bluuebunny/crossref_metadata_2025 huggingface dataset:
Nycterohemeral difference in inhibition of stress-induced ACTH in adrenalectomized rats
Authors: Wilson M. M. , Greer S. E. , Greer M. A.
Published: December 2017

To determine the interactions among the determinants of ACTH secretion, we examined the influence of circadian rhythmicity on glucocorticoid suppression of ACTH. Adrenalectomized rats were injected with the same amount of corticosterone at 0900 and 1800 h, and plasma ACTH concentrations were determined under basal conditions and after a standard ether stress. At 0900 h, corticosterone suppressed both basal and stress-induced plasma ACTH concentrations. At 1800 h, the same treatment suppressed basal ACTH secretion but not the stress-induced rise. Although the same amount of corticosterone was injected at both times of day, the plasma corticosterone concentration 5 min after injection was higher at 1800 h than at 0900 h. This study indicates that there is a nycterohemeral difference in feedback suppression of stress-induced ACTH secretion by a given dose of corticosterone. The daily variation in feedback inhibition may be due to the additive effect of the evening surge stimulus and the stress stimulus that together override the feedback signal.
Interactions of Ca2+, Mg2+, and Na+ in regulation of insulin release from rat islets
Authors: Janjic D. , Wollheim C. B.
Published: December 2017

The effects of glucose and ionic modifications on unidirectional Ca2+ efflux and insulin release has been studied. Rat pancreatic islets were isotopically equilibrated with 45Ca2+ for 2 days and then perifused at 10(-8) M Ca2+ to allow for strict interpretation of 45Ca2+ efflux. Under these conditions 16.7 mM glucose inhibited Ca2+ efflux but did not stimulate insulin release. Removal of Mg2+ from the buffer markedly stimulated Ca2+ efflux that was counteracted by glucose. The omission of Na+ decreased basal Ca2+ efflux by 30% at 10(-8) M Ca2+, thus demonstrating the importance of Na-Ca countertransport for Ca2+ extrusion. Like glucose, Na+ omission or the addition of ouabain attenuated Ca2+ efflux stimulated by Mg2+ removal. Glucose may interfere with Na-Ca countertransport because the actions of 16.7 mM glucose and Na+ omission were not additive. At 10(-8) M Ca2+, glucose elicited insulin release only when both 1) loss of cellular calcium was minimized by prior inhibition of Ca2+ efflux (Na+ omission or ouabain), and 2) Ca2+ mobilization was favored by Mg2+ removal. Under these conditions (in contrast to normal Ca2+), insulin release was not accompanied by increased Ca2+ efflux. Thus, unidirectional Ca2+ measurements do not permit the detection of Ca2+ mobilization in intact islets because glucose may concomitantly inhibit Ca2+ extrusion.
Epinephrine modifications of insulin release and of 86Rb+ or 45Ca2+ fluxes in rat islets
Authors: Tamagawa T. , Henquin J. C.
Published: December 2017

The effects of epinephrine on insulin release, 86Rb+ fluxes, and 45Ca2+ fluxes were measured in rat islets. In the presence of 10 mM glucose, epinephrine did not affect 86Rb+ influx and slightly increased net uptake. It caused a monophasic inhibition of release and a biphasic decrease in 86Rb+ efflux. A maximum effect was observed with 1 microM epinephrine, but release was more markedly inhibited by lower concentrations of the catecholamine than was the efflux. Epinephrine inhibition of release and efflux was reversed by phentolamine and yohimbine but not by prazosin or propranolol. It was mimicked by norepinephrine and clonidine. The inhibition of 86Rb+ efflux persisted when insulin release was prevented by omission of extracellular calcium. Ouabain or high K+ markedly increased 86Rb+ efflux in the presence of glucose and epinephrine; theophylline and quinine had a similar but smaller effect. None of these agents restored insulin release. Epinephrine abolished the insulinotropic effect of arginine without altering the rise in 86Rb+ efflux triggered by the amino acid. Epinephrine abolished insulin release but inhibited 45Ca2+ efflux only partially during stimulation by glucose or by barium plus theophylline. The results show that epinephrine does not inhibit insulin release by activating the Na pump or by increasing K permeability of the B cell membrane. On the contrary, the inhibition of release is accompanied by a decrease in 86Rb+ efflux. Both result from activation of alpha 2-receptors but are not causally related; they could be due to remodeling of Ca2+ fluxes and/or changes in cAMP levels.
Biological activity of a growth hormone-releasing factor secreted by a human tumor
Authors: Cronin M. J. , Rogol A. D. , MacLeod R. M. , Keefer D. A. , Login I. S. , Borges J. L. , Thorner M. O.
Published: December 2017

A substance released by a pancreatic islet cell tumor induced signs and symptoms of acromegaly in a young woman. The culture medium in which the tumor was placed after resection was added to rat anterior pituitary cells and incubated in vitro. Both newly synthesized and total rat growth hormone (GH) release as well as cellular cyclic AMP accumulation were stimulated in a dose-dependent manner by the tumor medium. Coincubation with somatostatin blocked these effects. The increase of cyclic AMP preceded the enhanced GH release, indicating that cyclic AMP may be a second messenger for the tumor factor(s). Neither prolactin nor luteinizing hormone secretion was affected by the tumor medium. When measured by a perfused cell column apparatus, there was a rapid and dramatic release of GH by the dispersed rat pituitary cells during a 2.5-, 10-, and 40-min pulse of tumor medium; both the onset and termination of the GH response reached maximal or control values, respectively, within 5 min. Pretreatment of the tumor medium with pepsin markedly attenuated the tumor medium activity, indicating the peptide nature of the factor(s). Finally, ultrastructural analysis indicated that the somatotrophs were degranulated by the tumor medium, whereas there was no similar effect apparent on the mammotrophs. Whether this tumor polypeptide is identical to native hypothalamic GH-releasing hormone remains to be proved.
Direct tonic inhibition of insulin secretion by central nervous system
Authors: Curry D. L.
Published: December 2017

