gluconeogenic amino acids (alanine, glycine, serine, threonine) increased from 5.3 +/- 0.8 to 11.5 +/- 2.5 mumol X kg-1 X min-1 at 1 h and remained elevated for 4 h. The arterial alanine level rose from 0.36 +/- 0.03 to 0.51 +/- 0.04 mM at 2 h and remained elevated for 18 h. Insulin increased from 11 +/- 2 microU/ml to a maximum of 44 +/- 5 4 h after the meal, and the glucagon level rose from 59 +/- 8 pg/ml to a maximum of 150 +/- 22 1 h after feeding.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of adrenalectomy on activation of glycogen phosphorylase in rat myocardium
Authors: Reese J. B. , Mayer S. E. , Brunton L. L.
Published: December 2017

Adrenalectomy causes a depressed glycogenolytic response to catecholamines in myocardium. Total phosphorylase activity (a + b) is 20% lower in isolated, perfused hearts from adrenalectomized (ADX) rats compared with hearts from sham-operated (sham) rats even though the basal activity ratios (-AMP/+AMP) do not differ. In response to epinephrine (50 nM), the sham group has a higher activity ratio than the ADX group (0.23 vs. 0.16); the difference in specific activities of phosphorylase a in the two groups is even greater, 87 versus 49 U/mg protein. The glycogen content of the heart is 30% lower in the ADX group. Adrenalectomy does not alter the accumulation of cAMP and activation of cAMP-dependent protein kinase caused by epinephrine. Although rat heart contains a heat-stable phosphatase inhibitor, the activity of this inhibitor, as judged by phosphorylase phosphatase activity, is not altered by epinephrine stimulation or by adrenalectomy. Epinephrine perfusion increases the activity ratios (pH 6.8:8.2) of phosphorylase kinase equally in sham and ADX hearts; however, the specific activities of phosphorylase kinase (basal and hormone-stimulated) at either pH are lower after adrenalectomy. The sensitivity of phosphorylase kinase activity to stimulation by calcium is the same in the sham and ADX groups. A radioimmunoassay for phosphorylase kinase detects 10% less of this enzyme in hearts from adrenalectomized animals. Specific activities at pH 6.8 and 8.2 based on the quantity of phosphorylase kinase detected by radioimmunoassay suggest a lower phosphorylation state in the ADX group. Decreases in quantities of phosphorylase and phosphorylase kinase and enzyme dissociation due to glycogen depletion could all contribute to a depressed glycogenolytic response in the ADX group.
Accommodation to a reduced islet cell mass in dogs
Authors: Marincola F. , Cobb L. F. , Horaguchi A. , Maeda M. , Merrell R.
Published: December 2017

The quantitative insulin response to glucose stimulus can be drastically reduced by subtotal pancreatectomy. An 80% pancreatectomy was performed preserving the pancreatic duct in seven dogs. The insulin output into the portal vein and cephalic vein insulin after intravenous glucose challenge were measured. Output was recorded in 25 controls, and before and 2 wk after subtotal pancreatectomy in the seven animals. Histologic sections of the original resection were compared with the remnant of pancreas taken at the end of the study. In this model, which approaches islet cell failure in terms of glucose homeostasis, the tactics that permit enhancement of islet function can be discerned and to some degree quantitated. The pancreatic remnant does not oversecrete to approximate normal function, although glucose sensitivity is somewhat enhanced. No beta-cell hyperplasia was seen. Despite low insulin output into the portal vein, systemic insulin levels are conserved. This decrease in the plasma clearance of insulin supports glucose homeostasis. Accommodation to severe islet reduction occurs via both intrapancreatic and, more importantly, extrapancreatic mechanisms.
Diabetes-induced alterations of glucose metabolism in rat cerebral microvessels
Authors: McCall A. L. , Gould J. B. , Ruderman N. B.
Published: December 2017

The effect of diabetes on the metabolism of glucose and lactate was examined in isolated rat cerebral microvessels. In rats with diabetes induced with streptozotocin, glucose oxidation to CO2 by the microvessels was decreased by 54-83% and its conversion to lactate by 21-61%. Insulin therapy for several days or starvation for 48 h both lowered blood glucose levels in the diabetic rats and restored microvessel glucose metabolism to normal. Cerebral microvessels consist principally of the capillaries that constitute the blood-brain barrier. Direct assessment of the blood-brain barrier in vivo using the brain uptake index (BUI) technique revealed a close parallel to the findings in the microvessels. Thus, hexose transport was diminished in diabetic rats and restored to normal by both insulin therapy and starvation. The oxidation of [1-14C]lactate to CO2 like that of glucose was depressed in microvessels of diabetic rats. In contrast to glucose, however, the transport of lactate across the blood-brain barrier in vivo was not altered. These findings suggest that diabetes suppresses glucose metabolism in rat cerebral microvessels and downregulates glucose transport across the blood-brain barrier. They also suggest that both of these processes are regulated by chronic alterations in blood glucose concentration rather than by insulin per se.
Uterine blood flow and substrate uptake in conscious rabbit during late gestation
Authors: Gilbert M. , Hauguel S. , Bouisset M.
Published: December 2017

