bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic concomitants of hypophagia during recovery from insulin-induced obesity in rats
Authors: Ramirez I. , Friedman M. I.
Published: December 2017

Rats were given daily injections of protamine-zinc insulin (PZI) that increased food intake and body weight. Termination of insulin treatment resulted in transient hypophagia and weight loss. Simultaneously with the weight loss, plasma levels of glycerol, free fatty acids, glucose, and ketones increased, whereas adipose tissue lipoprotein lipase activity and liver glycogen decreased. These changes in food intake and metabolism after termination of PZI treatment were accentuated in streptozotocin-diabetic rats. Two antilipolytic drugs (nicotinic acid and 3,5-dimethylpyrazole) blocked the elevation in plasma glycerol while having no effect on food intake. A 1-day fast after termination of insulin treatment equalized insulin-treated and control groups for plasma glycerol and ketones and reversed group differences in free fatty acids; the elevation in plasma glucose persisted despite starvation. Following starvation, previously PZI-treated rats ate less than controls on refeeding. The results show that enhanced lipolysis does not invariably accompany hypophagia during excess weight loss and suggest that a disturbance in carbohydrate metabolism or an increase in hepatic fatty acid oxidation may underlie this decrease in food intake.
Potassium effects on bone: comparison of two model systems
Authors: Krieger N. S. , Stern P. H.
Published: December 2017

Effects of elevated potassium on bone resorption and on the inhibition by ouabain of parathyroid hormone (PTH)-stimulated resorption were studied in neonatal mouse calvaria, fetal mouse limb bones, and fetal rat limb bones. Ouabain inhibited PTH-stimulated resorption, and K at least partially reversed the inhibition by ouabain in all three systems. However, in contrast to calvaria, neither limb bone system was stimulated to resorb by increased K. Although the reversal of ouabain inhibition in all three systems was likely mediated by an effect on Na-K-ATPase, the resorptive effect of K alone must occur by a different mechanism because it was seen only in the calvaria. The production of prostaglandins may play a partial role in the mechanism of the stimulation of Ca release from calvaria by K. Potassium (35 mM) stimulated production of PGE2 by calvaria but not by limb bones. Indomethacin inhibited the increase in PGE2 in calvaria and partially blocked the stimulated bone resorption observed in response to K. The fetal rat limb bone cultures also differed from the mouse calvaria in being more readily inhibited by increased osmolarity. Thus, secondary effects may be responsible for the variant responses of different bone tissues to certain stimuli.
Effects of PHI on hormonal secretion from perfused rat pancreas
Authors: Szecowka J. , Tendler D. , Efendic S.
Published: December 2017

Effects of the novel gastrointestinal polypeptide PHI with N-terminal histidine, C-terminal isoleucine amide, and 27 amino acids have been studied in isolated perfused rat pancreas. PHI increased the release of insulin, glucagon, and somatostatin. The amounts of these hormones released were strictly dependent on the prevailing glucose concentrations. In the absence of glucose, PHI (1 nmol/liter) stimulated glucagon release. In the presence of 4.4 and 6.7 mmol/liter glucose, the same dose of this peptide stimulated insulin and somatostatin release. In the presence of 16.7 mmol/liter glucose, only insulin secretion was increased by PHI. When arginine was used as a secretagogue, PHI (10 nmol/liter) potentiated secretion of insulin, glucagon, and somatostatin. Thus, PHI may take part in the regulation of the function of the pancreatic A, B, and D cells.
Ketone body turnover during and after exercise in overnight-fasted and starved humans
Authors: Fery F. , Balasse E. O.
Published: December 2017

The concentration of ketone bodies and their rate of transport (estimated with an infusion of beta-[14C]-hydroxybutyrate) were determined before, during, and after exercise in overnight-fasted and 3- to 5-day-fasted subjects who walked on a treadmill for 2 h at approximately 50% of their VO2max. In overnight-fasted subjects, exercise increased the rate of turnover (+125% after 2 h) and the metabolic clearance rate of ketone bodies whose concentration rose from 0.20 to 0.39 mM. Discontinuation of exercise was associated with a marked increase in ketone levels (+0.73 mM after 30 min of recovery) that was related to a further stimulation of ketogenesis (+19%) and to a marked drop of the metabolic clearance rate to below preexercise values. In sharp contrast with overnight-fasted subjects, starved subjects (with a resting ketone level averaging 5.7 mM) responded to work by a decrease in the turnover rate and in the concentration of ketones, their metabolic clearance rate remaining unchanged. Thus, the response of ketogenesis and muscular ketone uptake to exercise are both markedly influenced by the initial degree of fasting ketosis.
Glucose metabolism during lactation in the rat: quantitative and regulatory aspects
Authors: Burnol A. F. , Leturque A. , Ferre P. , Girard J.
Published: December 2017

Glucose metabolism was studied in anesthetized lactating rats in the postabsorptive state. Basal levels of blood glucose and plasma insulin were lower in 12-day-lactating rats than in age-matched nonlactating rats. When the pups were removed for 24 h, the maternal blood glucose level reached a value intermediate between lactating and nonlactating values, and the plasma insulin level was the same as in nonlactating rats. Glucose turnover was increased from 3 days postpartum on in lactating rats compared with nonlactating rats. At peak lactation (12-19 days) glucose turnover was 80% higher in lactating than in nonlactating rats. In the lactating rats weaned for 24 h, glucose turnover returned to the value of the nonlactating rats. Insulin secretion in response to an intravenous glucose load (IVGTT) was not modified in lactating rats compared with nonlactating rats but was increased threefold in weaned rats. This suggests that nonlactating tissues are insulin resistant during lactation. During euglycemic hyperinsulinemic clamp, glucose clearance was increased threefold in lactating and in nonlactating rats and twofold in weaned rats, suggesting that glucose metabolism in the mammary gland is affected by insulin. Measurement of lipogenesis gave direct evidence for the insulin responsiveness of the mammary gland and for the insulin resistance of adipose tissue during lactation.
Splanchnic glucose metabolism during leg exercise in 60-hour-fasted human subjects
Authors: Bjorkman O. , Eriksson L. S.
Published: December 2017