An experimental animal model was developed to investigate the influence of the central nervous system (CNS) on insulin secretion via direct innervation to the pancreas. This model eliminates any indirect CNS effect on the pancreas by hormonal factors. It consists of a vascularly isolated, in situ perfused rat pancreas preparation with the cephalic portion of the animal functional, including innervation to the pancreas. Using this rat model, we have demonstrated that the nonstimulated rat brain exerts a tonic inhibition of glucose-stimulated insulin secretion in nonfasted rats. This inhibition can only occur directly via neurons from brain to pancreas, probably via the sympathetic nervous system. The brain does not alter the biphasic pattern of insulin secretion, but it suppresses the overall insulin secretory process throughout both phases of insulin secretion by a relatively constant degree ranging from 38 to 47%. The physiological purpose of this tonic suppression of insulin secretion is open to speculation, but it is well known that tonic sympathetic stimulation of the cardiovascular system represents an important physiological control mechanism. An analogous control may exist with respect to insulin secretion.
Erythropoietin in liver tissue extracts and in liver perfusates from hypoxic rats
Authors: Caro J. , Zon L. I. , Silver R. , Miller O. , Erslev A. J.
Published: December 2017

An attempt to evaluate the role of the liver in extrarenal erythropoietin production was made by measuring the content of erythropoietin in homogenates and perfusates from hypoxic rat livers. Extracts from livers from nephric or anephric animals rendered both anemic and hypoxic showed no detectable erythropoietin despite the fact that both plasma and kidney extracts contained large amounts of erythropoietin. This lack of measurable erythropoietin in the liver is not caused by degradation of erythropoietin during the extraction procedure because exogenously added rat erythropoietin was recovered to the same extent from livers or kidney homogenates. More likely, however, it is caused by the fact that extrarenal erythropoietin production accounts for only one-fifth of total erythropoietin production and that the liver mass is about six times that of both kidneys. Consequently, the erythropoietin content of 1 g of liver should be about one-thirtieth of that of 1 g of kidney, an amount that is below the limit of detection of the assay. On the other hand, the 2-h in situ perfusates of livers from similarly stimulated animals contained significant amounts of secreted erythropoietin. It is concluded that the liver participates actively in extrarenal erythropoietin production in the adult rat. However, the small amount expected to be present in tissue homogenates cannot be detected with our current bioassay.
Vasopressin, ACTH, and corticosteroids during hypercapnia and graded hypoxia in dogs
Authors: Raff H. , Shinsako J. , Keil L. C. , Dallman M. F.
Published: December 2017

We examined the interaction of graded hypoxia and hypercapnia on stimulation of vasopressin (AVP), ACTH, and corticosteroids in nonsurgically stressed, pentobarbital-anesthetized, gallamine-paralyzed ventilated dogs. Partial pressure of O2 in arterial blood (PaO2) levels of approximately 26-29, 38-41, 54-57, and 83-88 Torr were achieved by altering the fractional concentration of O2 in dry inspired gas with a normocapnic (PaCO2, 35 Torr) and hypercapnic (PaCO2, 59 Torr) background. Normocapnic hypoxia produced a PaO2-dependent increase in AVP, ACTH, and corticosteroids. The threshold PaO2 for AVP was lower (approximately 35 Torr) than for ACTH (approximately 45 Torr). AVP, ACTH, and corticosteroids at all PaO2 levels were higher during hypercapnia. In addition, an ACTH and corticosteroid dose-response correlation estimated the threshhold ACTH to be 20-30 pg/ml. The PaO2-dependent hormone increases and the augmentation of these relationships by hypercapnia are consistent with a peripheral chemoreceptor-mediated reflex. In addition, hypoxia and hypercapnia did not seem to alter the high sensitivity of the adrenal cortex for ACTH.
Dopamine stimulates somatostatin release from perifused hypothalamic cells
Authors: Richardson S. B. , Nguyen T. , Hollander C. S.
Published: December 2017

We studied the release of immunoreactive somatostatin (IR-SRIF) from hypothalamic cells that were obtained from rats and dispersed with the aid of collagenase. Twenty-four hours after dispersion, cells were placed in a column supported by a matrix of preswollen Biogel P2 and perifused. Fractions were collected on ice and subsequently assayed for SRIF. SRIF release was stimulated markedly by potassium depolarization (KCl, 56 mM), by the Na+-K+-ATPase inhibitor ouabain (10(-4) M), and by dopamine at concentrations as low as 10(-11) M. The stimulatory effects of membrane depolarization were calcium dependent and were not observed in the absence of exogenous calcium in the perifusion medium or in the presence of EDTA (0.05 M). Metoclopramide, the dopamine antagonist, abolished the stimulatory effect of dopamine. In conclusion, release of IR-SRIF by dispersed rat hypothalamic cells can be studied in a simple perifusion apparatus. Release is stimulated by membrane depolarization in a calcium-dependent manner and by dopamine at physiological concentrations.
Fatty acid and glucose utilization in isolated, working fetal pig hearts
Authors: Werner J. C. , Whitman V. , Fripp R. R. , Schuler H. G. , Musselman J. , Sham R. L.
Published: December 2017