The aim of this study was the quantitation of the metabolic demands of the uterus in rabbits between days 24 and 30 of gestation, a time at which there is a fourfold increase in fetal weight. Serial measurements of substrate concentrations in maternal artery and uterine vein were performed over this period. Uterine blood flow was measured on days 24 and 30. Uterine substrate uptake was calculated by application of the Fick principle. Over the gestation range studied, the absolute uterine blood flow increased proportionally to the uterine weight gain. The uterine arteriovenous differences for glucose (G), lactate (L), free fatty acids (FFA), ketone bodies (KB), and oxygen (O2) were constant throughout the study. At both gestational ages, the weight-specific uterine substrate consumption (G, FFA, KB, O2) and production (L) were respectively similar. On days 24 and 30 the amount of G directed to the gravid uterus represented approximately 13 and approximately 36% of the maternal glucose turnover rate, respectively. The maximum contributions of G and FFA to the uterine oxygen consumption on day 24 were 80 and 30%, respectively. We have thus confirmed that at term the gravid uterus is a site of high glucose consumption. Finally, we demonstrated that in a nonruminant species, FFA would be a substantial source of carbon.
Androgen cytosol binding in exercise-induced sparing of muscle atrophy
Authors: Hickson R. C. , Kurowski T. T. , Capaccio J. A. , Chatterton R. T.
Published: December 2017

This study was undertaken to determine whether the exercise-induced sparing of glucocorticoid-induced muscle atrophy is related to increased androgen cytosol binding. Female rats were divided into a sedentary or an exercise group that was trained by treadmill running 100 min/day for 13-15 wk. During the last 12 days of training, each of these groups was further subdivided into groups that received daily subcutaneous injections of cortisone acetate (CA) (100 mg/kg body wt) or the vehicle 1% carboxymethyl cellulose. Exercise prevented 30-40% of the weight loss due to CA treatment in gastrocnemius and plantaris muscles. Scatchard analyses of specific binding of [3H]methyltrienolone (R1881), a synthetic androgen that binds to androgen receptors, were nonlinear in muscles from vehicle-treated sedentary and trained rats and were resolved by a two-component binding model. The lower affinity component, which was attributed to a glucocorticoid receptor, disappeared in muscles of glucocorticoid-treated animals as evidenced by linear Scatchard plots. Receptor concentrations of the androgenic component of [3H]methyltrienolone binding were similar in gastrocnemius and plantaris muscles in all treatment groups. In binding specificity studies of gastrocnemius muscles, the relatively high competition by various glucocorticoids and progesterone for [3H]methyltrienolone binding in the vehicle-treated groups was reduced by CA treatment. The lack of change in androgen cytosol receptor levels suggests that this is not a mechanism by which exercise protects against glucocorticoid-induced muscle atrophy.
Insulin resistance of denervated rat muscle: a model for impaired receptor-function coupling
Authors: Burant C. F. , Lemmon S. K. , Treutelaar M. K. , Buse M. G.
Published: December 2017

The effect of short-term denervation on the response to insulin was studied in isolated rat soleus and extensor digitorum longus (EDL) muscles 6 and 24 h after severing one sciatic nerve. Impaired insulin sensitivity and response occurred within 6 h postdenervation in solei. After 24 h, EDL of fed and fasted rats and solei of fed rats showed no stimulation of glycogen synthesis even with supraphysiological doses, whereas solei of fasted rats showed markedly decreased sensitivity and response to insulin. Insulin resistance of glycogen synthesis represented impaired stimulation of glucose transport and impaired glucose-independent activation of glycogen synthase by insulin. Changes in initial glycogen content of muscles did not correlate with insulin resistance. Insulin binding after denervation showed only minimum impairment and did not account for the marked insulin resistance. The response of denervated solei to epinephrine was unimpaired. Insulin resistance, which develops early after denervation in red and white muscles, represents primarily a defect in receptor-function coupling, suggesting that in muscle, nervous stimuli and/or contractile activity modulate signal transmission by the occupied insulin receptor.
Kinetics of cell age-dependent decline of insulin receptors in human red cells
Authors: Baumann G. , MacCart J. G.
Published: December 2017

