bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of a direct alpha-adrenergic effect of epinephrine on glucose production in human subjects
Authors: Best J. D. , Ward W. K. , Pfeifer M. A. , Halter J. B.
Published: December 2017

To determine whether alpha-adrenergic stimulation can directly increase glucose production in humans, we infused epinephrine plus propranolol in six normal subjects. The contribution of pancreatic islet effects was eliminated by the infusion of somatostatin. Despite high levels of epinephrine (1,234 +/- 255 pg/ml; mean +/- SE), plasma glucose fell from 85 + 1 to 71 +/- 7 mg/dl. Glucose production rate fell from 1.88 +/- 0.06 to 1.50 +/- 0.16 mg X kg-1 X min-1. During control studies in the same subjects (propranolol and somatostatin without epinephrine), plasma glucose fell from 87 +/- 1 to 75 +/- 3 mg/dl and glucose production fell from 1.93 +/- 0.10 to 1.58 +/- 0.13 mg X kg-1 X min-1. Thus, under conditions of suppressed insulin and falling glucose levels, both of which favor a positive response, a high level of alpha-adrenergic stimulation failed to directly increase glucose production. To ensure that the liver was not refractory to other stimuli, glucagon was administered during infusion of epinephrine and propranolol. In these studies, plasma glucose rose to 175 +/- 20 mg/dl and glucose production plateaued at 3.71 +/- 0.30 mg X kg-1 X min-1 (n = 7). These findings were similar to the effects of propranolol, somatostatin, and glucagon without epinephrine on plasma glucose (196 +/- 15 mg/dl) and glucose production (3.65 +/- 0.29 mg X kg-1 X min-1). Thus, although the liver remained responsive to glucagon during alpha-adrenergic stimulation, no alpha-adrenergic augmentation of glucose production was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Estrogen-like stimulation of uterine ornithine decarboxylase by cholera toxin
Authors: Webster R. A. , Zaloudek C. J. , Inman B. C. , Stewart P. J.
Published: December 2017

Cholera toxin administered by intrauterine injection to ovariectomized rats increased uterine ornithine decarboxylase activity as much as systemic estradiol at 4 h after treatment. At 45-60 min after treatment, however, cholera toxin did not increase nuclear estrogen receptor or stimulate synthesis of the uterine "induced protein," which is closely correlated with nuclear receptor, whereas estradiol caused substantial increases in both nuclear receptor and induced protein synthesis. Intrauterine injection of cholera toxin also produced an estrogen-like elevation of the uterine protein/DNA ratio at 24 h. Because both cholera toxin and estradiol are known to increase vascular permeability, our results support the hypothesis that some uterine effects of estradiol are not mediated by receptor-genome interaction but involve another mechanism that is associated with increased vascular permeability.
A dual role of calcium in release of somatostatin from canine gastric antral mucosa
Authors: Pittenger G. , Vinik A. I. , Fiddian-Green R. G. , Wagner L.
Published: December 2017

We have examined the factors regulating the mucosal release of somatostatin-like immuno-reactivity (SRIF-LI) from 1-cm2 sheets of isolated canine gastric antral mucosa mounted in a Ussing chamber. SRIF-LI was released predominantly into the luminal perfusate, was maximal at pH 2.5, 1,987 +/- 319 pg X ml-1 X h-1, and reached a nadir at pH 6.0 of 89 +/- 24 pg X ml-1 X h-1. Increasing extracellular Ca2+ to 10 mM stimulated the release of SRIF-LI at both high and low pH. The Ca2+ ionophore A23187 had no apparent effect at either pH 2.5 or 7.0. LaCl3 stimulated the release of SRIF-LI at pH 7.0 but not at pH 2.5. Ouabain and TMB-8 had no significant effect on the release of SRIF-LI. At pH 7.0, trifluoperazine (TFP) stimulated release of SRIF-LI (80 +/- 10 pg X ml-1 X h-1). EGTA stimulated release of SRIF-LI at pH 2.5 (1,134 +/- 137 pg X ml-1 X h-1) and at pH 7.0 (300 +/- 57 pg X ml-1 X h-1), which was reversed by replacement of Ca2+ (22 +/- 6 pg X ml-1 X h-1). Thus Ca2+ appears to exert a dual effect on the release of SRIF-LI: both an increase and depletion of extracellular Ca2+ release SRIF-LI.
Effect of age and gene dosage on brown adipose tissue of Zucker obese fa/fa rats
Authors: York D. , Holt S. , Rothwell N. , Stock M.
Published: December 2017

Experiments were performed to investigate the effect of age and genotype on brown adipose tissue thermogenesis in Zucker rats. Specific [3H]GDP binding to interscapular brown adipose tissue mitochondria ( IBATM ) was reduced in 14-day-old preobese fa/fa rats and remained lower after weaning. A gene-dosage effect of the recessive fa gene was observed in 8- to 10-wk-old rats in both IBATM [3H]GDP binding and the thermic effect of a balanced meal (50 kJ Complan ), measured by indirect calorimetry. In each case the heterozygote (Fa/fa) group had a value intermediate between those of obese (fa/fa) and the homozygous lean (Fa/Fa) groups. Norepinephrine increased IBATM [3H]GDP binding to similar levels in lean (Fa/fa) and obese (fa/fa) rats and induced similar increases in oxygen consumption in Fa/Fa, Fa/fa, and fa/fa rats. It is concluded that the impaired, diet-related brown adipose tissue thermogenesis is closely related to the primary gene defect in the obese rat. This defect may result from misregulation of the autonomic nervous system.
Insulin resistance in older rats
Authors: Narimiya M. , Azhar S. , Dolkas C. B. , Mondon C. E. , Sims C. , Wright D. W. , Reaven G. M.
Published: December 2017

