bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of renal and osseous binding of parathyroid hormone and hormonal fragments
Authors: Demay M. , Mitchell J. , Goltzman D.
Published: December 2017

We compared receptor binding and adenylate cyclase stimulation of intact bovine parathyroid hormone (bPTH)-(1-84) and the synthetic amino-terminal fragments, bPTH-(1-34) and rat PTH (rPTH)-(1-34). Radioligands for binding studies were prepared by the lactoperoxidase technique and purified by high-pressure liquid chromatography. In both canine renal membranes and cloned rat osteosarcoma cells the amino-terminal fragments bound to a single order of sites; the affinity of rPTH-(1-34) exceeded that of bPTH-(1-34), correlating with its higher potency in stimulating adenylate cyclase. In studies with oxidized bPTH-(1--84), the middle and carboxyl regions of intact PTH were found to bind to both tissues but with higher affinity to osteosarcoma cells than to renal membranes. Our results demonstrate that rPTH-(1--34) is the most favorable probe of amino-terminal PTH binding and the most potent of the PTH peptides in stimulating renal and osseous adenylate cyclase. The results also show that midregion and carboxyl determinants within intact PTH contribute to hormone binding, which does not correlate with adenylate cyclase activation and appears more significant for skeletal than for renal binding.
Nuclear RNA polymerase activity in tumor-host livers
Authors: Ternell M. , Lonnroth C. , Lundholm K.
Published: December 2017

This study has evaluated changes in RNA synthesis in livers under the distant influence of a malignant tumor. A transplantable-induced sarcoma (MCG 101), transplanted on inbred adult mice (C57BL/6J), was used. Activities of DNA-dependent RNA polymerase (EC 2.7.7.6) were measured in relation to RNA content and translational activity. Liver nuclei from freely fed sarcoma-bearing mice had increased RNA synthesis. As a consequence of this, RNA content per DNA was increased in liver tissue. This was independent of depressed food intake and malnutrition. Elevated RNA synthesis, proportional to the tumor burden was due to an increased proportion of chromatin-engaged RNA polymerase I and II activities. RNA polymerase III activity (template-engaged form) was unchanged when evaluated in isolated nuclei, but appeared to be increased in partially purified extracts of nuclei. RNA content in tumor-host liver was a composite of increased levels of rRNA and tRNA, whereas the levels of poly(A)+ mRNA could not be measured as increased. Overall translational activities in vitro of mRNA from liver tissue of tumor-bearing, pair-weighed, and freely fed tumor-free controls were qualitatively and quantitatively different. mRNA from tumor-bearing mice directed an increased synthesis, particularly of larger proteins (above 55,000 daltons) compared with control animals. The results support the conclusion that previous evidence of elevated net protein synthesis in tumor-host liver is accompanied by increased transcription of genes coding for RNA and also for some or several hepatic proteins.
Effect of malaria on rate of protein synthesis in individual tissues of rats
Authors: Fern E. B. , McNurlan M. A. , Garlick P. J.
Published: December 2017

The levels of total RNA and protein and the fractional rate of protein synthesis were measured in nine tissues of rats infected with malaria and compared with those of uninfected controls fed either ad libitum or the same amount of food as that eaten by the infected animals (pair fed). Apart from spleen there were no appreciable differences in any of the three aspects measured in the early part of the infection (on day 4). By day 10, however, some nonmuscle tissues from infected rats had increased amounts of RNA and protein relative to the ad libitum controls, whereas skeletal and smooth muscle both showed decreased levels. In most cases the content of RNA and protein were higher in tissues from infected rats when compared with the pair-fed controls. The rate of protein synthesis in spleen, lung, and heart of infected rats was higher or equal to that in ad libitum controls. In the other tissues it was lower. In many cases the observed changes in infected rats could not be attributed solely to a decreased food intake. The data illustrate how the response of protein metabolism to an infection differs in individual tissues, with some of them exhibiting catabolic responses and others anabolic ones.
Systemic lactate kinetics during graded exercise in man
Authors: Stanley W. C. , Gertz E. W. , Wisneski J. A. , Morris D. L. , Neese R. A. , Brooks G. A.
Published: December 2017