Insulin receptors are present in human erythrocytes and correlate negatively with cellular age. Little is known about the function of these receptors, about the precise kinetics of their decline during cell aging or about their fate after disappearance from the cells. To elucidate some of these questions, we have prepared red blood cell populations of widely varying cellular ages (ranging from the erythroblast stage to senescent mature erythrocytes) by isopycnic centrifugation on isosmolar density gradients. In addition, young red cells were cultured for 4 days in vitro to permit observation of short-term changes. In mature erythrocytes, insulin receptors decreased as an exponential function of cell age with an estimated half time of 40 days. A more rapid decline of insulin receptors occurred coincident with reticulocyte maturation. Loss of receptors from cultured cells was accompanied by appearance of a soluble insulin receptor in the medium. The effect of insulin on glucose utilization in erythroblast and reticulocyte preparations was negligible, as assessed by CO2 and lactate production. We conclude that 1) insulin receptors are progressively lost from the red blood cell after the erythroblast stage; 2) receptor loss is particularly rapid during reticulocyte maturation; 3) shedding of receptors into the extracellular environment is one reason for their depletion from cells; and 4) in basophilic erythroblasts and reticulocytes, insulin exhibits little metabolic action despite the relatively high receptor complement present in these cells.
Abnormal coupling of insulin receptor binding in noninsulin-dependent diabetes
Authors: Mandarino L. J. , Campbell P. J. , Gottesman I. S. , Gerich J. E.
Published: December 2017

By use of the glucose clamp sequential insulin infusion technique, we compared the dose-response characteristics of insulin-mediated glucose disposal in 17 patients with noninsulin-dependent diabetes mellitus (NIDDM) and 13 age- and weight-matched nondiabetic volunteers. In terms of plasma insulin concentrations, the dose-response curve in the diabetics was shifted to the right (Km 156 +/- 28 vs. 58 +/- 4 microU/ml in nondiabetics, P less than 0.01) with a decreased maximum response (Vmax 320 +/- 22 vs. 405 +/- 10 mg X m-2 X min-1 in nondiabetics, P less than 0.01). Moreover, coupling between insulin receptor binding and activation of insulin effector units was defective in the diabetic subjects (half-maximally effective insulin receptor occupancy 184 +/- 11 vs. 145 +/- 12 pg in nondiabetics for monocytes, P less than 0.02, and 120 +/- 8 vs. 85 +/- 4 pg for erythrocytes in nondiabetics, P less than 0.01). The presence of defective coupling in itself could explain the abnormal insulin dose-response characteristics for glucose disposal in NIDDM and differentiates the insulin resistance of this condition from that of obesity in which coupling is normal.
Dopamine may be a neurohormone in rat adrenal cortex
Authors: McCarty R. , Kirby R. F. , Carey R. M.
Published: December 2017

In the periphery, dopamine (DA) is a precursor for norepinephrine (NE) and epinephrine (EPI) biosynthesis and is itself a neurotransmitter in sympathetic ganglia. In addition, DA may function as a neurohormone in providing maximum tonic inhibition of aldosterone secretion from the adrenal cortex. We have quantified the catecholamine content of the adrenal gland and have examined factors that regulate DA content of the adrenal cortex. Adult male Sprague-Dawley rats were assigned to one of four groups: adrenal demedullated (ADM); adrenal denervated via splanchnic nerve section (ADN); adrenal demedullated-denervated (DMN); and sham-operated controls (Sham). Ten days after surgery, rats were killed by decapitation, and the adrenals were removed and later assayed for catecholamine content. Compared with Sham, ADM and DMN decreased NE and EPI levels by 92–99% but DA levels by only 57–58%. ADN decreased levels of each catecholamine by 18–26%. These findings indicate that the adrenal cortex contains approximately 40% of the total gland content of DA and less than 8% of the total gland content of NE and EPI. Furthermore, DA in the adrenal cortex does not appear to require an intact splanchnic nerve supply to the adrenal. In a second experiment, we examined the effects of inhibition of catecholamine biosynthesis with alpha-methyl-p-tyrosine (alpha-MPT) on DA content in Sham and ADM rats. In Sham rats, alpha-MPT decreased adrenal DA by 44% and heart NE by 37%. In contrast, treatment of ADM rats with alpha-MPT increased adrenal DA by 49% but decreased heart NE by 36%.(ABSTRACT TRUNCATED AT 250 WORDS)
Synergistic effects of oPL and insulin on glycogen metabolism in fetal rat hepatocytes
Authors: Freemark M. , Handwerger S.
Published: December 2017