Fatty acid uptake and the effects of long- and short-chain fatty acids on glucose utilization were assessed in isolated perfused fetal pig hearts (0.9 gestation) in which oxygenated nutrient buffer was pumped from both ventricles at controlled pressure (55 mmHg, mean arterial pressure) and heart rate (180 beats/min). When either 1.5 mM palmitate or 1.0 mM octanoate was added to buffer containing 10 mM glucose and insulin (100 microU/ml), glucose uptake, as measured by 3H2O production from D-[2-3H]glucose, was suppressed when compared with glucose uptake in the absence of fatty acid. Increased tissue concentrations of glucose 6-phosphate, fructose 6-phosphate, and citrate in hearts perfused with buffer containing octanoate indicated active beta-oxidation and inhibition of phosphofructokinase activity when compared with hearts perfused with glucose alone. In contrast, hearts perfused with buffer containing palmitate showed no increases in these metabolic intermediates. These results suggest that suppression of glucose uptake in the presence of long-chain fatty acid was not the result of phosphofructokinase inhibition but may result from inhibition of glucose transport by palmitate. Determinations of tissue concentrations of free carnitine and carnitine derivatives indicated that, although palmitate underwent esterification to long-chain acyl carnitine in the fetal heart, it failed to undergo extensive beta-oxidation.
Fatty acid synthesis in adipose tissues of physically trained rats in vivo
Authors: Tokuyama K. , Okuda H.
Published: December 2017

The effect of physical training on fatty acid synthesis in vivo was studied. After the rats had free access to a running wheel for 50 days, the rate of fatty acid synthesis estimated using 3H2O in adipose tissues of trained rats was about three times higher than that of sedentary rats in both the light and dark period. The rate of fatty acid synthesis in the liver but not in the brown adipose tissue was also slightly enhanced by physical training. The number of adipocytes was not affected, but the size of adipocytes was reduced by physical training. In trained rats, the rate of fatty acid synthesis in adipocytes whose diameter was similar to that of sedentary rats was about 10 times higher than that of sedentary rats. Within adipose tissue, the rate of fatty acid synthesis correlated positively to the diameter of adipocytes both in the sedentary and trained rats. These findings mean that the adaptive increase in fatty acid synthesis seen in adipocytes of trained rats is not secondary to the reduction in size of adipocytes.
Effects of gastric inhibitory polypeptide on leucine- and arginine-stimulated insulin release
Authors: Mazzaferri E. L. , Ciofalo L. , Waters L. A. , Starich G. H. , Groshong J. C. , DePalma L.
Published: December 2017

Insulin release stimulated by single amino acids, with and without gastric inhibitory polypeptide (GIP), was studied in vivo in anesthetized rats and in vitro in collagenase-digested isolated rat pancreatic islets. Insulin release in vivo during a 15-min intravenous infusion of leucine (0.97 mM) or arginine (0.97 mM) with GIP (17 ng/min) was greater than with infusion of either amino acid or GIP alone. Serum immunoreactive GIP was in the physiological range, and serum glucose showed no significant change in these studies. In contrast, insulin release did not occur with valine infused alone or with GIP. Insulin release in vitro by isolated islets was greater during a 45-min incubation period with leucine (5-20 mM) or arginine (20 mM) plus GIP (10 ng to 10 micrograms/ml) than with either amino acid alone. This effect that occurred in the absence of glucose could not be demonstrated with low concentrations of leucine (1.5 mM) or with 20 mM valine. In vitro insulin release during paired perfusion studies of isolated islets was greater with leucine (20 mM) plus GIP (50 ng/min) than with leucine alone, and augmentation of insulin release by GIP was demonstrable in both the early and late phases of insulin release. From these results it is concluded that insulin release is greater, both in vivo and in vitro, after leucine or arginine plus GIP than with either amino acid or GIP alone. This effect appears to be specific for the insulinotropic amino acids tested, does not appear to be glucose dependent, and can be demonstrated in both the early and late phases of insulin release.
Estimation of glucose carbon recycling and glucose turnover with [U-13C] glucose
Authors: Tserng K. Y. , Kalhan S. C.
Published: December 2017

To estimate "true" rate of glucose production, as well as glucose carbon recycling in humans, a mass spectrometric method with [U-13C]glucose as tracer was developed. Because the opportunity for the uniformly labeled glucose, [13C6]glucose, to recycle back as [13C6]glucose is negligible, the true glucose production rate was obtained by measuring the plasma isotope enrichment of [13C6]glucose with chemical ionization mass spectrometry. In contrast, when the isotopic enrichment of C-1 of glucose was measured by enzymatic decarboxylation and ratio mass spectrometry, the "apparent" glucose production including carbon recycling was obtained. The difference between the two rates was the extent of glucose carbon recycling. [U-13C]glucose was administered as primed constant-rate infusion to six normal healthy adult subjects. Rates of glucose turnover were calculated from tracer dilution by applying steady-state kinetics. The true rate of glucose production estimated by the present method was 2.02 +/- 0.19 mg X kg-1 X min-1 (mean +/- SD). After an overnight fast, glucose carbon recycling contributed from 3 to 26% of the total glucose production rate. Use of stable isotopes and mass spectrometric technique permits estimation of important parameters of glucose metabolism without resorting to multiple tracers and at the same time preventing the risk of radiation.
Control of brown adipose tissue lipolysis and respiration by adenosine
Authors: Szillat D. , Bukowiecki L. J.
Published: December 2017