An increased mobilization of the hepatic glycogen is necessary for the maintenance of glucose homeostasis during exercise. To examine the effect of exercise on glucose metabolism when the hepatic glycogen stores are depleted, five prolonged-fasted (60-h, PF) subjects were investigated. Arterial concentrations and splanchnic exchange of glucose and gluconeogenic precursors were studied at rest and during exercise (40 min, 60% of VO2max) using the hepatic venous catheter technique. Five overnight-fasted subjects (OF) served as controls. In the resting state, arterial glucose concentration (3.0 +/- 0.2 mmol/liter) and splanchnic glucose output (SGO) (0.3 +/- 0.1 mmol/min) were 30 and 55% lower, respectively, in the PF than in the OF subjects. During exercise SGO rose in both groups, but the increase was smaller in the PF subjects so that at the end of work SGO (0.9 +/- 0.2 mmol/min) was only one-third of that in the OF group (2.5 +/- 0.4 mmol/min). During exercise in the PF state the arterial lactate concentration (5.0 +/- 1.1 mol/liter) and the splanchnic lactate uptake (1.1 +/- 0.3 mmol/min) were threefold and twofold higher, respectively, than in the OF state. In the PF state, the splanchnic uptake of gluconeogenic precursors could account for more than 80% of the splanchnic glucose production both at rest and during exercise. Despite the lower SGO in the PF state, blood glucose concentrations rose during exercise, indicating a diminished peripheral glucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Protein metabolism in skeletal muscle, diaphragm, and heart of diabetic rats
Authors: Pain V. M. , Albertse E. C. , Garlick P. J.
Published: December 2017

Rates of protein synthesis were measured in several muscle types in young streptozotocin-diabetic rats at different times after withdrawal of insulin therapy. Protein synthesis decreased in all types of muscle studied. In muscles with a substantial proportion of fast-twitch fibers (gastrocnemius and extensor digitorum longus), this decline was associated with falls in both protein synthesis-to-RNA and RNA-to-protein ratio, but in soleus and heart the effect could be explained entirely in terms of decreased ribosome concentration. Rates of protein degradation were calculated for heart, diaphragm, and gastrocnemius muscle from the changes in protein synthesis and protein content and were found in all cases to be elevated by 4 days of insulin withdrawal. However, measurements of protein synthesis and protein mass in the gastrocnemius muscle of a group of chronically diabetic rats indicated that in this condition, unlike in acute diabetes, the rate of protein degradation was depressed.
New perspectives on pancreatic islet glucokinase
Authors: Meglasson M. D. , Matschinsky F. M.
Published: December 2017

Control of blood sugar involves the complex interaction of the pancreatic glucose-sensing beta-cells with the liver, which serves as the primary site of glucose disposal after a meal. Glucokinase occupies an important role in controlling glucose phosphorylation and metabolism both in the liver and in pancreatic islets. In the beta-cells, glucokinase functions as pacemaker of glycolysis at physiological glucose levels. It determines the unique characteristics of islet hexose usage, that is, the rate, affinity, cooperativity, and anomeric discrimination of glucose metabolism. Because glycolysis controls hexose-induced insulin release, glucokinase is considered the best-qualified candidate for the elusive glucose sensor of beta-cells. A deficiency of glucokinase would disturb glucose homeostasis. Decreased islet glucokinase would diminish islet glycolysis and would result in a higher set point of beta-cells for glucose-induced insulin release. Decreased liver glucokinase would cause less efficient hepatic glucose disposal. Human maturity-onset diabetes (type II diabetes) has these characteristics. It is thus conceivable that certain forms of type II diabetes are due to a glucokinase deficiency.
Rat renal 25-hydroxyvitamin D3 1- and 24-hydroxylases: their in vivo regulation
Authors: Tanaka Y. , DeLuca H. F.
Published: December 2017

The effects of thyroparathyroidectomy, parathyroid hormone, 1,25-dihydroxyvitamin D3, dietary calcium, dietary phosphorus, age, and sex on the renal 25-hydroxyvitamin D3 1- and 24-hydroxylases measured in vitro in rats have been studied. Thyroparathyroidectomy of vitamin D-deficient rats abolishes 25-hydroxyvitamin D3 1-hydroxylase activity, and administration of bovine parathyroid extract to the thyroparathyroidectomized rat restores diminished 1-hydroxylase activity. Both suppression and restoration of the enzyme activities require many hours (18-24 h) independent of rapid changes in serum calcium and inorganic phosphorus levels in response to these manipulations. Administration of 1,25-dihydroxyvitamin D3 to vitamin D-deficient rats suppresses 25-hydroxyvitamin D3 1-hydroxylase activity and stimulates 25-hydroxyvitamin D3 24-hydroxylase activity within 48 h. Rats maintained on a low-calcium or a low-phosphorus diet with a daily supplement of 20 IU vitamin D3 show high 25-hydroxyvitamin D3 1-hydroxylase activity and low 24-hydroxylase activity as compared with rats similarly treated but fed a diet containing adequate calcium or adequate phosphorus. When vitamin D-sufficient rats having suppressed renal 25-hydroxyvitamin D3 1-hydroxylase activity are placed on a low-calcium vitamin D-deficient diet for 7 days, the 1-hydroxylase activity is greatly stimulated in 6-wk-old rats but much less so in rats with advancing age.
Evidence of two forms of hepatic extraction of parathyroid hormone in dogs in vivo
Authors: D'Amour P. , Huet P. M.
Published: December 2017