The interactions between ovine placental lactogen (oPL) and insulin in the regulation of fetal liver glycogen metabolism have been studied in cultured hepatocytes from fetal rats on day 20 of gestation. Both oPL (0.75–22.5 micrograms/ml) and insulin (0.01–1 microM) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen. However, the dose-response curves for the two hormones were not parallel and the maximum effect of oPL was 3.4 times greater than that of insulin (P less than 0.001). The two hormones had synergistic effects on [14C]glucose incorporation at low concentrations and additive effects at maximum concentrations. Ovine growth hormone (oGH) also stimulated [14C]glucose incorporation into glycogen but with a potency only 12.3% that of oPL. Cycloheximide (20 microM) abolished the stimulation of [14C]glucose incorporation by insulin (1 microM), oPL (5 micrograms/ml), and oGH (100 micrograms/ml). Although the glycogenic actions of oPL and insulin may depend on new protein synthesis, the results of these studies suggest that these hormones stimulate glycogen synthesis in fetal liver by different mechanisms. Because the glycogenic actions of oPL are potentiated by insulin, these hormones may act in concert to promote hepatic glycogen storage in the fetus.
Glycogen repletion in different skeletal muscles from diabetic rats
Authors: Hamilton N. , Noble E. G. , Ianuzzo C. D.
Published: December 2017

It was hypothesized that chronically untreated streptozotocin-diabetic rats may compensate for the detrimental effect of insulin deficiency on glycogen restoration following muscular work. Glycogen concentration ([GLY]) was reduced by in situ stimulation of the sciatic nerve of anesthetized normal (N) and diabetic (D) Sprague-Dawley albino rats. Glycogen repletion occurred most rapidly within 30 min after stimulation. By 2 h all N muscles returned to basal [GLY]. D muscles repleted glycogen at a rate 45–75% of normal and not all of the D muscle returned to basal [GLY] by 8 h poststimulation. Neither the partial reduction in diabetic hyperglycemia by using phlorizin nor the acute further lowering of diabetic hypoinsulinemia by using insulin antibody affected glycogen restoration in D muscles. Acute insulin replenishment resulted in restoration of normal [GLY] in D muscles within 2 h poststimulation. These findings are not consistent with the proposed hypothesis and indicate insulin is necessary to have normal rates of glycogen restoration following muscular activity.
Coenzyme A metabolism
Authors: Robishaw J. D. , Neely J. R.
Published: December 2017

The metabolism of coenzyme A and control of its synthesis are reviewed. Pantothenate kinase is an important rate-controlling enzyme in the synthetic pathway of all tissues studied and appears to catalyze the flux-generating reaction of the pathway in cardiac muscle. This enzyme is strongly inhibited by coenzyme A and all of its acyl esters. The cytosolic concentrations of coenzyme A and acetyl coenzyme A in both liver and heart are high enough to totally inhibit pantothenate kinase under all conditions. Free carnitine, but not acetyl carnitine, deinhibits the coenzyme A-inhibited enzyme. Carnitine alone does not increase enzyme activity. Thus changes in the acetyl carnitine-to-carnitine ratio that occur with nutritional states provides a mechanism for regulation of coenzyme A synthetic rates. Changes in the rate of coenzyme A synthesis in liver and heart occurs with fasting, refeeding, and diabetes and in heart muscle with hypertrophy. The pathway and regulation of coenzyme A degradation are not understood.
Regulation of plasma lipid levels by plasma viscosity in nephrotic rats
Authors: Yedgar S. , Eilam O. , Shafrir E.
Published: December 2017

The viscosity of the extracellular medium of cultured hepatocytes has been shown to be a regulator of the secretion and synthesis of very low-density lipoproteins (Yedgar et al., J. Biol. Chem. 257: 2188-2192, 1982). At present, the role of plasma viscosity in regulation of plasma lipoprotein levels was examined in vivo using nephrotic hyperlipidemic rats. Plasma viscosity was increased by injection of macromolecules: simultaneously with induction of nephrosis by aminonucleoside; and after the lipid level had reached its maximum. In experiment 1 the elevation of plasma viscosity (which persisted for at least 2 days) delayed the development of the hyperlipidemia by at least 2 days. In experiment 2 increasing the plasma viscosity reduced plasma triglyceride and cholesterol levels by 70 and 40%, respectively, within 2 days. The hyperlipidemia was accompanied by increased plasma viscosity. The contribution of lipoproteins to plasma viscosity was 27% in the nephrotic-hyperlipidemic rats, compared with 4% in normal rats. It is suggested that plasma viscosity regulates lipoprotein levels in vivo concordant with the observation in cultured hepatocytes.
Reserpine is a calcium channel antagonist in normal and GH3 rat pituitary cells
Authors: Login I. S. , Judd A. M. , Cronin M. J. , Yasumoto T. , MacLeod R. M.
Published: December 2017