Adenosine competitively inhibited the stimulatory effects of (-)-isoproterenol on lipolysis and respiration in hamster brown adipocytes. The low value of the apparent ki for respiratory inhibition by adenosine (7 nM) indicated that the nucleoside may control brown adipocyte function under physiological concentrations. Significantly, the dose-response curves for isoproterenol stimulation of lipolysis and respiration were both shifted by adenosine to higher agonist concentrations by the same order of magnitude, providing additional evidence for a tight coupling between lipolysis and respiration. The inhibitory effects of adenosine were rapidly reversed by a) adenosine deaminase, b) agents known to increase intracellular cyclic AMP levels (isoproterenol, isobutylmethylxanthine, dibutyryl cyclic AMP), and c) direct stimulation of respiration with palmitic acid. These results, combined with the fact that adenosine failed to affect respiration evoked either by dibutyryl cyclic AMP or by palmitic acid, strongly indicate that adenosine regulates brown adipose tissue respiration at an early metabolic step of the stimulus-thermogenesis sequence, most probably at the level of the adenylate cyclase complex.
Suppression of norepinephrine-induced thermogenesis in brown adipose tissue by fasting
Authors: Hayashi M. , Nagasaka T.
Published: December 2017

Fasting-induced changes in thermogenic responses to norepinephrine (NE, 4.0 micrograms X kg-1 X min-1 iv) were studied in anesthetized rats previously cold acclimated. The rats were divided into five groups at the end of 30–40 days of cold acclimation (5 degrees C). The five groups were kept for 5 days at 25 degrees C and fed (intact fed), fasted (intact fasted), fasted with daily treatment with thyroxine (T4, 2 micrograms/kg sc), thyroidectomized and fed, or thyroidectomized and fasted. In the intact fasted group, in which the weight of brown adipose tissue decreased, NE-induced increases in oxygen consumption, colonic temperature (T col), and temperature of the interscapular brown adipose tissue (TBAT) were markedly suppressed. The two thyroidectomized groups also showed a reduction in thermogenic response. In these three groups, TBAT was lower than Tcol throughout NE infusion. In the T4-treated fasted group, fasting-induced suppression of thermogenic response to NE was largely prevented. In the intact fed and the T4-treated fasted groups, TBAT attained higher values than Tcol during NE infusion. Plasma levels of thyroid hormones were significantly lower in the intact fasted group than in the intact fed or the T4-treated fasted group. These results suggest that fasting-induced suppression of the thermogenic response to NE is largely due to the reduced thermogenic response of brown adipose tissue to NE. The lowering of the levels of the thyroid hormones induced by fasting may be one of a number of causes of the reduction in the thermogenic response of brown adipose tissue.
A role for endogenous prostaglandin E in biphasic pattern of insulin release in humans
Authors: Giugliano D. , Di Pinto P. , Torella R. , Frascolla N. , Saccomanno F. , Passariello N. , D'Onofrio F.
Published: December 2017

These studies were undertaken to evaluate in humans the possible physiological role of prostaglandins of the E series (PGE) in modulating insulin release and to assess whether endogenous PGE synthesis may account for the biphasic pattern of insulin secretion. We used a square-wave glucose stimulation previously determined to give maximal biphasic insulin release. Infusion of lysine acetylsalicylate to block the synthesis of endogenous PGE increased by twofold total insulin response to glucose and also converted insulin release to a multiphasic pattern. The infusion of exogenous PGE1 (0.2 microgram X kg-1 X min-1) or PGE2 (10 micrograms/min) in addition to lysine acetylsalicylate restored the typical biphasic pattern of insulin release and also decreased total insulin release to values similar to those of control studies. Infusion of either PGE1 or PGE2 in the absence of lysine acetylsalicylate reset insulin secretion to a lower level without altering the kinetics of release. On the basis of these results, it is hypothesized that endogenous PGE released in response to glucose stimulation exert an inhibiting effect on insulin release that becomes biphasic in appearance.
Splanchnic clearance of plasma vasopressin in the dog: evidence for prehepatic extraction
Authors: Matsui K. , Share L. , Brooks D. P. , Crofton J. T. , Rockhold R. W.
Published: December 2017

It is generally considered that the liver is primarily responsible for the extraction of vasopressin from the circulating blood by the splanchnic viscera. To investigate this matter further, measurements were made in the anesthetized dog of the concentrations of vasopressin in arterial, portal venous, and hepatic venous plasma, and of total splanchnic plasma flow and hepatic arterial plasma flow. The total splanchnic vasopressin extraction ratio was 12.9 +/- 1.0%. However, the concentration of vasopressin in portal venous plasma was consistently lower than in arterial plasma, and there was a substantial prehepatic extraction of vasopressin, averaging 10.5 +/- 0.8%. A quantitative evaluation of the contribution of the “prehepatic” viscera, i.e., viscera with venous drainage into the portal vein, is provided by the relevant clearances of vasopressin. The prehepatic and total splanchnic vasopressin clearances were 1.58 +/- 0.20 and 3.04 +/- 0.31 ml X min-1 X kg-1, respectively. Thus, the splanchnic viscera other than the liver were responsible for approximately half of the splanchnic clearance of vasopressin; the remainder could be attributed to the liver. Immunoreactive vasopressin was not found in the bile. In splenectomized dogs, in which venous blood was collected from the superior mesenteric vein, the vasopressin extraction ratio was 14.6 +/- 2.3%, suggesting that the prehepatic clearance of vasopressin occurs largely in the mesenteric bed. A more specific localization of the prehepatic clearance sites has not as yet been made.
Mechanism of renin release in exercising dog
Authors: Zambraski E. J. , Tucker M. S. , Lakas C. S. , Grassl S. M. , Scanes C. G.
Published: December 2017