The fractional hepatic extraction (FHE) of oxidized 125iodine-labeled bovine parathyroid hormone, 125I-bPTH-(1-84), is dependent on the integrity of the 28-48 sequence of the bPTH structure. A second type of FHE, related to the biologically active core of the hormone, is suggested by liver adenylate cyclase activation or cAMP production by bPTH-(1-84) or bPTH-(1-34). We have thus compared the FHE of biologically active bPTH-(1-84), bPTH-(1-34), and of 125I-[Nle8, Nle18, Tyr34]bPTH-(1-34) amide with that of oxidized 125I-bPTH-(1-84). The preparations, together with reference substances, were injected into the portal vein of anesthetized dogs and dilution curves obtained by counting the radioactivity or assaying the immunoreactivity present in hepatic vein samples. FHE was calculated from these curves. Results were validated by gel chromatography analysis of the 125I-radioactive or immunoreactive preparation injected and recovered. In six dogs, the FHE of bPTH-(1-84) was 59.9 +/- 8.9%, 23% higher than the value of 39.6 +/- 9.3% obtained for 125I-bPTH-(1-84) injected simultaneously (P less than 0.0005). This difference was similar to the FHE of 125I-[Nle8, Nle18, Tyr34]bPTH-(1-34) amide (16.4 +/- 7.2%) and bPTH-(1-34) (23.5 +/- 10.4%) measured in seven dogs. Analysis of the various gel chromatography profiles revealed that the entire FHE process could be explained by extraction of the appropriate peak of each preparation; a small amount of fragment was also generated across the liver in the case of bPTH-(1-84) (1.6%) and 125I-[Nle8, Nle18, Tyr34]-bPTH-(1-34) amide (2.8%), with a larger quantity in the case of bPTH-(1-34) (17%).(ABSTRACT TRUNCATED AT 250 WORDS)
Beta-adrenergic stimulation of lipoprotein lipase in rat brown adipose tissue during acclimation to cold
Authors: Carneheim C. , Nedergaard J. , Cannon B.
Published: December 2017

Lipoprotein lipase activity in adult rats was investigated in animals subjected to cold and to different hormonal treatments. In contrast to changes in tissue wet weight and total protein content, which showed a lag time of about 1 day, lipoprotein lipase activity was markedly (fourfold) increased after only 4 h in the cold. Total lipoprotein lipase activity reached a plateau already after 1-3 days, whereas wet weight and protein content did not plateau until 3 wk. Neither insulin nor glucose injections could mimic the cold-induced increase in lipoprotein lipase activity seen after 4 h. However, the effect of norepinephrine injections was identical to the effect of cold. The beta-agonist isoprenaline was as effective as norepinephrine, whereas the alpha-agonist phenylephrine had no effect. The beta-antagonist propranolol inhibited the cold-induced increase in lipoprotein lipase activity. It is concluded that, in contrast to white adipose tissue, brown adipose tissue lipoprotein lipase is stimulated in vivo by a beta-adrenergic mechanism and that it is this beta-adrenergic mechanism that is responsible for the rapid recruitment of lipoprotein lipase during cold exposure.
In vivo stimulation of pancreatic hormone secretion by norepinephrine infusion in the dog
Authors: Ribes G. , Trimble E. R. , Blayac J. P. , Wollheim C. B. , Loubatieres-Mariani M. M.
Published: December 2017

Norepinephrine is generally regarded as an inhibitor of insulin release. It has been shown, however, that under hyperglycemic circumstances, norepinephrine infused at a high dose may also stimulate insulin secretion. The goals of this study were, under normoglycemic conditions, to confirm this stimulatory effect and to determine whether a beta-adrenergic mechanism or central neural pathways were involved. Secretion of pancreatic somatostatin and glucagon were also studied. Fasted, anesthetized dogs had norepinephrine (2 micrograms X kg-1 X min-1) infused into a peripheral vein for 60 min; blood was sampled from the pancreaticoduodenal vein. Norepinephrine stimulated insulin, somatostatin, and glucagon secretion without significant changes in either blood glucose concentration or pancreaticoduodenal venous blood flow. The stimulatory effect of norepinephrine on the three hormones was abolished by propranolol pretreatment, thus implicating a beta-adrenergic mechanism. Because bilateral cervical vagotomy prevented stimulation of insulin secretion by norepinephrine, central neural pathways must have been involved in the stimulatory process. However, norepinephrine-induced glucagon secretion was not decreased by vagotomy, showing that the stimulation was due to either a direct action on the pancreatic A cell or of a central pathway not mediated via the vagus nerve. Norepinephrine-induced somatostatin secretion was partly reduced by vagotomy, indicating that several mechanisms could be implicated.
Abnormal D cell secretion in alloxan-diabetes: influence by drug and aberrant metabolism
Authors: Grill V. , Efendic S.
Published: December 2017