Reserpine exerts direct effects on several tissues, including inhibition of hormone release from rat anterior pituitary cells. To test the hypothesis that reserpine may be acting as a calcium channel antagonist, normal or GH3 rat anterior pituitary cells were preincubated in reserpine or the conventional calcium channel blocker, D-600, followed by exposure to 45Ca2+ together with stimulants of calcium uptake: maitotoxin, a potent calcium channel activator; A23187, a calcium ionophore; or 50 mMK+. After incubation, the cells were harvested by vacuum filtration and cell-associated radioactivity determined. In normal cells, reserpine blocked both basal and K+-stimulated calcium uptake. Reserpine selectively blocked maitotoxin but not A23187-induced calcium uptake. In GH3 cells 9 microM reserpine and 30 microM D-600 were equally effective in blocking maitotoxin-stimulated calcium uptake. Reserpine appears to block voltage-dependent calcium channels in pituitary cells in a concentration-dependent manner but not calcium uptake caused nonspecifically by A23187.
Palatability and postprandial thermogenesis in dogs
Authors: Diamond P. , Brondel L. , LeBlanc J.
Published: December 2017

The role of palatability on postprandial thermogenesis was determined in six mongrel dogs of approximately 16 kg. Oxygen uptake (VO2) was continuously monitored by indirect calorimetry for 1 h before and 2 h after a standard meal of 1,390 kcal. In the first experiment each dog was given access to the meal, which was ingested within 5 min. In a second experiment the same meal was sham fed and collected into an esophageal pouch. In a third experiment the dogs were tube fed. In the first experiment a biphasic response was found in the postprandial increase in metabolic rate; a first phase lasting approximately 40 min and the other from 40 to 125 min. In the second experiment the increase in VO2 was comparable with that of the first experiment for the first 40 min but almost abolished for the remaining period; the sight and smell of food alone produced a similar effect. In the third experiment tube feeding caused a small increase in VO2, which was four times smaller than that found in both the first and the second experiment during the initial phase. However, during the second phase the increase in VO2 was comparable with that of experiment 1. An initial phase of feeding lasting approximately 40 min is identified with food palatability, whereas the second phase would correspond to a large extent to specific dynamic action of food.
Pentobarbital effects on plasma catecholamines: temperature, heart rate, and blood pressure
Authors: Baum D. , Halter J. B. , Taborsky G. J. , Porte D.
Published: December 2017

The effects of intravenous pentobarbital were studied in dogs. Plasma pentobarbital concentrations were inversely related to epinephrine and norepinephrine concentrations. Plasma catecholamines appeared fully suppressed at pentobarbital levels greater than 25-30 micrograms/ml. Furthermore, pentobarbital levels were negatively related to rectal temperature, heart rate, and mean blood pressure. The methods of pentobarbital administration influenced plasma pentobarbital as well as epinephrine and norepinephrine levels, temperature, heart rate, and blood pressure. These observations suggest the possibility that pentobarbital inhibits the sympathetic nervous system, which in turn may affect temperature, heart rate, and blood pressure. Because pentobarbital anesthesia affects plasma catecholamine concentrations, the regimen used in animal models requires consideration when interpreting data potentially influenced by the sympathetic nervous system.
Role of hepatocyte plasma membrane in insulin degradation
Authors: Blackard W. G. , Ludeman C. , Stillman J.
Published: December 2017