Exercise is associated with an increase in plasma renin activity (PRA). The purpose of this study was to determine the role of the prostaglandin (PG) and adrenergic pathways in the renin release with exercise in the dog. One group of animals (n = 4) was exercised under control untreated and indomethacin- and meclofenamate- (2 mg/kg) treated conditions. A 155% increase in PRA was not influenced by PG inhibition. In a second group (n = 7) PRA was 1.22 +/- 0.32, 3.29 +/- 1.59, 6.28 +/- 2.85, and 5.30 +/- 2.00 ng ANG I X ml-1 X h-1 at rest and during light, moderate, and heavy exercise, respectively. Guanethidine treatment (15 mg/kg) decreased mean PRA by 41, 50, 70, and 73% at rest and during the three levels of exercise, respectively. In a third group (n = 5) control exercise runs were repeated after metoprolol treatment. Selective beta 1-blockade completely abolished the increment in PRA observed with exercise. These data demonstrate that the elevation of PRA during exercise in the dog is mediated by increased sympathetic nerve activity involving beta 1-receptors and that it is not dependent on alterations in PG synthesis.
Phosphorylase activation hypersensitivity in hearts of diabetic rats
Authors: Miller T. B.
Published: December 2017

A hypersensitivity of glycogen phosphorylase activation by epinephrine and glucagon has been demonstrated in isolated perfused working and non-working hearts from diabetic rats. Accumulation of tissue cAMP and activation of cAMP-dependent protein kinase in response to epinephrine and glucagon were no greater and usually less in hearts of diabetic than of normal rats. Insulin deficiency was not associated with greater changes in epinephrine-induced activation of glycogen phosphorylase kinase than that observed in normal hearts. Perfusion of hearts with subphysiological concentrations of calcium (0.83 mM) partially reversed the diabetes-related hypersensitivity of phosphorylase activation by epinephrine. The phosphorylase activation hypersensitivity to epinephrine was completely reversed by adrenalectomizing diabetic rats 5 days before heart perfusion, an effect potentially caused by steroid-induced changes in cardiac calcium metabolism. These data are consistent with the hypothesis that phosphorylase activation by phosphorylase kinase is allosterically increased in the diabetic due to a diabetes-related increase in free intracellular calcium concentrations.
Bidirectional alteration of insulin receptor affinity by different forms of physical exercise
Authors: Michel G. , Vocke T. , Fiehn W. , Weicker H. , Schwarz W. , Bieger W. P.
Published: December 2017

Insulin binding of monocytes and erythrocytes was studied in untrained male volunteers after 15 min of exhaustive bicycle exercise (EE) and several days later after moderate exercise (ME) for 90 min. Insulin receptor affinity decreased after EE in monocytes (26.4% decrease; P less than 0.01) and in erythrocytes (10.4%; P less than 0.05) with no change in receptor number. After ME, however, binding to monocytes was enhanced by 15.2% (P less than 0.05) due to increased receptor affinity. The number of circulating monocytes was markedly increased after both forms of exercise, averaging 105% after EE and 57% after ME. The bidirectional effect on monocyte insulin binding could be reproduced in vitro by incubation of preexercise cells with post-exercise serum: 12.4% (P less than 0.05) decrease with EE serum and 6.1% (P less than 0.05) increase with ME serum. The effect was prevented by overnight dialysis. These results suggest that physical exercise not only entails adjustment of serum insulin but also of cellular hormone sensitivity, presumably through the mediation of low-molecular-weight serum components.
Chronic norepinephrine infusion and insulin and glucagon secretion in the dog
Authors: Raum W. J. , Swerdloff R. S. , Garner D. , Laks H. , Laks M. M.
Published: December 2017

The effect of epinephrine on glucose homeostasis has been studied extensively in many species, but there is little data on the effects of another catecholamine, norepinephrine. This study was designed to examine the alterations that occur in insulin and glucagon secretion during a chronic low-dose infusion of norepinephrine in free-roaming dogs. A total of four intravenous glucose tolerance tests and insulin-induced hypoglycemia tests were performed on each of five dogs infused with norepinephrine (1.4 g/min) for 3 mo and on each of eight control dogs. The infusion resulted in a threefold increase in plasma norepinephrine without a significant effect on blood pressure. Fasting serum glucose was elevated significantly in the norepinephrine-infused dogs [102.4 +/- 2.1 vs. 92.8 +/- 1.7 (SE) mg/100 ml]. Fasting plasma glucagon was elevated by the norepinephrine infusion (58.4 +/- 7.6 vs. 31.3 +/- 3.1 pg/ml), whereas fasting serum insulin was inhibited (12.3 +/- 1.3 vs 16.8 +/- 1.7 U/ml). Glucagon secretion in response to hypoglycemia was markedly enhanced in the infused dogs compared with controls. It has been reported that the infusion of norepinephrine in humans will inhibit insulin secretion and increase serum glucose concentrations but have no effect on serum glucagon concentrations. The stimulation of glucagon by norepinephrine has been demonstrated in the isolated, perfused canine pancreas but has not been reported previously in the free-roaming dog.
Effects of diet and obesity on brown adipose metabolism
Authors: Levin B. E. , Finnegan M. B. , Marquet E. , Triscari J. , Comai K. , Sullivan A. C.
Published: December 2017