Abnormalities of somatostatin secretion in diabetes may be secondary to B cell damage with resulting insulinopenia or other effects of diabetogenic agents, including toxicity toward the somatostatin-producing D cells. These possibilities were evaluated in isolated perfused pancreas from normal and alloxan-diabetic rats. In normal rats 3-isobutyl-1-methylxanthine (IBMX, 1 mM), alpha-ketoisocaproic acid (KIC, 5 mM), D-glucose (27 mM), and D-glyceraldehyde (5 mM) stimulated somatostatin release. In diabetic rats 3 days after alloxan, IBMX and KIC elicited somatostatin release, whereas glucose or glyceraldehyde were without effect. In diabetic rats 14 days after alloxan, an otherwise (in normal and 3-day diabetic rats) nonstimulatory concentration of IBMX (0.05 mM) markedly stimulated somatostatin release, whereas as in 3-day diabetic rats glucose was ineffective. Insulin treatment for 2 days did not affect the somatostatin response to glucose in normal rats, did not restore a somatostatin response to glucose 3 days after alloxan, but partially restored (P less than 0.01) a response to glucose (28% of normal) 14 days after alloxan. Insulin in vitro (1 mU/ml, 20 min) failed to restore a glucose effect. Administration of alloxan (1.0 mM) for 5 min to pancreases from normal rats inhibited glucose-induced somatostatin response from 1,562 +/- 401 to 206 +/- 83 pg/15 min (P less than 0.01), whereas the response to IBMX (1 mM) was not significantly decreased. Following different time courses, both an effect of alloxan and of metabolic derangement inhibit somatostatin responses to glucose in alloxan diabetes.
Distinguishing effects of anemia and muscle iron deficiency on exercise bioenergetics in the rat
Authors: Davies K. J. , Donovan C. M. , Refino C. J. , Brooks G. A. , Packer L. , Dallman P. R.
Published: December 2017

Three weeks of dietary iron deficiency in weanling rats resulted in anemia (Hb, 3.9 vs. 14.2 g/dl in controls) and decreased oxidative capacities of skeletal muscle (as much as 90% below control values). Whole-animal maximal O2 consumption (VO2max), measured in a brief treadmill run of progressively increasing work load, was approximately 50% lower for iron-deficient rats than for controls, and maximal endurance capacity (time to exhaustion in a separate treadmill run at a constant, sub-Vo2max work load) was 90% lower for iron-deficient rats than for controls. Exchange transfusion, with packed erythrocytes or plasma, was used to adjust Hb to an intermediate concentration of approximately 9.5 g/dl in both iron-deficient and and control rats. This procedure corrected the Vo2max of iron-deficient rats to within 15% of control values, whereas endurance capacity showed no improvement. Our experimental dissociation of Vo2max and endurance capacity provides further evidence that Vo2max is not the sole determinant of endurance. We propose that defects in Vo2max during iron deficiency result primarily from diminished O2 delivery, whereas decreased endurance capacity reflects impaired muscle mitochondrial function.
Islet function and stress hyperglycemia: plasma glucose and epinephrine interaction
Authors: Halter J. B. , Beard J. C. , Porte D.
Published: December 2017

Catecholamines and a number of other hormones released during stress states contribute to the development of hyperglycemia by directly stimulating glucose production and interfering with tissue disposal of glucose. However, hyperglycemia stimulates the secretion of insulin and inhibits the secretion of glucagon, effects that will diminish the degree of hyperglycemia resulting from direct actions of stress hormones on glucose production and disposal. The key additional role of catecholamines in the development of stress hyperglycemia is interference with the normal feedback control of insulin and glucagon secretion by circulating glucose levels. Although pancreatic islet responses to hyperglycemia may be modulated by catecholamines, any increase of insulin secretion or suppression of glucagon secretion that does occur may be important for limiting the degree of elevation of circulating glucose that results. Thus, plasma insulin and glucagon levels during stress states will reflect the interaction between the opposing effects of hyperglycemia and catecholamines. Diabetic patients who have impaired islet responses to glucose will be particularly prone to the development of marked hyperglycemia during stress states because they may be unable to respond to the influence of hyperglycemia in counteracting adrenergic inhibition of insulin secretion and stimulation of glucagon secretion.
Roles of glucagon and epinephrine in hypoglycemic and nonhypoglycemic glucose counterregulation in humans
Authors: Cryer P. E. , Tse T. F. , Clutter W. E. , Shah S. D.
Published: December 2017

Studies of two models of human glucose counterregulation, glucose recovery from insulin-induced hypoglycemia and the transition from exogenous glucose delivery to endogenous glucose production late after glucose ingestion, indicate that the principles of rapid hypoglycemic and nonhypoglycemic glucose counterregulation in these models are the same. 1) Neither is solely explicable on the basis of dissipation of insulin; 2) glucagon plays a primary counterregulatory role in both; 3) epinephrine compensates largely for deficient glucagon secretion in both; and 4) counterregulation fails to occur only in the absence of both glucagon and epinephrine in both. Thus, prevention as well as correction of hypoglycemia is effectively accomplished by redundant glucose counterregulatory systems, primarily glucagon and secondarily epinephrine, coupled with dissipation of insulin in humans. Other hormones, neural mechanisms, or autoregulation may be involved but need not be invoked and are not sufficiently potent to prevent or correct hypoglycemia when both of the key glucose counterregulatory hormones, glucagon and epinephrine, are deficient. Although confirmed in that they predict the impact of disease-related deficiencies of glucagon, epinephrine, or both, the extent to which these principles can be generalized to additional models of glucose counterregulation remains to be established. However, they provide a basis for plausible, testable hypotheses concerning the physiology and pathophysiology of glucose counterregulation.
Excretion and metabolism of dopa and dopamine by isolated perfused rat kidney
Authors: Suzuki H. , Nakane H. , Kawamura M. , Yoshizawa M. , Takeshita E. , Saruta T.
Published: December 2017