An important role of the cell membrane in insulin degradation by cultured rat hepatocytes is supported by studies using the surface-active antibiotic bacitracin. Bacitracin inhibited degradation of cell-associated insulin (both randomly and A14 labeled) by 80–90% at 15 degrees C and by 60% at 37 degrees C. At 37 degrees C, inhibition of degradation was observed only with bacitracin present during dissociation and was accompanied by a compensatory increase in release of trichloroacetic acid (TCA)-precipitable insulin. This profile suggests inhibition of insulin degradation on the membrane after either primary binding or diacytosis (endocytosis-reverse endocytosis). In contrast, at 15 degrees C, bacitracin's inhibitory effect was greater with the antibiotic present during association and was not accompanied by a compensatory increase in TCA-precipitable insulin. This profile was compatible with inhibition of partial cleavage of insulin on the membrane. Internalization and degradation through chloroquine-sensitive pathways may be required to complete degradation at this temperature because chloroquine exhibited an inhibitory effect on insulin degradation equally potent to that of bacitracin at 15 degrees C (no effect at 37 degrees C).
Inhibition of hexose transport in adipocytes by dexamethasone: role of protein synthesis
Authors: Carter-Su C. , Okamoto K.
Published: December 2017

The ability of the synthetic glucocorticoid, dexamethasone, to alter 3-O-methylglucose transport was investigated using isolated rat adipocytes. A maximally effective dose of dexamethasone (10(-7) M) inhibited transport up to 80% within 60–90 min. Inhibition of transport was evident as early as 15–30 min after addition of steroid, and was prevented by both actinomycin D and cycloheximide. When added within 45 or 60 min after dexamethasone, actinomycin D interfered with the cells' ability to respond to the steroid but had no effect when added between 60 and 90 min or longer after the steroid. Cycloheximide interfered with steroid-induced inhibition of transport when added at any time before the 15- to 30-min period immediately preceding the transport assay. This interference with hormone action appeared to be independent of the length of time cells were exposed to dexamethasone before addition of cycloheximide. Thus cells that were maximally inhibited by dexamethasone by 90 min became only partially inhibited when cycloheximide was added at 90 or 120 min, and cells were incubated for an additional 60 or 30 min, respectively. These findings are consistent with the following: dexamethasone inhibits glucose oxidation as a result of inhibiting hexose transport; inhibition of transport by dexamethasone requires the synthesis of RNA during the first 45–60 min after steroid addition and requires protein synthesis during the entire incubation period with dexamethasone; and transport is inhibited within minutes after protein synthesis is initiated.
Androgens in male rat reproductive tract fluids: hypophysectomy and steroid replacement
Authors: Turner T. T. , Ewing L. L. , Jones C. E. , Howards S. S. , Zegeye B.
Published: December 2017

The control of androgen concentrations in the intraluminal fluids of the male reproductive tract is not well understood. The present experiments were performed to determine the effects of hypophysectomy, hypophysectomy plus testosterone (T), and hypophysectomy plus pregnenolone treatment on intraluminal androgen concentrations in the adult rat testis and epididymis. T and 5 alpha-dihydrotestosterone (DHT) concentrations were determined in the vascular, interstitial, and intraluminal compartments of the epididymis. Testicular and epididymal morphology also were examined under light microscopy. Hypophysectomy of at least 5 days duration significantly reduced T and DHT concentrations in serum, tissues, and intraluminal fluids of the reproductive tract. T replacement for 14 days, which produced peripheral T concentrations of 5 ng/ml, did not support intraluminal androgen concentrations in the seminiferous tubules equivalent to controls; rete testis androgen concentrations were similar to controls, however. Pregnenolone administration at 2 mg X rat-1 X day-1 for 14 days did not maintain spermatogenesis nor intraluminal T concentrations in the seminiferous tubules equivalent to controls; however, a low level of spermatogenesis continued when intraluminal and tissue androgen concentrations were maintained at 10-20% of controls by either the testosterone and pregnenolone treatments.
Muscle protein turnover: effects of exercise training and renal insufficiency
Authors: Davis T. A. , Karl I. E. , Tegtmeyer E. D. , Osborne D. F. , Klahr S. , Harter H. R.
Published: December 2017

Chronic renal failure is associated with an enhanced catabolism of muscle protein. To determine the effect of exercise training and moderate renal insufficiency on net protein catabolism and protein synthesis in isolated epitrochlearis muscles, three-fourth nephrectomized and control rats were exercise trained or remained sedentary. Net muscle protein degradation was determined by measuring the rates of release of phenylalanine and tyrosine. Protein synthesis was determined by measuring the incorporation of [U-14C]phenylalanine into muscle protein. Exercise training reduced the elevated protein degradation of uremia to control levels. In control rats, exercise training had no effect on protein degradation. Exercise training increased alanine release in control rats but did not further increase the elevated alanine release of uremia. Protein synthesis was unaffected by both uremia and exercise training. Exercise training in control and uremic rats moderately increased the responsiveness of muscle to insulin by reducing net protein degradation but did not further enhance the insulin-stimulated increase in protein synthesis. Thus exercise training ameliorates the enhanced muscle protein degradation of moderate renal insufficiency.
Dose-response curves for in vivo insulin sensitivity in individual tissues in rats
Authors: Kraegen E. W. , James D. E. , Jenkins A. B. , Chisholm D. J.
Published: December 2017