To investigate the relationships between oxygen consumption (VO2) and the rates of systemic lactate appearance (Ra) and disappearance (Rd), six healthy males were studied at rest and during continuous graded exercise using a primed continuous infusion of lactate tracer. Subjects exercised for 6 min at 300, 600, 900, and 1,200 kg . m . min-1. L-(+)-[1-14C]lactate was infused intravenously, and arterial samples were drawn at rest and every 2 min throughout the exercise period. Ra and Rd were calculated using nonsteady-state equations. At rest Ra and Rd were 14.4 +/- 1.8 and 15.1 +/- 2.2 mumol . kg-1 . min-1, respectively. Near steady-state values were observed toward the end of the first two work loads. Ra and Rd values were 32.8 +/- 2.3 and 37.4 +/- 1.3 mumol . kg-1 . min-1 during min 5 and 6 at 300 kg . m . min-1 and were 59.1 +/- 2.6 and 55.4 +/- 2.3 mumol . kg-1 . min-1 during min 5 and 6 at 600 kg . m . min-1. Ra was significantly greater than Rd at both 900 and 1,200 kg . m . min-1. Ra and Rd averaged 145.4 +/- 10.5 and 110.2 +/- 5.6 mumol . kg-1 . min-1, respectively, during the last 2 min at 900 kg . m . min-1, and 309.4 +/- 20.8 and 169.7 +/- 10.6 mumol . kg-1 . min-1, respectively, at 1,200 kg . m . min-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Interaction of prolactin with adrenal hormones in blood pressure regulation in rats
Authors: Mills D. E. , Woods R. B.
Published: December 2017

This study examined the role of the adrenals in the systolic blood pressure (BP) response to ovine prolactin (oPRL) administration as well as the interaction of oPRL with epinephrine (EPI), norepinephrine (NOR), and corticosterone (CORT) on BP in the rat. After intraperitoneal implantation of 7-day osmotic minipumps releasing 0.6 micrograms oPRL/h in 0.9% NaCl on day 1, BP was measured via tail cuff on days 1, 4, and 7 in adrenalectomized (ADX) and sham-ADX male rats (n = 8/group). BP was also measured in ADX rats receiving CORT (27.0 micrograms/h), EPI (1.7 micrograms/h), NOR (5.0 micrograms/h), CORT + oPRL, EPI + oPRL, and NOR + oPRL by osmotic pump (n = 8/group). All ADX rats not receiving CORT were given 1.0% NaCl replacement for drinking water. oPRL increased BP over 17 days in sham-ADX rats (P less than 0.01) but had no effect in ADX rats. BP also increased over 7 days in ADX animals receiving CORT, EPI (P less than 0.01), and NOR (P less than 0.01). BP responses to CORT + oPRL and EPI + oPRL were similar to those of CORT and EPI alone, respectively. However, the BP response to NOR + oPRL on day 4 was 250% (P less than 0.01) that to NOR alone and similar to NOR alone on day 7. Replacement of CORT + NOR + oPRL did not prolong the oPRL-induced sensitization to NOR. In no instance did oPRL, by itself, alter heart rate. These data suggest that the pressor response to oPRL requires the presence of the adrenal glands and that oPRL transiently potentiates the pressor response to NOR in vivo.
GnRH-stimulated LH release from rat anterior pituitary cells in culture: refractoriness and recovery
Authors: Jinnah H. A. , Conn P. M.
Published: December 2017

Previous reports have demonstrated that long-term continuous administration of gonadotropin-releasing hormone (GnRH) to pituitary cells results in a decreased level of gonadotropin secretion. The present report demonstrates that cultured rat anterior pituitary cells preincubated for 6 h in 10(-9) or 10(-7) M GnRH became refractory to further stimulation by the releasing hormone. Cells required 2-4 days to recover from the refractory condition. Cells also became refractory to GnRH when luteinizing hormone (LH) release was blocked by Ca2+ chelation. Drugs such as veratridine, ionophore A23187, or high K+, which stimulated LH release without GnRH receptor occupancy, were also capable of causing refractoriness to GnRH in long-term exposure. These data suggest that the refractory state observed after stimulation with GnRH is a result of the combined effects of a Ca2+-independent receptor-mediated mechanism for desensitization and some other postreceptor mechanism. Tunicamycin interfered with recovery, whereas cycloheximide did not. This evidence presents a potential role for protein glycosylation in the restoration of responsiveness. Phorbol myristate acetate did not cause subsequent refractoriness to GnRH, and dibutyryl adenosine 3',5'-cyclic monophosphate had no measurable effect on the rate of recovery.
Experimental chronic hypoxic neuropathy: relevance to diabetic neuropathy
Authors: Low P. A. , Schmelzer J. D. , Ward K. K. , Yao J. K.
Published: December 2017