Insulin-stimulated glucose utilization was estimated in vivo in 1.5-, 4-, and 12-mo-old rats with an insulin suppression test wherein the height of the steady-state plasma glucose ( SSPG ) concentration, at similar steady-state plasma insulin levels, provides a direct reflection of the efficiency of insulin-stimulated glucose disposal. In parallel studies, the effect of age on in vitro insulin-stimulated glucose uptake was assessed in perfused hindlimb preparations. In addition, changes in the activity of enzymes that regulate muscle glycolysis, glycogenesis, and glycogenolysis were determined in isolated soleus muscle. The results indicated that rats got heavier as they became older, and changes in weight were associated with parallel increases in mean (+/- SE) SSPG concentrations as rats grew from 1.5 (56 +/- 3 mg/dl) to 4 (172 +/- 6 mg/dl) to 12 mo of age (194 +/- 8 mg/dl). The age-related decline in in vivo insulin action was associated with a reduction in insulin action on muscle, and maximal insulin-stimulated glucose uptake by perfused hindlimbs of 12-mo-old rats was approximately 50% of the value seen with perfused hindlimbs from 1.5-mo-old rats. Soleus muscle enzyme activity also varied with age, with significant increases in glycogen synthase and decreases in glycogen phosphorylase documented. Furthermore, muscle glycogen phosphorylase activity, which fell during an insulin infusion in 1.5-mo-old rats, did not change when 12-mo-old rats were infused at comparable insulin levels. Finally, glycogen content was significantly increased (P less than 0.01) in soleus muscle from 12-mo-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in ovine fetal hindlimb amino acid metabolism during maternal fasting
Authors: Liechty E. A. , Lemons J. A.
Published: December 2017

The flux of various substrates across the ovine fetal and maternal hindlimbs was measured in the fed state and after 5 days of maternal fasting. Whole blood concentrations of glucose, oxygen, ammonia, and six amino acids (glutamate, glutamine, alanine, valine, isoleucine, and leucine) were determined in the fetal and maternal femoral artery and distal inferior vena cava in 15 chronic animal preparations. During fasting the fetal arterial glucose concentration fell by 40% (from 0.828 to 0.494 mM), and the arteriovenous concentration difference decreased by 30% (from 0.148 to 0.099 mM). Similar changes were noted in maternal blood. Fetal oxygen concentrations remained similar between the fed and fasted state, and the fetal arteriovenous oxygen concentration difference increased slightly from 0.861 to 1.02 mM. The glucose oxygen quotient decreased in the fetus from 1.20 to 0.621. In addition, significant changes occurred in the net balance of several amino acids during the fasted state. Both alanine and glutamine, which demonstrated a positive uptake by the fetal hindlimb during the fed state, showed a substantial efflux from the fetal hindlimb during the fasting period. The fetal arteriovenous concentration difference of the branched-chain amino acids (leucine, isoleucine, and valine) increased significantly during fasting. These observations are consistent with the hypothesis that the ovine fetus adapts to a diminished supply of glucose from the mother by enhanced amino acid catabolism and, possibly, proteolysis with subsequent release of gluconeogenic precursors in the form of alanine and glutamine.
Arachidonic acid mobilizes calcium and stimulates prolactin secretion from GH3 cells
Authors: Kolesnick R. N. , Musacchio I. , Thaw C. , Gershengorn M. C.
Published: December 2017

Because arachidonic acid and/or its metabolites may be intracellular effectors of calcium-mediated secretion, we studied whether arachidonic acid added exogenously mobilizes calcium and stimulates prolactin secretion from GH3 cells, cloned rat pituitary cells. Arachidonic acid caused efflux of 45Ca from preloaded cells and stimulated prolactin secretion. The concentration dependencies of these effects were similar; stimulation was attained with 3 microM arachidonic acid. To determine indirectly whether these effects may be caused by arachidonic acid itself, not via conversion to metabolites, two experimental approaches were used. First, inhibitors of arachidonic acid metabolism, eicosatetraynoic acid and indomethacin, did not inhibit arachidonic acid-induced prolactin secretion. And second, alpha-linolenic acid, which cannot be converted to arachidonic acid, and linoleic acid, but not saturated fatty acids of equal chain length, stimulated 45Ca efflux and prolactin secretion. These data demonstrate that arachidonic acid added exogenously causes Ca2+ mobilization and prolactin secretion from GH3 cells and suggest that arachidonic acid itself, not via metabolism, may be a cellular regulator of prolactin secretion.
Enhanced muscle glucose metabolism after exercise in the rat: the two phases
Authors: Garetto L. P. , Richter E. A. , Goodman M. N. , Ruderman N. B.
Published: December 2017

Thirty minutes after a treadmill run, glucose utilization and glycogen synthesis in perfused rat skeletal muscle are enhanced due to an increase in insulin sensitivity (Richter et al., J. Clin. Invest. 69: 785-793, 1982). The exercise used in these studies was of moderate intensity, and muscle glycogen was substantially repleted at the time (30 min postexercise) that glucose metabolism was examined. When rats were run at twice the previous rate (36 m/min), muscle glycogen was still substantially diminished 30 min after the run. At this time the previously noted increase in insulin sensitivity was still observed in perfused muscle; however, glucose utilization was also increased in the absence of added insulin (1.5 vs. 4.2 mumol X g-1 X h-1). In contrast 2.5 h after the run, muscle glycogen had returned to near preexercise values, and only the insulin-induced increase in glucose utilization was evident. The data suggest that the restoration of muscle glycogen after exercise occurs in two phases. In phase I, muscle glycogen is depleted and insulin-stimulated glucose utilization and glucose utilization in the absence of added insulin may both be enhanced. In phase II glycogen levels have returned to near base-line values and only the increase in insulin sensitivity persists. It is proposed that phase I corresponds to the period of rapid glycogen repletion that immediately follows exercise and phase II to the period of supercompensation.
Brain peptide regulation of adrenal epinephrine secretion
Authors: Brown M. R. , Fisher L. A.
Published: December 2017