A technique is described for examining in vivo insulin action on glucose utilization in individual tissues in the intact conscious rat. Indices of tissue glucose metabolic rate Rg' and of the percentage of total glucose uptake incorporated into specific storage products (Cf) are derived from tissue analysis after bolus administration of 2-[3H]deoxyglucose and [14C]glucose during the plateau phase of the euglycemic clamp. The effects of insulin elevation have been examined in several tissues. Rg' in diaphragm increased 10-fold over basal (maximal) with a half-maximal sensitivity (ED50) of 150 mU/l. This was similar to the ED50 for net whole body glucose utilization of 133 mU/l. In adipose tissue Rg' increased by twofold and Cf into lipids by sixfold; both were near maximal at 150 mU/l (ED50 of 60 mU/l). A small but significant insulin effect (Rg' increased 2-fold) was found in lung. Insulin did not significantly increase Cf into total liver lipids or glycogen. The methodology described here significantly increases the usefulness of the glucose clamp technique in the study of insulin action. Dose-response curves for insulin action during the euglycemic clamp vary considerably among different target tissues in the rat.
Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion
Authors: Wolfe R. R. , Shaw J. H. , Durkot M. J.
Published: December 2017

The effect of gram-negative sepsis on the kinetics and oxidation of very low-density lipoprotein (VLDL) fatty acids was assessed in conscious dogs in the normal state and 24 h after infusion of live Escherichia coli. VLDL, labeled with [2-3H]glycerol and [1-14C]palmitic acid, was used to trace VLDL kinetics and oxidation, and [1-13C]palmitic acid bound to albumin was infused simultaneously to quantify kinetics and oxidation of free fatty acid (FFA) in plasma. Sepsis caused a fivefold increase in the rate of VLDL production (RaVLDL). In the control dogs, the direct oxidation of VLDL-fatty acids was not an important contributor to their overall energy metabolism, but in dogs with sepsis, 17% of the total rate of CO2 production could be accounted for by VLDL-fatty acid oxidation. When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis. We conclude that the increase in triglyceride concentration in fasting dogs with gram-negative sepsis is the result of an increase in VLDL production and that the fatty acids in VLDL can serve as an important source of energy in sepsis.
Effects of [15N]leucine infused at low rates on leucine metabolism in humans
Authors: Tessari P. , Tsalikian E. , Schwenk W. F. , Nissen S. L. , Haymond M. W.
Published: December 2017

The present studies were carried out to determine whether infusions of [15N]leucine at low rates affect estimates of leucine oxidation and of proteolysis and protein synthesis in humans. Three groups of normal subjects were infused for 3 h with either [15N]leucine at a rate of 0.16 or 0.26 mumol X kg-1 X min-1 or saline using [2H3]leucine and alpha-[14C]ketoisocaproate as isotopic tracers of leucine metabolism. Data were analyzed at steady state using both single- and dual-isotope models. Preliminary studies were carried out to characterize the dual-isotope model in humans using infusions of [3H]leucine and alpha-[14C]ketoisocaproate. In the postabsorptive state estimates of leucine appearance, disappearance, and oxidation derived from the two isotope models were in good agreement. Infusion of stable isotope up to approximately 10% of the leucine carbon flux do not have a significant effect on leucine metabolism, but the data derived from such studies must be properly controlled and interpreted with care because these tracers are not massless.
Relation between blood flow and morphology in islet organ of rat pancreas
Authors: Lifson N. , Lassa C. V. , Dixit P. K.
Published: December 2017

By intra-arterial postmortem staining of the pancreas with hematoxylin after the administration of nonradioactive microspheres to anesthetized unfasted rats, the following values (+/-SE) were obtained: mean single islet volume, 1.00 +/- 0.12 nl (median 0.32 +/- 0.04 nl, n = 14); pancreatic intensity of perfusion, 1.18 +/- 0.14 ml X min-1 X g-1 (n = 10); percentage of pancreatic flow to islets, 6 +/- 1% (n = 10); single islet blood flow, 20 +/- 3 ml X min-1 (n = 10); and islet perfusion, 19 +/- 3 ml X min-1 X g-1 (n = 10). Perfusion of islet tissue was calculated to be above average for very small islets and to decrease with increasing islet size to become below average for very large ones. Details of the distribution of the total islet flow to subpopulations of islets grouped according to single islet size are shown pictorially.
Copper transport in rats involving a new plasma protein
Authors: Weiss K. C. , Linder M. C.
Published: December 2017