The cardinal electrophysiological abnormalities in experimental diabetic (EDN) and experimental galactose (EGN) neuropathy, models in which endoneurial hypoxia has been demonstrated, are a slowing in nerve conduction velocity (NCV) and a resistance to ischemic conduction block (RICB). These electrophysiological abnormalities are also present in human diabetic neuropathy, where microangiopathy has been demonstrated to be more severe than in EDN so that endoneurial hypoxia is also likely to be present. We examined the effects of endoneurial hypoxia per se on normal nerves. In rats subjected to chronic hypoxia (10% O2) for up to 10 wk, the two electrophysiological abnormalities had developed by 4 wk and were very similar in degree to those seen in EDN and EGN. These abnormalities occurred in the absence of hyperglycemia, nerve sorbitol accumulation, or myoinositol reduction. Resting O2 consumption was reduced, the percent increase in nerve lactate under anoxic stress was increased, and nerve free sugars were normal. Hexokinase and phosphofructokinase activities were not altered substantially when studied under conditions of O2 excess. These findings indicate that hypoxia per se will cause conduction slowing and suggest that the hypoxic nerve develops RICB because of a reduced energy requirement and an increased efficiency of anaerobic glycolysis, but without major changes in the activity of its controlling glycolytic enzymes.
Effect and mechanism of vagal nerve stimulation on somatostatin secretion in dogs
Authors: Ahren B. , Paquette T. L. , Taborsky G. J.
Published: December 2017

To investigate the effect of vagal nerve stimulation on the release of pancreatic somatostatin, we electrically stimulated (10 Hz, 5 ms, 13.5 mA, and 10 min) the thoracic vagi just below the heart in halothane anesthetized dogs (n = 15). The stimulation increased the pancreatic output of somatostatinlike immunoreactivity (SLI) (delta = +248 +/- 81 fmol/min, P less than 0.005; base-line levels = 455 +/- 150 fmol/min). min). Arterial plasma SLI levels increased as well (delta = +16 +/- 3 fmol/ml, P less than 0.001; base-line levels = 65 +/- 3 fmol/ml), reflecting stimulation of extrapancreatic SLI secretion. Significant vagal activation was verified by a fivefold increase of pancreatic output of pancreatic polypeptide (PP) (delta = +31.4 +/- 5.9 ng/min, P less than 0.001; base-line levels = 7.8 +/- 0.9 ng/min). Atropine pretreatment (n = 6) inhibited partially both the PP response (delta = +7.9 +/- 3.8 ng/min after atropine) and the pancreatic SLI response (delta = +92 +/- 29 fmol/min) to vagal nerve stimulation. However, atropine pretreatment did not modify the arterial SLI response (delta = +20 +/- 7 fmol/ml). Hexamethonium pretreatment (n = 9) completely abolished all three responses. We conclude that 1) electrical stimulation of the vagus stimulates pancreatic SLI, extrapancreatic SLI, and PP release in vivo in the dog; 2) both muscarinic and nonmuscarinic mechanisms mediate the PP and pancreatic SLI responses; 3) a nonmuscarinic mechanism mediates the extrapancreatic SLI response; and 4) all three responses are mediated via ganglionic nicotinic receptors.
LPS-caused secretion of corticosterone is mediated by histamine through histidine decarboxylase
Authors: Suzuki S. , Nakano K.
Published: December 2017