The renal metabolism and handling of dopa and dopamine were studied with the use of the isolated perfused rat kidney to elucidate the source of urinary dopamine. Dopa added to the perfusate was rapidly metabolized, and a significant amount of urinary dopamine excretion was observed, whereas dopa was not detected in the urine. When the perfusate dopa concentration was near the plasma dopa concentration in normal rats, urinary dopamine excretion was comparable with physiological values. Carbidopa, a dopa decarboxylase blocker, added to the perfusate markedly reduced the urinary excretion of dopamine. When the physiological concentration of dopamine was added to the medium, the perfusate dopamine rapidly decreased and urinary dopamine excretion was much less than that seen in normal rats. In studies with nonfiltering kidneys, a marked decrease of dopa and slight increase of dopamine in the perfusate were observed. It is suggested that the process of glomerular filtration and tubular reuptake of dopa is not essential for renal dopamine formation. These data indicate that urinary free dopamine is mainly derived from plasma dopa, which is converted by dopa decarboxylase in the kidney.
Multiplicative interaction between angiotensin II and K concentration in stimulation of aldosterone
Authors: Young D. B. , Smith M. J. , Jackson T. E. , Scott R. E.
Published: December 2017

The interaction of angiotensin II and plasma K concentration in stimulating aldosterone secretion was studied in a group of six dogs by determining the aldosterone response to three levels of angiotensin II while the dogs were maintained on three levels of K intake. The levels of angiotensin were 1) the endogenous level, 2) the concentration resulting from infusion of 5 ng X kg-1 X min-1, and 3) the concentration resulting from infusion of 10 ng X kg-1 X min-1. Each level was maintained for 5 days. The three rates of K intake were 10, 100, and 200 meq/day, each maintained for 3 wk. Data were analyzed from days 1, 2, and 5 of the angiotensin infusion periods. The regressions obtained from plotting plasma K (PK) versus aldosterone concentration on day 5 of each level of infusion were 1) for no infusion (endogenous PRA = 0.4 to 0.5 ng ANG I X ml-1 X h-1), aldosterone = 5.04 X PK - 16.56; 2) for 5 ng X kg-1 X min-1 infusion, aldosterone = 12.20 X PK - 39.09; and 3) for 10 ng X kg-1 X min-1 infusion, aldosterone = 35.50 X Pk - 119.31. Each regression was significantly different (P less than 0.001) from the other two. The plasma K axis intercepts, which are the points at which aldosterone secretion is zero, were 3.29, 3.20, and 3.36 for the regression from the 0, 5, and 10 ng X kg-1 X min-1 infusion rates, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Excess in vitro prolactin secretion by pituitary cells from ovariectomized old rats
Authors: Haji M. , Roth G. S. , Blackman M. R.
Published: December 2017

Various in vivo and in vitro pituitary lactotropic and gonadotropic functions were measured in mature (6-7 mo, normally cycling) and old (24 mo, constant diestrus) female Wistar rats. Serum prolactin (PRL) levels were higher (P less than 0.001), whereas luteinizing hormone (LH) values were similar (P greater than 0.05) in old versus mature rats both before and 3 days after ovariectomy. Serum PRL levels decreased significantly (P less than 0.005) postovariectomy only in the mature rats. The in vitro release of PRL and LH was measured for 4 days in primary adenohypophyseal cell cultures from the ovariectomized rats. Both basal and 17 beta-estradiol (E2)-stimulated PRL release (P less than 0.001) and production (P less than 0.005) were greater by cells from old rats. In contrast, both basal release and E2-stimulated LH release were greater (P less than 0.001) by cells from mature rats. Peak PRL release by cells from both old and mature rats occurred after exposure to E2 doses 1/100th of those required for peak LH release. These data support the hypothesis that intrinsic derangements in anterior pituitary function contribute to the reproductive decline in aging female rats and that different pituitary cell types exhibit discordant age changes in estrogenic sensitivity.
Modulation of gonadotropin secretion by Sertoli cell inhibin, LHRH, and sex steroids
Authors: Massicotte J. , Lagace L. , Labrie F. , Dorrington J. H.
Published: December 2017

Sertoli cell culture media (SCM) from 10-, 20-, 30-, 35-, and 40-day-old male Wistar rats were assayed to determine the inhibin activity in anterior pituitary cells in culture. In agreement with previous data, SCM did not affect the luteinizing hormone (LH) spontaneous release at all ages studied, whereas it inhibited specifically follicle-stimulating hormone (FSH) spontaneous release by 40% for the 40-day-old rats. Younger animals (10-, 20-, and 30-day-old) showed a 60% inhibition of the FSH basal release. The inhibin activity was also different at all stages studied, the IC50 being markedly displaced to the right as the age increased, leading to a fivefold difference between 10- and 30- to 40-day-old rats. The same pattern was observed when the LH and FSH responses to 0.3 nM LH-releasing hormone (LHRH) were studied. SCM from 35-day-old rats did not alter total LH, whereas total FSH was markedly reduced, thus suggesting a reduced FSH synthesis in the presence of inhibin. SCM exerts an additive inhibitory effect with dihydrotestosterone on the LH response to LHRH, whereas it reverses the stimulatory effect of the androgen on spontaneous and LHRH-induced FSH release. Moreover, SCM reversed the stimulatory effect of 17 beta-estradiol on both spontaneous and LHRH-induced LH and FSH release, whereas the stimulatory effect of progesterone on FSH release was 50-80% inhibited. The present data show that inhibin activity of Sertoli cell origin can exert marked interactions with sex steroids in the control of gonadotropin secretion. These data also demonstrate that the inhibin component is an important factor in sexual maturation of the rat and that high FSH levels of 10-day-old rats could suggest a modulation by a nonandrogenic factor of gonadotropin secretion in developing rats.
Insulin stimulates Pi transport in brush border vesicles from proximal tubular segments
Authors: Hammerman M. R. , Rogers S. , Hansen V. A. , Gavin J. R.
Published: December 2017