The studies described in this paper support the hypothesis that specific brain peptides may act as neurochemical substrates for the differential patterns of sympathetic nervous system and adrenomedullary responses to various provocative stimuli. Different treatments, e.g., exposure to ether vapor or cold, hemorrhage or hypoglycemia, elicit stimulus-specific changes in plasma concentrations of epinephrine and norepinephrine. Likewise, several neuropeptides, e.g., bombesin, corticotropin-releasing factor, thyrotropin-releasing factor, and somatostatin-related peptides, act within the central nervous system to produce differential changes in the relative concentrations of epinephrine and norepinephrine in plasma. The possibility that these peptides may be involved in generating stimulus-specific changes in plasma catecholamine concentrations following various physiological and pharmacological treatments is discussed.
Humoral responses to intracerebroventricularly administered angiotensin II in dogs
Authors: Eguchi T. , Bravo E. L.
Published: December 2017

The mechanism(s) by which intracerebroventricularly administered angiotensin II (ANG II) regulates aldosterone production was investigated in dogs with chronically implanted cannula into a lateral cerebroventricle. In salt-replete and salt-depleted dogs, artificial cerebrospinal fluid (CSF) with or without ANG II (1, 10, 100 ng X kg-1 X min-1) was infused intracerebroventricularly for 2 h under pentobarbital anesthesia. Artificial CSF produced no significant humoral changes. Intracerebroventricular ANG II decreased plasma renin activity and increased both ACTH and plasma cortisol in both groups but decreased plasma aldosterone (PA) only in salt-depleted dogs. Dexamethasone pretreatment during intracerebroventricular ANG II decreased PA further in salt-replete but not in salt-depleted dogs. Moreover, the fall in PA during intracerebroventricular ANG II in salt-depleted dogs was prevented when intravenous infusion of ANG II (10 ng X kg-1 X min-1) was given simultaneously to maintain circulating ANG II levels. We conclude that PA response to intracerebroventricular ANG II is mediated primarily through the renin-angiotensin system in the salt-depleted state; however, in the salt-replete state, ACTH assumes a more important role.
Relationship between PG and beta-adrenergic pathways to renin release in rat renal cortical slices
Authors: Henrich W. L. , Campbell W. B.
Published: December 2017

The precise importance of prostaglandin (PG) in the beta-adrenergic pathway to renin release is unresolved. Thus, we examined this question using renal cortical slices from Sprague-Dawley rats incubated in Krebs-Ringer bicarbonate mixture (KRB), KRB + isoproterenol (10(-5) M, ISO), or a solution containing KRB + ISO + either propranolol (PRO, 10(-5) M) or indomethacin (IN, 10(-5) M). Media samples were assayed for renin activity, 6-keto-PGF1 alpha (the stable metabolite of PGI2), and PGE2. ISO only increased renin release 1.96-fold; modest increments in 6-keto-PGF1 alpha and PGE2 also occurred. The addition of PRO prevented these increases. In the next series of studies, ISO again increased renin, but the addition of IN failed to modify this increase in renin release. However, IN did prevent any increase in 6-keto-PGF1 alpha or PGE2. Meclofenemate (10(-5) M) provided results similar to those of IN. PGI2 was found to stimulate the release of renin in concentrations of 10(-7) M. The combination of submaximal stimulatory concentrations of PGI2 (10(-6) M, a 1.6-fold increment) and ISO (10(-6) M, a 1.7-fold increment) produced a synergistic increase in renin release (2.84-fold). These results demonstrate that renal prostaglandins do not function as essential mediators of the beta-adrenergic pathway to renin release. Rather, high concentrations of prostaglandins may increase the renin-releasing action of beta-agonists, thereby modulating the release of renin.
Transport of 125I-EGF into milk and effect of sialoadenectomy on milk EGF in mice
Authors: Gresik E. W. , van der Noen H. , Barka T.
Published: December 2017

Epidermal growth factor (EGF) (urogastrone) is found in high concentrations in mouse and human milk. The origin of milk EGF is unknown. Milk samples were collected from lactating mice 2-6 h after the intravenous administration of a tracer dose of 125I-labeled EGF. The milk contained relatively high levels of radioactivity of which 35–46% was precipitated by trichloroacetic acid-phosphotungstic acid (TCA-PTA) and 26% by a specific antimouse EGF antiserum. Part of the radioactivity in milk was eluted from a Bio-Gel P-10 column at the point at which pure standard 125I-EGF was eluted. These data indicate that the mammary gland of the lactating mouse is capable of sequestering and transporting 125I-EGF into milk. Administration of a thousand-fold excess of unlabeled EGF caused no reduction in TCA-PTA-precipitable radioactivity in milk samples of mice given 125I-EGF. When mice were given 10 micrograms of unlabeled EGF and milk was collected 4 h later, compared with controls the EGF level in milk was doubled. Administration of EGF had no effect on lactose and protein concentrations in the milk, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed no qualitative or quantitative changes in the major milk proteins. Milk collected from lactating mice that were sialoadenectomized 6 mo earlier contained about 50% less EGF compared with controls. After the administration of 125I-EGF high concentrations of radioactivity were also found in the mammary and submandibular glands and in the stomach. In the latter organs, however, 95–96% of the radioactivity was in the acid-soluble fraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Osmotic control of vasopressin with chronically altered volume states in anephric dogs
Authors: Quillen E. W. , Skelton M. M. , Rubin J. , Cowley A. W.
Published: December 2017