The effect of diet-induced obesity on interscapular brown adipose tissue (IBAT) was assessed after feeding male Sprague-Dawley rats a high-fat diet for 3-5 mo beginning at 3 mo of age. IBAT pads in 6-mo-old obese rats were heavier (22%), had more lipid (71%), and larger unilocular cells (38%) than chow-fed controls. Mitochondrial morphology, beta-adrenergic receptor binding ([ 125I]iodocyanopindolol), and norepinephrine-stimulated lipolysis were similar in IBAT from obese and control rats. When 8-mo-old chow-fed rats were switched to the high-fat diet for 7-14 days, IBAT pads became hypercellular without cell hypertrophy and with a 70% increase in norepinephrine-induced lipolysis. However, when 8-mo-old obese rats that had been on the high-fat diet for 5 mo were switched to chow for 3 days, IBAT cellularity was unchanged, but norepinephrine-induced lipolysis was increased 70%. Therefore, in lean and obese 6- to 8-mo-old rats, short-term dietary manipulation led to metabolic activation, whereas chronic diet-induced obesity on a stable diet was associated with a return of IBAT metabolism to control levels.
Glucoregulatory and metabolic responses to heat exposure in rats
Authors: Chayoth R. , Nakhooda A. F. , Poussier P. , Marliss E. B.
Published: December 2017

To determine the possible role of altered secretion and effects of insulin in fuel homeostasis during heat exposure, the hormonal and metabolic milieu of three groups of rats were studied. The first was placed at 35 degrees C for 12 days (HE), the second was pair-fed (PF) to the first but maintained at 23 degrees C, and the third was allowed to eat ad libitum at 23 degrees C (C). Plasma insulin, glucagon, glucose, and free fatty acids (FFA), and blood lactate, pyruvate, 3-hydroxybutyrate, and individual amino acids were determined. To further characterize glucoregulation, an intraperitoneal glucose tolerance test (1 mg/g body wt) and isotopic glucose turnover (primed infusion of [3-3H]glucose) were performed. In HE rats, weight was constant for the last third of the period, and metabolic state 4 h after food removal was characterized by euglycemia but hypoinsulinemia, elevated blood pyruvate and FFA, and normal 3-hydroxybutyrate compared with C. Lowered levels of branched-chain amino acids and arginine were found. Fourteen hours after food removal glucose turnover was decreased. However, glucose intolerance accompanied by hyperinsulinemia was also found. Many of these changes were also seen in PF, including constant weight, fasting euglycemia, hypoinsulinemia, elevated FFA, and lowered valine and isoleucine. In contrast, pyruvate concentrations were normal, that of 3-hydroxybutyrate was elevated, and the decrement in glucose turnover was smaller than in HE rats. The glucose tolerance was similar to that of HE but accompanied by hypoinsulinemia. The results in HE suggest decreased energy metabolism, insulin secretion altered in a complex manner, and altered insulin action.(ABSTRACT TRUNCATED AT 250 WORDS)
Difference in glucose dependency of insulin and somatostatin release
Authors: Ronner P. , Scarpa A.
Published: December 2017

The splenic Brockmann body of channel catfish (Ictalurus punctatus) was isolated and perfused in vitro. It has been shown previously that the hormone release from the catfish pancreas in response to various stimuli resembled that of a mammalian pancreas. The release of insulin and somatostatin was measured at various concentrations of glucose in the perfusate, and the corresponding dose-response curves were derived. As in a variety of mammalian pancreases, insulin release was stimulated half-maximally at ca. 9 mM glucose. In contrast, half-maximal somatostatin release occurred already at ca. 5 mM glucose. Although a comparable finding with mammalian D cells has not yet been reported, histological and physiological resemblances of the mammalian and the fish pancreas suggest that mammalian D cells may also have a glucose sensitivity in the 5 mM range.
Defective brown adipose oxygen consumption in obese Zucker rats
Authors: Levin B. E. , Finnegan M. B. , Marquet E. , Sullivan A. C.
Published: December 2017

The thermogenic capacity and morphologic characteristics of interscapular brown adipose tissue (IBAT) were assessed in 3- to 4-mo-old male, lean and obese Zucker rats. Pads from obese rats were threefold heavier and contained similar numbers of cells but an average of 50% fewer multilocular cells than pads from lean rats and 40% less mitochondrial protein per pad. The maximal number of beta-adrenoreceptor binding sites, as assessed by [125I]iodocyanopindolol binding to isolated brown adipocytes from obese rats was 50% of that in lean rats on a per cell and per pad basis. Basal and norepinephrine (NE)-stimulated in vitro oxygen consumption in isolated brown adipocytes from lean rats correlated directly with the proportion of mutilocular cells present. This correlation was not seen in cells from obese rats that had a 50% decrease in their basal respiratory rates and could not be further stimulated by excess NE or fatty acid. Electron micrographs of IBAT from obese rats revealed distorted mitochondrial shapes and cristae patterns and the presence of numerous inclusion bodies. Because NE-stimulated lipolysis had previously been shown to be normal in the obese Zucker rat, these data suggest that defective BAT thermogenesis in the obese rat is due to an inability of mitochondria to utilize free fatty acids for the production of enhanced oxygen consumption.
Effect of epinephrine on glycogenolysis and gluconeogenesis in conscious overnight-fasted dogs
Authors: Cherrington A. D. , Fuchs H. , Stevenson R. W. , Williams P. E. , Alberti K. G. , Steiner K. E.
Published: December 2017