Induction of hyperinsulinemia in dogs results in enhanced reabsorption of Pi from glomerular filtrate in the renal proximal tubule. To determine whether this may be a direct action of insulin mediated by altered transport characteristics of the proximal tubular brush border membrane, we measured Na+-dependent 32Pi transport in brush border membrane vesicles prepared from isolated proximal tubular segments originating from dog kidney that had been incubated with or without insulin. Specific high affinity binding sites for insulin were detected in proximal tubular segments. Increased initial rates (15 s) of Na+-dependent 32Pi transport were measured in brush border vesicles prepared from segments that had been incubated with insulin. This effect of insulin was concentration dependent over the range of 10(-10) to 10(-6) M insulin. These studies demonstrate the feasibility of using brush border vesicles prepared from proximal tubular segments to study solute transport. Our findings suggest that insulin-induced increased Pi reabsorption in the proximal tubule is mediated by a direct action of insulin on the proximal tubular cell, which results in increased Na+-Pi cotransport across the brush border membrane.
Stimulatory effect of norepinephrine on ketogenesis in normal and insulin-deficient humans
Authors: Keller U. , Gerber P. P. , Stauffacher W.
Published: December 2017

Elevation of plasma norepinephrine concentrations to stress levels (1,800 pg/ml) resulted in normal subjects in a significant increase in ketone body production by 155% (determined by use of [14C]acetoacetate infusions), in a decrease of the metabolic clearance rate by 38%, hyperketonemia, and in increased plasma free fatty acid (FFA) levels by 57% after 75 min. Norepinephrine infusion during somatostatin-induced insulin deficiency resulted in an augmented and sustained increase in ketone body concentrations due to increased production and decreased peripheral clearance of ketone bodies. Norepinephrine's stimulatory effect on lipolysis waned with time, and its effect on ketogenesis in normal subjects was greater than its influence on plasma FFA levels, and thus presumably on hepatic FFA uptake, suggesting a direct stimulatory effect on hepatic ketogenesis. The data demonstrate that in normal humans the hyperketonemic effect of elevated plasma norepinephrine concentrations results from a combination of three factors: increased ketone body production from augmented FFA supply to the liver; accelerated hepatic ketogenesis; and modestly decreased metabolic clearance of ketone bodies. Acute insulin deficiency augments all these effects and results in progressive ketosis.
Influence of beta-hydroxybutyrate infusion on glucose and free fatty acid metabolism in dogs
Authors: Shaw J. H. , Wolfe R. R.
Published: December 2017

We have investigated the effect of infusion of DL-beta-hydroxybutyrate (BOHB) (30 mumol X kg-1 X min-1) on glucose and free fatty acid (FFA) metabolism by means of the primed constant infusion of [U-14C]glucose and [1,2-13C]palmitic acid. The role of the hormonal response to the ketone infusion was assessed by controlling the hormone levels pharmacologically. In one group hormones were not controlled, while in the other two groups insulin and glucagon were maintained at constant levels by infusion of somatostatin, insulin, and glucagon at constant rates. In one of these hormonally controlled groups, combined alpha- and beta-adrenergic blockade was also employed. BOHB infusion increased total ketone concentration approximately 10-fold and, when hormones were not controlled, induced a significant increase in glucagon concentration. Regardless of hormonal status, elevation of the ketone levels decreased the rate of glucose production and FFA appearance. Glucose oxidation decreased in proportion to the reduction in the rate of glucose uptake in all groups. When sympathetic activity was not blocked an increase in the percent of FFA uptake oxidized enabled the percent CO2 production from FFA oxidation to remain constant despite the decrease in FFA uptake. However, when sympathetic activity was blocked the increase in the percent of FFA uptake oxidized observed in the other groups was prevented. We conclude from these studies that an elevation in ketone levels directly affects glucose and FFA metabolism independent of changes in insulin and glucagon levels and sympathetic activity.
Suppression of endotoxin-induced corticosterone secretion in rats by H1-antihistamine
Authors: Suzuki S. , Nakano K.
Published: December 2017

Corticosterone (CS) secretion is stimulated in rats by an intraperitoneal injection of bacterial lipopolysaccharide (LPS) or by subjecting the animals to immobilization stress. LPS injection caused a significant increase in the lung histamine level and a sharp reduction in the number of intact peritoneal mast cells. Injection of compound 48/80, a histamine liberator, provoked an increase in the histamine levels of the blood and lung and a decrease in the number of intact peritoneal mast cells with a concomitant increase in CS secretion. Administration of histamine, at a dose of 10 mg/kg, induced a marked increase in CS release. LPS-induced CS secretion was attenuated by pretreatment with an H1-antihistamine, promethazine (PMZ), whereas an H2-antihistamine, metiamide, had no effect. In contrast, PMZ was ineffective on CS release provoked by immobilization stress. These results suggest that LPS-induced CS release is mediated, in part, by histamine released in the peripheral tissues, whereas an immobilization stress-induced increase is not mediated by the amine.
Effects of prior adrenalectomy on postpneumonectomy lung growth in the rat
Authors: Bennett R. A. , Colony P. C. , Addison J. L. , Rannels D. E.
Published: December 2017