Continuous peritoneal dialysis has been used to maintain anephric dogs at chronically sustained low, normal, and high volume states in order to study the long-term interaction of volume and osmotic stimuli in the control of plasma vasopressin (PAVP). Bilaterally nephrectomized dogs were maintained for 1–3 mo with normal plasma sodium and potassium levels and blood urea nitrogen of 70.1 +/- 10.8 mg/dl. During the first month, the dogs were dialysized to each of the three volume states. After each volume state had been maintained for 7 days, an osmotic forcing with intravenous distilled H2O and hypertonic NaCl was performed in the conscious state to quantitate the relationship between plasma osmolality (Posm) and PAVP. During the osmotic forcings left atrial pressure (LAP) averaged -2.4 +/- 0.5, 2.6 +/- 0.8, and 11.9 +/- 1.1 cmH2O; mean arterial pressure averaged 113 +/- 11, 125 +/- 10, and 148 +/- 8 mmHg, both respective for the low, normal, and high volume states. The slope of the normovolemic Posm-PAVP relationship was determined to be 0.047 pg X ml-1 X mosmol-1 X kg-1, and neither the hypovolemic or hypervolemic relationships were significantly different. The results demonstrate two additional points that must be considered in the control of PAVP. First, the severely depressed sensitivity of osmotic PAVP control suggests that either the dialysis procedures or the absence of the kidneys suppressed or eliminated some factor normally important to the secretion of vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)
The human sympathochromaffin system
Authors: Shah S. D. , Tse T. F. , Clutter W. E. , Cryer P. E.
Published: December 2017

Hypoglycemia stimulates adrenomedullary epinephrine secretion; standing stimulates sympathetic neural norepinephrine release. In five bilaterally adrenalectomized persons plasma epinephrine, measured with a sensitive single-isotope derivative assay, rose from 15 +/- 2 to 35 +/- 7 pg/ml (P less than 0.02) during hypoglycemia but did not increase during standing. In contrast, plasma norepinephrine rose during standing but not during hypoglycemia. Thus, in humans 1) extra-adrenal epinephrine secretion is regulated and derived from innervated cells other than sympathetic postganglionic neurons; 2) because the plasma levels of epinephrine in adrenalectomized individuals even in response to the potent stimulus of hypoglycemia are below physiological thresholds, any biological actions of extra-adrenal epinephrine in adults must be paracrine rather than endocrine in nature; 3) hypoglycemia does not appear to stimulate the sympathetic nervous system. In view of these findings, we propose that extra-CNS catecholamine-producing tissues be termed the sympathochromaffin system consisting of two components: 1) the sympathetic nervous system that releases the neurotransmitter norepinephrine from its postganglionic neurons, and 2) the chromaffin tissues, including the adrenal medullae, that contain cells that secrete epinephrine, norepinephrine, or dopamine. The plasma epinephrine concentration is a valid measure of its chromaffin tissue (predominantly adrenomedullary) secretion, whereas the plasma norepinephrine concentration is an index of sympathetic neuronal activity under some but not all conditions.
Adrenocorticotropin response to graded blood loss in the cat
Authors: Bereiter D. A. , Zaid A. M. , Gann D. S.
Published: December 2017

To assess the early endocrine and physiological responses to rapid blood loss, adult cats anesthetized with chloralose-urethan sustained transient hemorrhage (H) of different magnitudes for a 3-min duration. The magnitude of H was expressed as a percentage of initial total blood volume after plasma volume determination by dye dilution or on a per unit body weight basis. Considerable variation in total blood volume was observed at all body weights (range, 44.5–80.2 mg/kg). Adrenocorticotropin (ACTH) in peripheral venous plasma was not significantly altered by 10% H but increased modestly after 20% H by 5 min (148 +/- 67 pg/ml) and rose promptly after 30% H by 2 min (541 +/- 155 pg/ml) with a peak at 5 min (579 +/- 171 pg/ml). Total change in ACTH during the 15-min sampling period was proportional to the magnitude of H (r = 0.730, P less than 0.001). Mean arterial pressure (MAP) decreased significantly to all magnitudes of H by 1 min with a graded recovery during the 3-min hypovolemic period that was well correlated (r = 0.602, P less than 0.005) with the percentage of blood volume removed. Mean plasma glucose concentration was not significantly changed by 10 or 20% H but increased after 30% H by 5 min (46.2 +/- 10.2 mg/dl). Total glucose change from prestimulus levels during the 15-min sampling period was correlated with the magnitude of H (r = 0.731, P less than 0.001). Plasma norepinephrine increased equally after 20 or 30% H or 10 ml/kg H but was not significantly elevated after 10% H.(ABSTRACT TRUNCATED AT 250 WORDS)
Dopamine 3-sulfate inhibits aldosterone secretion in cultured bovine adrenal cells
Authors: Racz K. , Buu N. T. , Kuchel O. , De Lean A.
Published: December 2017