The aim of this study was to assess the importance of epinephrine as a gluconeogenic hormone in the conscious 18-h-fasted dog. Glucose production ([3H]glucose turnover) and gluconeogenesis [( 14C]alanine conversion to [14C]glucose; and transhepatic gluconeogenic substrate balances) were assessed during epinephrine infusion (0.04 microgram X kg-1 X min-1). Insulin and glucagon were fixed at basal levels (13 +/- 1 microU/ml and 138 +/- 16 pg/ml, respectively) using a pancreatic clamp [somatostatin (0.8 microgram X kg-1 X min-1) plus intraportal insulin (233 microU X kg-1 X min-1) and glucagon (0.65 ng X kg-1 X min-1)]. Plasma epinephrine levels increased to 424 +/- 48 pg/ml. Glucose production increased rapidly (15 min) from 2.7 +/- 0.3 to 3.7 +/- 0.4 mg X kg-1 X min-1 (P less than 0.01) but then returned to base line (2 h). The plasma glucose level rose progressively from 115 +/- 16 to 160 +/- 16 mg/dl (P less than 0.01) at 3 h, whereas glucose clearance fell by 28% (P less than 0.05). Plasma alanine rose from 340 +/- 20 to 497 +/- 50 microM, and blood lactate increased from 640 +/- 135 to 1,910 +/- 241 microM. Net hepatic alanine and lactate uptake increased to maxima of 4.0 +/- 0.3 and 9.3 +/- 2.0 mumol X kg-1 X min-1, respectively. The conversion of alanine to glucose increased by a maximum of 163 +/- 56% (vs. 49 +/- 16% in controls not given epinephrine), whereas the efficiency with which the liver converted alanine to glucose rose by 84 +/- 27% (vs. 82 +/- 12% in controls not given epinephrine).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of epinephrine infusion on leucine and alanine kinetics in humans
Authors: Miles J. M. , Nissen S. L. , Gerich J. E. , Haymond M. W.
Published: December 2017

Infusion of epinephrine in humans increases glucose production and decreases plasma concentrations of some essential amino acids such as leucine, while not affecting the plasma concentration of the potential gluconeogenic amino acid alanine. To determine whether epinephrine alters alanine and leucine metabolism, rates of appearance (Ra) and disappearance (Rd) of glucose, alanine, and leucine were determined in postabsorptive volunteers using [3H]glucose, [2H3]alanine, [15N]leucine, and [2H3]leucine during a 180-min infusion of epinephrine (50 ng X kg-1 X min-1). Plasma glucose (90 +/- 1 to 142 +/- 5 mg/dl) and insulin (10 +/- 1 to 16 +/- 2 micrograms/ml) increased (P less than 0.05), whereas plasma alanine concentrations did not change and plasma leucine concentrations increased (127 +/- 5 to 72 +/- 3 microM). Glucose Ra increased transiently and returned to basal values by 120 min. In contrast, alanine Ra and Rd increased identically and progressively from 5.7 +/- 0.5 to 14.5 +/- 1.9 mumol X kg-1 X min-1 by 180 min. Although leucine nitrogen Ra increased transiently and returned to basal values, leucine carbon Ra and Rd decreased (P less than 0.05) during the infusion of epinephrine. The calculated rate and percent of leucine nitrogen going to alanine increased, whereas the percent of alanine nitrogen derived from leucine remained constant. The increase in alanine Ra was entirely attributable to increased de novo synthesis because proteolysis, as estimated by leucine carbon flux, decreased.
Synthase activation is not a prerequisite for glycogen synthesis in the starved liver
Authors: Van de Werve G. , Jeanrenaud B.
Published: December 2017

To evaluate the contribution of phosphorylase and synthase interconversion as well as the availability of substrates to the onset of liver glycogen synthesis, this process was studied in rats starved overnight and refed for 4 h. On feeding, phosphorylase kinase and phosphorylase were inactivated in a cAMP-independent way, but the proportion of synthase a was unchanged and associated with increased hexoses 6-phosphate (glucose and fructose 6-phosphate), uridine diphosphoglucose (UDPG), and fructose 2,6-bisphosphate concentrations. These findings serve to support a "push" mechanism whereby substrate availability for synthase a concerted with phosphorylase inactivation provokes glycogen deposition. Anesthesia was compulsory for liver sampling and analysis. If such experiments were carried out in conscious rats killed by decapitation, artefactual cAMP-dependent phosphorylase activation and synthase inactivation were observed in starved animals. The phosphorylase activation persisted in refed animals but by a cAMP-independent mechanism.
Role of calcium ions in insulin action on hexose transport in L6 muscle cells
Authors: Klip A. , Li G. , Logan W. J.
Published: December 2017

It has been proposed that Ca2+ ions mediate the stimulation by insulin of glucose uptake in muscle (Clausen, T., Cell Calcium 1:311–325, 1980). However, absolute measurements of the concentration of cytosolic free Ca2+, [Ca2+]i, during the course of insulin action have not been made. The stimulation of hexose uptake by insulin was studied in an in vitro model system of muscle cells, the L6 cell line. The following evidence suggests that Ca2+ ions are not likely to fulfill the purported role. 1) Insulin in Ca2+-free media induced stimulation of 2-deoxy-D-glucose uptake. 2) Elevation of [Ca2+]i with the ionophore A23187 did not enhance hexose uptake. 3) Insulin action was not diminished when the hormone was added to Ca2+-depleted cells in Ca2+-free media with A23187. 4) Hexose uptake was not affected by a number of agents thought to modify [Ca2+]i including epinephrine, caffeine, 2,4-dinitrophenol, hyperosmolar mannitol, salicylate, vanadate, veratrine, and trypsin. 5) Direct determinations of [Ca2+]i by fluorescence of the novel indicator Quin-2 did not show differences between basal and insulin-stimulated cells; under identical conditions hexose uptake was stimulated by the hormone. 6) Chelation of [Ca2+]i with Quin-2 in Ca2+-free media did not affect the response to insulin. 7) Low concentrations of trypsin (7.5 micrograms/ml) elevated [Ca2+]i but did not increase the rate of hexose uptake.
Three-dimensional reconstruction of metabolic data from quantitative autoradiography of rat brain
Authors: Hibbard L. S. , Hawkins R. A.
Published: December 2017