The effects of adrenalectomy, with and without subsequent glucocorticoid replacement therapy, on postpneumonectomy compensatory lung growth in the rat were investigated. Male Sprague-Dawley rats (200-230 g) were subjected to no operation (UNOP), left pneumonectomy (PNX), or PNX preceded by bilateral adrenalectomy 5 days earlier (ADX/PNX). At 14 days post-PNX, when compensatory lung growth is normally complete in 200-g rats, right lung (RL) dry weights of PNX (263 +/- 6 mg, n = 26) and ADX/PNX (334 +/- 13 mg, n = 25) rats were increased 58 and 101%, respectively, relative to UNOP controls (166 +/- 5 mg, n = 10). Increases in total DNA, RNA, and protein in the right lungs of PNX and ADX/PNX rats occurred in proportion to RL dry mass. The increase in all parameters examined in PNX and ADX/PNX rats at 7 days post-PNX was half that at 14 days, indicating linear lung growth in both treatment groups. The stimulatory effect of ADX on lung growth was blocked by hydrocortisone acetate (HCA), administered intraperitoneally in daily doses of 5 mg/kg, beginning on the day of PNX. The RL dry weights of HCA-treated ADX/PNX rats (241 +/- 7 mg, n = 10) did not differ significantly from the corresponding value in PNX rats (270 +/- 14 mg, n = 7). The lower RL weights in the HCA-treated rats resulted from an inhibition of cell division, as evidenced by the total RL DNA content, which was similar to that in PNX animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanisms of the defect in cardiac myofibrillar function during diabetes
Authors: Pierce G. N. , Dhalla N. S.
Published: December 2017

Diabetes was induced in rats by an intravenous injection of streptozotocin (65 mg/kg body wt), and animals were killed 8 wk later. Some animals were maintained in a diabetic state for 6 wk and then given 2 wk of insulin treatment in vivo. Myofibrils were isolated and ATPase activities measured. Mg2+-ATPase and Ca2+-stimulated ATPase activities were depressed in diabetic rat hearts in comparison to control; insulin treatment normalized these activities. The depression in myofibrillar ATPases was of gradual onset as no changes were detected 2 wk after inducing diabetes. Treatment of diabetic animals with thyroid hormone did not restore changes in myofibrillar ATPase activities. Marker enzyme activities did not reveal any detectable contamination by cardiac membranes. Mg2+-ATPase activity of myofibrillar preparations from control and diabetic hearts responded differently to N-ethylmaleimide modification. Furthermore, myofibrillar sulfhydryl reactivity to 5,5'-dithiobis(2-nitrobenzoic acid) was significantly depressed in diabetic preparations in comparison to control and insulin-treated diabetic animals. These results suggest that the defect in myofibrillar ATPase activities in chronic diabetes may be due to some modification of sulfhydryl groups.
Compensatory adrenal cortical growth is inhibited by sympathectomy
Authors: Kleitman N. , Holzwarth M. A.
Published: December 2017

After the surgical removal of one adrenal gland, the cortex of the remaining adrenal gland increases in size. This compensatory adrenal growth is characterized by increased weight and DNA content of the remaining adrenal 72 h after unilateral adrenalectomy. In these experiments, chemical sympathectomy prevented compensatory adrenal growth. In rats sympathectomized by neonatal injections of 6-hydroxydopamine or guanethidine and unilaterally adrenalectomized at 40 days of age, the compensatory increase in weight in the remaining gland was attenuated (relative to a vehicle-injected control group) and not accompanied by the usual increase in DNA content. Augmented RNA content was observed after unilateral adrenalectomy in sympathectomized as well as vehicle-injected animals; presumably this reflects increased steroidogenesis because, despite the loss of one adrenal, the rats maintained normal plasma corticosterone and aldosterone levels (relative to the sham-adrenalectomized group). The sympathectomy procedures themselves did not significantly alter adrenal weight, adrenal nucleic acid content, or plasma aldosterone relative to vehicle-injected control levels; however, plasma corticosterone levels were significantly reduced. We conclude that the sympathetic nervous system mediates the adrenal cortical cell proliferation that occurs after unilateral adrenalectomy.
Does food restriction retard aging by reducing the metabolic rate?
Authors: McCarter R. , Masoro E. J. , Yu B. P.
Published: December 2017

Metabolic rate was determined by measuring O2 consumption in two groups of 6-mo-old male rats fed ad libitum (group 1) or maintained on a life-prolonging food-restriction regimen for 4.5 mo (group 2). These measurements were made continuously for 23.75 h under conditions nearly identical to those of the daily life of the rats. The metabolic rate per kilogram lean body mass was the same for both groups, a finding contrary to the hypothesis that food restriction retards the aging process and prolongs life by slowing the metabolic rate per unit of metabolic mass. This and our previous work strongly suggest that the classic views of the action of food restriction on aging must be re-evaluated because retardation of the aging process can occur without the restriction of calories or any other nutrient per unit of lean body mass. The long held belief that reducing food intake lowers the metabolic rate per unit of metabolic mass may be true in short-term dietary programs but appears not to be true when a significant portion of the life span is involved.
Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man
Authors: Astrup A. , Bulow J. , Madsen J. , Christensen N. J.
Published: December 2017