It has been demonstrated that dopamine inhibits the aldosterone (Aldo) secretion in bovine adrenal cells in vitro. Because the majority of the total circulating dopamine (DA) in bovine plasma (72%) is present in sulfoconjugated form (6.8 +/- 3.4 pmol/ml) and free DA, DA sulfate, and phenolsulfotransferase (PST) activity can be found in the bovine adrenal cortex, we examined whether the inhibitory action of free DA on angiotensin II- (ANG II) stimulated Aldo secretion by cultured bovine adrenal cells can also be reproduced by sulfoconjugated DA analogues. Cells from the bovine adrenal glands cultured for 3 days before testing responded to 10(-8) M ANG II stimulation by a 10- to 12-fold increase in Aldo output. This stimulatory effect was partially inhibited by the addition of free DA and DA 3-sulfate, whereas DA 4-sulfate was inactive. Both free DA and DA 3-sulfate produced their maximal inhibitory effect at a concentration of 100 microM, with a decrease in Aldo secretion by 61% (free DA) and 44% (DA 3-sulfate). The slightly different inhibition curves for DA and for DA 3-sulfate on Aldo secretion cannot be explained by liberation of free DA through hydrolytic processes because less than 1% free DA was detected after the incubation of the cells with sulfoconjugated DA. These in vitro findings suggest that DA 3-sulfate may be effective in complementing the dopaminergic inhibition of Aldo secretion at the adrenal level.
Bioactive parathyroid hormone in canine progressive renal insufficiency
Authors: Grunbaum D. , Wexler M. , Antos M. , Gascon-Barre M. , Goltzman D.
Published: December 2017

Bioactive parathyroid hormone and hormonal actions were monitored as hyperparathyroidism evolved in a model of progressive canine renal failure. Circulating levels of bioactive and immunoreactive parathyroid hormone rose as renal insufficiency worsened, but elevations, especially in bioactivity, were most marked in the final stage of uremia. By gel filtration analysis, the major circulating bioactive moiety was similar to the major glandular form of parathyroid hormone, although a smaller-molecular-weight entity was seen in the final stage of renal failure. Renal phosphate threshold fell, urinary hydroxyproline corrected for glomerular filtration rose, and plasma 1,25-dihydroxyvitamin D fell but remained detectable, as renal function deteriorated. The results demonstrate a progressive rise in bioactive parathyroid hormone, show the appearance of a small-molecular-weight bioactive entity in severe renal disease, and correlate effects of the rising bioactive parathyroid hormone with changes in renal phosphate handling and with skeletal resorption.
Insulin stimulates granulosa cells: increased progesterone and cAMP production in vitro
Authors: Ciancio M. J. , LaBarbera A. R.
Published: December 2017

Granulosa cells (GC) harvested from large (6-12 mm) follicles of cycling pigs obtained at the abattoir were incubated in the absence or presence of insulin and/or human chorionic gonadotropin (hCG). The total accumulation of progesterone and cAMP in the tissue plus medium was quantified by radioimmunoassay of hexane extracts and trichloroacetic acid extracts, respectively, and was related to cellular DNA content. Insulin (1 microgram/ml) had little effect on progesterone accumulation by freshly harvested GC incubated for up to 26 h at 37 degrees C. After preincubation of GC for 16 h in the absence of hormones, insulin (650 ng/ml) only enhanced subsequent basal progesterone accumulation after an additional 22 h. However, preincubation of cells for 20 h in the presence of 1 microgram/ml of insulin increased subsequent progesterone accumulation in both the absence and the presence of hCG (50 ng/ml). The effect of a 20-h preincubation with insulin on subsequent progesterone accumulation was related to the insulin concentration. At a maximally effective concentration of 5 micrograms/ml during the preincubation period, insulin increased subsequent basal and hCG-stimulated progesterone accumulations more than twofold. The concentrations of insulin in the preincubation medium that produced half maximal stimulation (ED50) were 300 and 200 ng/ml for subsequent basal and hCG-stimulated progesterone accumulations, respectively. After correction for loss of insulin immunoreactivity in the incubation medium, the ED50 levels were 60 and 50 ng/ml, respectively. Insulin elevated hCG-stimulated progesterone accumulation over the entire range of hCG concentrations; the effect on hCG-stimulated cAMP production was evident only at higher hCG concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of hepatic triiodothyronine production in the streptozotocin-induced diabetic rat
Authors: Jennings A. S.
Published: December 2017

The effect of diabetes on 3,5,3'-triiodothyronine (T3) production was determined in the isolated perfused rat liver. Induction of diabetes with streptozotocin resulted in decreased serum thyroxine (T4) and T3 levels and a progressive decline in hepatic T3 production over 5 days. The decline in T3 production resulted from decreased conversion of T4 to T3, whereas T4 uptake was unchanged. Insulin administration restored serum T4 and T3, hepatic conversion of T4 to T3, and T3 production to normal levels. When serum T4 levels in diabetic rats were maintained by T4 administration, the conversion of T4 to T3 and T3 production returned to control levels. However, restoration of serum T4 levels in fasted rats failed to correct the decrease in hepatic T4 uptake or T3 production. Glucagon, at supraphysiological concentrations in vitro and in vivo, slightly decreased T4 uptake and T3 production without altering the conversion of T4 to T3. These data suggest that the fall in serum T4 levels observed in diabetic rats is important in mediating the decreased hepatic conversion of T4 to T3 and T3 production.
Testicular function and sexual activity in senescent mice
Authors: Chubb C. , Desjardins C.
Published: December 2017

The steroidogenic potentials of testes from 6-mo-old and approximately 28-mo-old CB6F1 mice were compared by measuring the secretion rate of 11 steroids produced by testes perfused in vitro. Testes from 6- and 28- to 30-mo-old mice secreted similar amounts of testosterone, but marked differences in the secretion of testosterone biosynthetic intermediates were discovered. Testes of old mice produced significantly more (P less than 0.01) delta 5-steroids than young male mouse testes. The presence or absence of sexual activity among old male mice was not correlated with changes in testicular steroidogenesis or plasma steroid levels. The results suggest that selected alterations in androgen biosynthesis occur during aging, but that the decline in reproductive performance among old mice is not attributable to deficits in testicular steroidogenesis. Rather, age-associated losses in sexual activity may be mediated by disturbances in the central nervous system.
Bacteremia-induced changes in pituitary hormone release and effect of naloxone
Authors: Leshin L. S. , Malven P. V.
Published: December 2017