The time course of distribution of high-specific activity 67CuCl2 to tissues and plasma components was followed in adult, female rats. Immediately after intubation or injection, tracer 67Cu associated with two components of the blood plasma separable on columns of Sephadex G-150: albumin and another (larger) component, which was not ceruloplasmin. The latter, tentatively named transcuprein, had an apparent molecular weight of 270,000 and a high affinity for Cu2+, as judged by processing through Chelex-100, dilution, and exchange with albumin copper, in vitro and in vivo. It was capable of donating copper to tumor cells in serum-free medium. Analysis of "cold" plasma by furnace atomic absorption confirmed the presence of 10-15% of plasma copper in this peak. Plots of percent dose and 67Cu specific activity against time showed that copper followed a very specific pathway after binding to albumin and transcuprein, entering mainly the liver, then reappearing in the plasma on ceruloplasmin, and then achieving peak distribution in peripheral tissues (muscles, brain, etc.). 67Cu disappeared from liver and kidney with an apparent half-life of 4.5 days, the same exponential rate found for whole body turnover. Apparent turnover of ceruloplasmin copper was more rapid. Even after 7-12 days, tracer copper in plasma was still found exclusively with ceruloplasmin. The results indicate that copper follows a carefully prescribed path, on entering the blood and binding to a new transport protein.
Leucine turnover and oxidation in trained rats during exercise
Authors: Henderson S. A. , Black A. L. , Brooks G. A.
Published: December 2017

The effects of training on leucine turnover and oxidation were studied during rest and exercise in young, postabsorptive female rats. Relationships were primarily studied by the continuous infusion method, using [1-14C]leucine. Arterial blood was assayed for leucine specific activity and expired air was monitored for O2 consumption, CO2 production, and the specific activity of 14CO2. The rate of leucine turnover in trained rats was 70% greater than the rate of leucine turnover in untrained rats and was not affected by exercise. By virtue of a higher turnover, the rate of leucine oxidation was 40% greater in trained rats during both rest and exercise. Moreover, leucine oxidation was proportional to the metabolic rate and represented 30% of the leucine turnover at rest and 40-60% of the leucine turnover during exercise. In the same animals leucine turnover was secondarily assessed by measuring the fraction of the [1-14C]leucine dose contained in the hemoglobin pool 4 wk after infusion (occupancy tracer method). Occupancy values for leucine turnover were not different from those determined by the continuous infusion method. The results show that whole body leucine turnover is increased by training and that leucine oxidation is increased by both training and exercise.
Involvement of arachidonate metabolism in neurotensin-induced prolactin release in vitro
Authors: Canonico P. L. , Speciale C. , Sortino M. A. , Scapagnini U.
Published: December 2017

Neurotensin increased in a concentration-dependent manner the level of hypophyseal [3H]arachidonic acid in vitro as well as prolactin release from hemipituitary glands. The effect of 1 microM neurotensin on arachidonate release was already present at 2.5 min, maximal at 5, and disappeared after a 10-min incubation. Neurotensin analogues produced an enhancement of hypophyseal arachidonate similar to their relative potencies in other cellular systems, whereas other peptides (somatostatin and vasoactive intestinal peptide) were devoid of any effect on the concentration of the fatty acid in the pituitary. Seventy micromoles RHC 80267, a rather selective inhibitor of diacylglycerol lipase, completely prevented the neurotensin-stimulated prolactin release and decreased arachidonate release both in basal or in neurotensin-induced conditions. Similar results were obtained with 50 microM quinacrine, a phospholipase A2 inhibitor. To clarify whether arachidonate released by neurotensin requires a further metabolism through specific pathways to stimulate prolactin release, we used indomethacin and BW 755c, two blockers of cyclooxygenase and lipoxygenase pathways. Thirty micromoles indomethacin, a dose active to inhibit cyclooxygenase, did not affect unesterified arachidonate levels either in basal or in neurotensin-induced conditions; moreover, the drug did not modify basal prolactin release but slightly potentiated the stimulatory effect of neurotensin on the release of the hormone. On the other hand, 250 microM BW 755c, an inhibitor of both cyclooxygenase and lipoxygenase pathways, significantly inhibited both basal and neurotensin-stimulated prolactin release and further potentiated the increase of the fatty acid concentrations produced by 1 microM neurotensin.(ABSTRACT TRUNCATED AT 250 WORDS)