This investigation was performed to examine the role of brown adipose tissue (BAT) in thermogenesis induced by ephedrine in man. Light microscopy of biopsies from necropsy cases showed BAT to occur most frequently in the perirenal fat. Perirenal BAT thermogenesis was investigated in five lean men before and during stimulation with 1 mg ephedrine orally X kg body wt-1. Perirenal BAT thermogenesis was assessed by continuous measurements of local temperature and blood flow with the 133xenon clearance method. In the same study the effect of ephedrine on skeletal muscle oxygen consumption was estimated by measurements of leg blood flow and arteriovenous oxygen difference. The perirenal adipose tissue blood flow increased approximately twofold, whereas the local temperature increased approximately 0.1 degrees C on an average. Assuming that man possesses 700 g of BAT with a similar thermogenic capacity, this tissue contributed only 10 ml X min-1 to the 40 ml X min-1 increase in oxygen consumption in the subject whose perirenal BAT showed the most pronounced response to ephedrine. The leg oxygen consumption increased on an average 60% after ephedrine. By extrapolation of this value to whole body skeletal muscle, approximately 50% of the increase in oxygen consumption induced by ephedrine may take place in skeletal muscle. It is concluded that skeletal muscle is a tissue of importance with respect to the thermogenic effect of sympathomimetics in man, whereas the results do not support a major role for perirenal BAT.
Ca antagonists do not alter aldosterone secretion during established Na depletion
Authors: Johnson E. I. , McDougall J. G. , Coghlan J. P. , Denton D. A. , Hardy K. J. , Scoggins B. A. , Wright R. D.
Published: December 2017

Conscious sheep whose sole adrenal gland had been transplanted to the neck to allow access to the adrenal vasculature were used to study the effect of calcium antagonists on aldosterone secretion. All animals were sodium depleted by uncompensated loss of parotid saliva. The drugs EDTA, verapamil, methoxyverapamil, nisoldipine, lanthanum, propylmethylenedioxyindene, and ryanodine were infused on separate occasions in three or four increasing dose levels. All infusions were made to produce known concentrations directly into the adrenal arterial blood supply. None of these infusions had any significant effect on aldosterone secretion rate, cortisol secretion rate, and little or no effect on plasma [Na], [K], or blood pressure. At high infusion rates some agents (verapamil, methoxyverapamil) caused tachycardia. In contrast, angiotensin II stimulation of aldosterone secretion is inhibited by both verapamil and nisoldipine. The data demonstrate that the sustained elevation of aldosterone secretion caused by sodium depletion is not dependent on a sustained alteration in transmembrane calcium flux. Furthermore, if circulating angiotensin II is the primary stimulus to aldosterone during sodium depletion, its mechanism of action appears to switch to one which is not dependent on calcium alone.
Modification of renin isoelectric heterogeneity in Goldblatt hypertensive rat
Authors: Sessler F. M. , Malvin R. L.
Published: December 2017

Six forms of renin have been described in rat kidney. Different stimuli resulted in secretion of unique profiles of those forms. We studied their storage and secretion in the two-kidney, one-clip Goldblatt hypertensive rat (GHR). Renal venous blood, kidney homogenates, and incubation media from cortical slices were subjected to isoelectric focusing. In all samples tested, six peaks of renin activity were found with isoelectric points at pH 5.90, 5.70, 5.40, 5.20, 5.00, and 4.80. The quantity of renin activity for each form was expressed as a percentage of the total recovered from the gel. In control kidneys the profile of renin stored and that released by in vitro slices were similar. However, in plasma, the percentage of renin focusing at the more basic pH was decreased. This is in agreement with other work showing that the liver removes the more basic forms more rapidly than the acidic forms. The clipped kidney of GHR secreted, both in vivo and in vitro, a profile of renin forms that was significantly different from the control kidney. The difference was expressed by an increase in the secretion of the more acidic forms by the clipped kidney. It is hypothesized that changes in the secretory profile of renin may reflect changes in storage and synthesis of those forms.
Metabolic clearance of angiotensin II in pregnant and nonpregnant sheep
Authors: Naden R. P. , Coultrup S. , Arant B. S. , Rosenfeld C. R.
Published: December 2017

Reduced vascular responsiveness to infused angiotensin II (ANG II) has been observed during pregnancy. It has been proposed that infusions produce lower circulating concentrations of ANG II in pregnancy, due to an increase in the metabolic clearance rate of ANG II (MCRangii). We have evaluated the MCRangii and the arterial plasma concentrations of ANG II during constant infusions of 1.15 micrograms ANG II/min into chronically instrumented pregnant (n = 6) and nonpregnant (n = 9) sheep. Although the pressor responses were significantly less in the pregnant than in the nonpregnant sheep (17.5 +/- 0.5 vs. 34.9 +/- 3.2 mmHg, P less than 0.001), the values for MCRangii were not different: 56.2 +/- 6.3 ml X min-1 X kg-1 in nonpregnant and 55.9 +/- 4.3 ml X min-1 X kg-1 in pregnant sheep. The steady-state plasma ANG II concentrations during the infusions were slightly less in pregnant than in nonpregnant sheep (388 +/- 36 vs. 454 +/- 36 pg/ml); however, this difference would be responsible for only a 2-mmHg reduction in the pressor response. We conclude that the reduced pressor response to infused ANG II in pregnancy is not due to an increase in MCRangii nor to lower plasma ANG II concentrations.