Acute bacteremia in sheep caused a surge of plasma beta-endorphin/beta-lipotropin (beta-EP/beta-LPH) associated with shivering behavior, tachycardia, hyperthermia, hemoconcentration, and decreased respiration rate. The surge of plasma beta-EP/beta-LPH was immediately followed by increases (P less than 0.05) in plasma prolactin and growth hormone (GH) concentrations and a depression (P less than 0.05) of plasma luteinizing hormone. These changes in pituitary hormone release were consistent with opioid-induced changes described in the literature. To examine possible opioid mediation, naloxone (2.5 mg X kg-1 X h-1) was continuously infused intravenously from 3 h before to 3 h after induction of an E. coli bacteremia. With the exception of plasma GH, naloxone failed to alter any of the hormonal or clinical parameters associated with bacteremia. For plasma GH, naloxone delayed (P less than 0.01) the increase but did not attenuate its magnitude, suggesting that an opioid mechanism may influence the timing of the pituitary GH release resulting from bacteremia. In general, opioid mechanisms sensitive to the present dosage of naloxone do not appear to mediate bacteremia-induced changes in hormonal or clinical parameters.
Triiodothyronine increases splanchnic release and peripheral uptake of glucose in healthy humans
Authors: Bratusch-Marrain P. R. , Gasic S. , Waldhausl W. K.
Published: December 2017

To examine the effect of experimental hyperthyroidism induced by triiodothyronine (T3) administration on glucose utilization and glucose-stimulated insulin secretion, euglycemic insulin clamp studies (A), hyperglycemic clamp studies (B), and estimation of splanchnic glucose metabolism after an oral glucose load by means of the hepatic venous catheter technique (C) were performed in healthy volunteers whose serum T3 concentration had been increased from 1.1 +/- 0.02 (SE) to 3.5 +/- 0.2 ng/ml. At plasma insulin concentrations of 77 +/- 6 microU/ml and maintenance of euglycemia, insulin-mediated glucose metabolism (6.8 +/- 0.4 mg X kg-1 X min-1) was not significantly altered following T3 exposure (7.2 +/- 0.7) in study A. When plasma glucose was raised and maintained at 7 mmol/l above basal, glucose uptake (10.6 +/- 0.7 mg X kg-1 X min-1) was increased to 14.6 +/- 2.0 mg X kg-1 X min-1 (P less than 0.02) following T3 administration in study B. In study C, basal splanchnic glucose output (104 +/- 10 mg/min) was markedly augmented when preceded by T3 exposure (167 +/- 17 mg/min; P less than 0.005). After a 75-g glucose load, splanchnic glucose output was enhanced by T3 by 30% (43.4 +/- 2.2 vs. 56.9 +/- 6.6 g/150 min; P less than 0.05), whereas arterial plasma concentrations of glucose, insulin, and C-peptide were not significantly different. It is concluded that in healthy humans, exposure to elevated plasma concentrations of T3 increases the amount of glucose to be released from the splanchnic bed. Glucose tolerance, however, remains unaltered, because peripheral glucose uptake is increased at the same time.
Enhancement of adrenomedullary catecholamine release by adrenal cortex in fetus
Authors: Cheung C. Y.
Published: December 2017

Catecholamines (CA) release from ovine fetal adrenomedullary cells was greatly enhanced by coincubation with adrenocortical cells. Total CA release was significantly elevated at 2 and 6 h of preincubation by seven- and twofold, respectively. With continuous coincubation of the two cell types, the enhancement of release was found to occur as early as 30 min and maintained for at least 6 h. A similar enhancement effect was observed when adrenomedullary cells were incubated in adrenocortical cell incubation medium (ACM). The stimulation of release was demonstrated for each of the three CA: dopamine, norepinephrine, and epinephrine. The effect of adrenocortical cells differed from that of adrenal steroids, because cortisol selectively stimulated the release of epinephrine only by one- to threefold after a latency of 6 to 9 h, whereas dehydroepiandrosterone had no effect on the release of the three CA at any time tested. Finally, the CA stimulatory activity in ACM was acid and heat stable, not extractable by ether but inactivated by proteolytic digestion. These results suggest that the adrenal cortex of the near-term ovine fetus secretes a factor that stimulates the release and perhaps synthesis of CA from the adrenal medulla.
Protein turnover in heart and diaphragm of rat fetus
Authors: Johnson J. D. , Wetmore D. L.
Published: December 2017

Fractional rate constants for protein synthesis (KS) in fetal rat heart and diaphragm were determined by the constant infusion technique. Uniformly labeled [14C]tyrosine was infused at a constant rate into the maternal jugular vein of unanesthetized unrestrained pregnant rats for 6–10 h at days 19 and 21 of gestation and KS calculated from the protein-bound to tissue-free tyrosine specific radioactivity ratio and the rate constant for attainment of plateau tyrosine specific radioactivity in fetal plasma (lambda p). Rate constants for protein degradation (KD) were calculated by subtracting fractional growth rate (KG) from KS. In both tissues, protein accretion during the most rapid phase of growth (day 19) was accomplished by greater rates of synthesis and lower rates of degradation when compared with a time of lesser growth (day 21).
Effects of benzyl alcohol on PTH receptor-adenylate cyclase system of canine kidney
Authors: Martin K. J. , McConkey C. L. , Stokes T. J.
Published: December 2017