Quantitative autoradiography is a powerful method for studying brain function by the determination of blood flow, glucose utilization, or transport of essential nutrients. Autoradiographic images contain vast amounts of potentially useful information, but conventional analyses can practically sample the data at only a small number of points arbitrarily chosen by the experimenter to represent discrete brain structures. To use image data more fully, computer methods for its acquisition, storage, quantitative analysis, and display are required. We have developed a system of computer programs that performs these tasks and has the following features: 1) editing and analysis of single images using interactive graphics, 2) an automatic image alignment algorithm that places images in register with one another using only the mathematical properties of the images themselves, 3) the calculation of mean images from equivalent images in different experimental serial image sets, 4) the calculation of difference images (e.g., experiment-minus-control) with the option to display only differences estimated to be statistically significant, and 5) the display of serial image metabolic maps reconstructed in three dimensions using a high-speed computer graphics system.
Glucose production and utilization in children with glycogen storage disease type I
Authors: Tsalikian E. , Simmons P. , Gerich J. E. , Howard C. , Haymond M. W.
Published: December 2017

Glucose turnover rates were estimated with [2H2]glucose in five children with glycogen storage disease type I (GSD I) during sequential withdrawal of an infusion of glucose to determine whether their hypoglycemia was the result of decreased glucose production or increased rates of glucose utilization. Plasma glucose concentrations were 78 +/- 5 mg/dl during infusion of glucose at 6 mg X kg-1 X min-1 and decreased to 53 +/- 3 and 45 +/- 7 mg/dl during the 3 and 1.5 mg X kg-1 X min-1 glucose infusions, respectively. Total glucose flux during the 6 mg X kg-1 X min-1 glucose infusion was 7.3 +/- 0.7 mg X kg-1 X min-1 and decreased with reduction in the rate of glucose infused. Endogenous glucose production increased with each decrease in the rate of exogenous glucose infused. Following discontinuation of glucose infusion, endogenous glucose production was 3.9 +/- 0.3 mg X kg-1 X min-1, a value that was lower (P less than 0.05) than that observed in overnight-fasted normal children (6.3 +/- 0.3 mg X kg-1 X min-1) but not statistically different from the Ra of normal children fasted for 30 h (4.1 +/- 0.5 mg X kg-1 X min-1). Thus, children with GSD have glucose production rates that are 40% lower than those of normal children fasted overnight but equal to those of normal children fasted 30 h. Rates of glucose utilization during the 6 mg X kg-1 X min-1 glucose infusion were higher (0.05 less than P less than 0.1) than those of overnight-fasted normal children, despite lower plasma glucose concentrations when expressed on a body weight basis but not when expressed on the basis of estimated brain weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Nerve Na+-K+-ATPase, conduction, and myo-inositol in the insulin-deficient BB rat
Authors: Greene D. A. , Yagihashi S. , Lattimer S. A. , Sima A. A.
Published: December 2017

Nerve conduction slowing in acute diabetes in animals has been associated with both a diminished axolemmal transmembrane Na+ potential and a myo-inositol-related defect in nerve Na+-K+-ATPase activity. The interaction between these two potentially related defects, their reversibility, and their possible role in the nerve conduction slowing and axonopathy of diabetes are not well defined. Therefore, the effects of rigorous insulin replacement on peripheral nerve conduction velocity, myoinositol content, and Na+-K+-ATPase activity were studied in the spontaneously diabetic BB-Wistar rat, an animal model that manifests both conduction slowing and a characteristic progressive axonopathy. Twelve weeks of sustained hyperglycemia reduced both motor conduction velocity and Na+-K+-ATPase activity in sciatic nerve. Six weeks of subsequent vigorous insulin replacement normalized the enzymatic defect but only partially corrected diminished nerve conduction velocity. Hence, nerve conduction slowing in diabetic animals may be partly attributable to reduced nerve Na+-K+-ATPase activity, but a less readily reversible component of conduction slowing probably reflects structural alterations that occur in nerve within the first 3 mo of diabetes.
An experimental model of syndrome of inappropriate antidiuretic hormone secretion in the rat
Authors: Verbalis J. G.
Published: December 2017

An experimental model of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was developed using continuous subcutaneous infusions of arginine vasopressin (AVP) or 1-desamino-8-D-arginine vasopressin (DDAVP) in conscious unrestrained rats drinking 5% dextrose solution. Retention of both ingested water and endogenously generated free water from tissue catabolism was the primary determinant of hyponatremia using either AVP or DDAVP infusions. Natriuresis occurred transiently following water expansion but only slightly further lowered plasma [Na+]. Cessation of antidiuretic infusion resulted in free water excretion with correction of plasma [Na+]. Erythrocyte cell volume was significantly increased in hyponatremic animals and intracellular [K+] and [Na+] both decreased equivalently, consistent with dilution of intracellular fluid by retained water. This model of SIADH differs significantly from those previously described, in that escape from the hydroosmotic effect of AVP and DDAVP does not occur in the absence of high urinary flow rates. The observed results using this model suggest that the retained water in SIADH primarily resides intracellularly following isotonic equilibration of extracellular fluid volume.