In many systems, perturbations of membrane architecture by changes of lipid and phospholipid composition have been shown to alter the activity of membrane-bound enzymes. The present studies examined the effect of benzyl alcohol, an agent that has been shown to increase membrane fluidity, on the parathyroid hormone (PTH)-sensitive adenylate cyclase system of canine kidney. Benzyl alcohol progressively increased basal adenylate cyclase activity up to fourfold and maximal enzyme activity in the presence of PTH, GTP, guanylimidodiphosphate, and sodium fluoride by four- to sixfold. In the presence of 20 mM Mn2+ (no Mg2+), conditions under which enzyme activity is devoid of influence of guanine nucleotides or hormones, benzyl alcohol was without effect. PTH binding was increased by 25% in the presence of benzyl alcohol without a change in binding affinity. Fluorescent polarization studies using diphenylhexatriene showed a decrease in fluorescence anisotropy in the presence of benzyl alcohol. The results suggest that benzyl alcohol facilitates the interaction of the components of the adenylate cyclase system, presumably by increasing membrane fluidity. Alterations of membrane fluidity may be a potent means of regulating hormone sensitive adenylate cyclase activity.
Net release or uptake of histidine and carnosine in kidney of dogs
Authors: Cianciaruso B. , Fukuda S. , Jones M. R. , Kopple J. D.
Published: December 2017

Previous studies are equivocal as to whether the dog kidney produces histidine. Because one possible source of renal histidine is carnosine (beta-alanyl-L-histidine), we investigated net renal production (release) or utilization (uptake) (Qmet) of histidine and carnosine in 19 female dogs after they were fed histidine-free (9 dogs) or histidine-containing diets (10 dogs). Diets were fed in short-(2-11 days) or long-term (52-57 days) studies. Dogs were infused with half-normal saline for 120 min followed by an infusion of half-normal saline containing carnosine, 50 mumol/min. Renal Qmet histidine, calculated from either plasma or whole blood values, was positive during infusion of half-normal saline. During carnosine infusion, Qmet histidine increased markedly, and there was net renal uptake of carnosine. The Qmet histidine and carnosine were not different in the dogs fed histidine-free vs. histidine-containing diets. Thus there is net renal release of histidine in female dogs that increases when carnosine is administered. Qmet histidine or carnosine do not change adaptively when dogs are fed histidine-free diets.
Cultured Sertoli cell-mediated FSH stimulatory effect on Leydig cell steroidogenesis
Authors: Benahmed M. , Reventos J. , Tabone E. , Saez J. M.
Published: December 2017

To determine the precise role of Sertoli cells in the stimulating effects of follicle stimulating hormone (FSH) on Leydig cell activity, porcine purified Leydig and Sertoli cells were cultured separately or together in a chemically defined medium in the absence or presence of porcine, FSH 50 ng/ml. Leydig cell activity was evaluated using two parameters: human chorionic gonadotropin (hCG) binding sites; and hCG-stimulated cAMP production and testosterone secretion. First, it was found that FSH increases Leydig cell activity in crude Leydig cell preparations (40–60% of Leydig cells), whereas it exerts no effect on purified Leydig cells (greater than 90% of Leydig cells). Second, FSH stimulates the activity of Leydig cells cocultured with Sertoli cells, whereas it remains without effect on purified Leydig cells cultured alone. This stimulating effect of FSH on Leydig cell activity is dependent on the Sertoli cell number in the coculture. These data 1) show that the stimulating effect of FSH on Leydig cell function is mediated by Sertoli cells and 2) support the concept of local control of Leydig cell function originating from Sertoli cells.
Enhanced intestinal insulinotropic effect in streptozotocin-diabetic rats
Authors: Ikeda T. , Mokuda O. , Kuno S. , Tokumori Y. , Tominaga M. , Mashiba H.
Published: December 2017

To study the intestinal insulinotropic effects in the diabetic state, an investigation was made into the release of insulin from isolated rat pancreas perfused with portal venous effluent (PVE) obtained from the isolated perfused intestine of streptozotocin-induced diabetic rats. Rat intestine was perfused with Krebs-Ringer bicarbonate medium for 1 h, and the PVE was collected from both untreated and glucose-treated intestines of control and diabetic rats. The PVE, after adjusting its glucose concentration to the desired level, was used as the perfusing medium for the pancreas of a different rat. Glucose concentration in the perfusion medium was maintained at 5.5 mM for 20 min and at 16.7 mM for the next 30 min. Insulin output from pancreas perfused with PVE from untreated intestine of diabetic rats (252 +/- 45 ng/30 min, mean +/- SD) was similar to that of controls (269 +/- 72 ng/30 min). Pancreatic insulin output with PVE from glucose-treated intestine of diabetic rats (579 +/- 100 ng/30 min) was significantly greater compared with either that using PVE from untreated intestine of diabetic rats (P less than 0.01) or that from glucose-treated intestine of control rats (368 +/- 57 ng/30 min) (P less than 0.02). These results indicate that the insulinotropic effect is markedly enhanced in streptozotocin-induced diabetic rats.
Glucose turnover during insulin-induced hypoglycemia in liver-denervated rats
Authors: Mikines K. J. , Sonne B. , Richter E. A. , Christensen N. J. , Galbo H.
Published: December 2017

The role of hepatic autonomic nerves in glucose production during hypoglycemia was studied. Selective, surgical denervation of the liver was performed in rats, which reduced hepatic norepinephrine concentrations by 96%. Hypoglycemia was induced by 250 mU of insulin intra-arterially in anesthetized as well as in chronically catheterized, awake rats. Half of the anesthetized denervated or sham-operated rats had previously been adrenodemedullated. Glucose turnover was measured by primed, constant intravenous infusion of [3-3H]glucose. Before as well as during hypoglycemia the arterial glucose concentration and rates of production and utilization of glucose were similar in denervated rats and control rats. Also hepatic glycogen depletion was similar in the groups. The lack of effect of denervation could not be ascribed to compensating changes in hormone or substrate levels. In adrenodemedullated rats lack of glucose recovery from hypoglycemia was accompanied by delayed normalization of glucose clearance. In fed rats, activity in hepatic autonomic nerves is not a primary mechanism increasing glucose production during acute hypoglycemia. Epinephrine enhances glucose recovery by decreasing glucose clearance rather than by increasing glucose production, at least when glucagon is present.
Effects of mineralocorticoids and glucocorticoids on compensatory adrenal growth in rats
Authors: Phillips R. , Crock C. , Funder J.
Published: December 2017

The rapid compensatory growth seen in the remaining adrenal gland of the rat after unilateral adrenalectomy appears to require a functioning neural arc between the adrenal glands and the hypothalamus, but the role of adrenal or pituitary hormones is unclear. We have examined the effect of several steroids on the compensatory adrenal growth (CAG). Female and male rats (average wt 140 g) were unilaterally adrenalectomized and treated with aldosterone (2.1 micrograms/day), corticosterone (B, 28 micrograms/day), dexamethasone (28 micrograms/day), 9 alpha-fluorocortisol (9 alpha FC, 28 micrograms/day), or deoxycorticosterone (DOC, 28 micrograms/day) by continuous infusion for 3 days and then killed. The growth in the remaining adrenal was compared both with sham-operated rats treated with steroid infusions and with noninfused controls. In rats of this size females have larger adrenals than males; untreated male rats have significantly heavier left than right adrenals. In male rats the extent of CAG after no treatment or treatment with aldosterone B, 9 alpha FC, or DOC depended on the size of the adrenal gland removed. In both male and female rats CAG was not significantly affected by aldosterone, in contrast with a recent report, nor by B, 9 alpha FC, or DOC; no significant CAG was seen after dexamethasone. Taken together, these results and previous reports suggest that neurally mediated activation of pituitary and/or local adrenal growth factors may be responsible for CAG.
Muscle alpha-aminoisobutyric acid transport after exercise: enhanced stimulation by insulin
Authors: Zorzano A. , Balon T. W. , Garetto L. P. , Goodman M. N. , Ruderman N. B.
Published: December 2017

After exercise the ability of insulin to stimulate glucose transport and glycogen synthesis in rat skeletal muscle is markedly enhanced (25). The present study was designed to determine whether prior exercise augments the stimulation of other processes by insulin and, if so, whether this can be attributed to an increase in insulin binding to its receptor. Toward this end rats were run on a treadmill for 45 min at moderate intensity and the uptake of alpha-aminoisobutyric acid (AIB) by muscle was then assessed using the isolated perfused hindquarter preparation. Approximately 30 min after the cessation of exercise, both the sensitivity and responsiveness of insulin-stimulated AIB uptake were significantly enhanced in the soleus and the red portion of the gastrocnemius. As previously shown for glucose transport and glycogen synthesis, only small effects were observed in the white portion of the gastrocnemius, which unlike the other muscles was not depleted of glycogen during the run. Insulin-stimulated glucose utilization was also enhanced in the incubated soleus muscle of exercised rats; however, insulin binding to the soleus was not altered. These studies indicate that the ability of insulin to stimulate processes other than glucose transport and glycogen synthesis is enhanced in skeletal muscle after exercise and that this is not due to an alteration in insulin binding. The changes in insulin-stimulated AIB uptake and glucose metabolism after exercise are the reverse of those found in denervated and immobilized muscle and in both situations insulin binding is not altered. This suggests that a common factor(s) modulates the increase in insulin effect after exercise and the insulin resistance of disuse.
Effect of thyroid hormone excess on action, secretion, and metabolism of insulin in humans
Authors: Dimitriadis G. , Baker B. , Marsh H. , Mandarino L. , Rizza R. , Bergman R. , Haymond M. , Gerich J.
Published: December 2017

To determine the effect of thyroid hormone excess on insulin secretion, metabolism and action in humans, we examined intravenous glucose tolerance, glucose-induced insulin secretion, insulin clearance, monocyte insulin receptor binding, and the dose-response characteristics for the effects of insulin on glucose production, uptake, oxidation, and nonoxidative disposal in 10 normal volunteers for 14 days before and after oral administration of triiodothyronine (T3) in doses that increased plasma T3 to levels observed in spontaneous thyrotoxicosis (P less than 0.001). After T3 postabsorptive plasma glucose (P less than 0.05) and insulin (P less than 0.05) both increased; intravenous glucose tolerance was unaffected, but plasma insulin responses were increased (P less than 0.01); basal glucose production, uptake, and oxidation all increased (all P less than 0.05), whereas nonoxidative glucose disposal was unaffected (P = NS); monocyte insulin receptor binding increased (P less than 0.01) due to increased receptor affinity (P less than 0.05); and receptor number was not significantly altered (P = NS). Insulin clearance was increased. Insulin-induced suppression of glucose production was impaired (Km 22 +/- 3 vs. 37 +/- 7 microU/ml, P less than 0.02); maximal insulin-induced glucose uptake (10.7 +/- 0.6 vs. 13.0 +/- 0.9 mg X kg-1 X min-1, P less than 0.001) and oxidation (3.41 +/- 0.30 vs. 5.34 +/- 0.59 mg X kg-1 X min-1, P less than 0.001) were increased without a significant change in Km. However, submaximal rates of nonoxidative glucose disposal and glucose uptake were inappropriately low for the increased insulin receptor binding.(ABSTRACT TRUNCATED AT 250 WORDS)