Escherichia coli lipopolysaccharide (LPS) induced strong time- and dose-dependent secretion of corticosterone (CS) in C3H/HeN mice. In contrast, C3H/HeJ mice were very insensitive to LPS; 100,000 times more LPS was required with C3H/HeJ mice for producing a similar degree of CS secretion as that of C3H/HeN mice. However, C3H/HeJ mice could efficiently respond to other types of stressors, immobilization stress or injection of histamine, a possible mediator of LPS-induced CS secretion (28), leading to a striking increase in the serum levels of CS. Adoptive transfer of spleen cells from C3H/HeN mice converted x-irradiated C3H/HeJ mice to the donor phenotype. Injection of LPS produced a large increase in the activity of histidine decarboxylase (EC 4.1.1.22) in the spleen, lung, and liver of C3H/HeN mice, whereas C3H/HeJ mice were far less responsive. Transfer of spleen cells from the C3H/HeN mice made C3H/HeJ mice sensitive to LPS, leading to an increase in histidine decarboxylase activity in the spleen. There was a statistically significant relationship between the activity of splenic histidine decarboxylase and the serum levels of CS. These results suggest that the LPS-induced secretion of CS is mediated by histamine through induction of histidine decarboxylase in the spleen, lung, and liver. This may be significant in relation to the host-defense mechanism against endotoxemia.
Increased brown adipose tissue thermogenesis in obese (ob/ob) mice fed a palatable diet
Authors: Himms-Hagen J. , Hogan S. , Zaror-Behrens G.
Published: December 2017

Feeding female genetically obese (ob/ob) mice a palatable "cafeteria" diet results in increased sympathetic nervous system activity in brown adipose tissue and hypertrophy and increased thermogenesis of this tissue. There is an associated increase in the capacity of the ob/ob mouse to respond thermogenically to noradrenaline, prolongation of its survival in the cold, and an increase in body temperature at all times of day. Thus the cafeteria diet overcomes the usual refractoriness of brown adipose tissue of the ob/ob mouse to noradrenaline and to sympathetic stimulation, increases the low capacity for a thermogenic response to noradrenaline, almost normalizes resistance to cold, and increases the "set point" at which the ob/ob mouse regulates its body temperature. It is concluded that the repetitive sympathetic nervous stimulation engendered by the high-fat cafeteria diet has a trophic action on brown adipose tissue that improves its atrophied functional state and that the low sympathetic nervous system activity usually seen in brown adipose tissue of ob/ob mice eating chow under animal house conditions results in secondary atrophy of the tissue. The results point to a central location for the defect in the ob/ob mouse, perhaps in the control of the sympathetic nervous system in relation to diet availability and composition and to environmental temperature.
Long-term effects of hypothalamic paraventricular lesion on CRF content and stimulated ACTH secretion
Authors: Makara G. B. , Stark E. , Kapocs G. , Antoni F. A.
Published: December 2017

The effect of short-term (1 wk) and long-term (6 wk) lesion of the paraventricular nucleus (PVN) on the hypothalamopituitary-adrenal axis was studied. Six weeks after PVN lesion there was no change in resting morning plasma ACTH and corticosterone levels. The increase of plasma ACTH levels that occurs 8 days after adrenalectomy was inhibited 6 wk after placing a lesion in the PVN. In contrast, 6 wk after PVN lesion the plasma ACTH response measured 3 min after laparatomy and intestinal traction under ether anesthesia was not significantly different from that in the controls. The responsiveness to corticotropin-releasing factor (CRF)-41 of anterior pituitary segments incubated in vitro increased slightly at 6 wk after PVN lesion. The amount of CRF-41-like immunoreactive material in the stalk-median eminence decreased to approximately 14% of the control, while that in neural lobe failed to change. We suggest that the ACTH hypersecretion after adrenalectomy is driven predominantly by CRF-and/or AVP-producing neurons in and around the PVN, whereas other sources of CRF-41, increased pituitary sensitivity or other hypothalamic factors, may restore stress-induced ACTH release in the absence of the region of the PVN.
Removal of infused amino acids by splanchnic and leg tissues in humans
Authors: Gelfand R. A. , Glickman M. G. , Jacob R. , Sherwin R. S. , DeFronzo R. A.
Published: December 2017

To compare the contributions of splanchnic and skeletal muscle tissues to the disposal of intravenously administered amino acids, regional amino acid exchange was measured across the splanchnic bed and leg in 11 normal volunteers. Postabsorptively, net release of amino acids by leg (largely alanine and glutamine) was complemented by the net splanchnic uptake of amino acids. Amino acid infusion via peripheral vein (0.2 g X kg-1 X h-1) caused a doubling of plasma insulin and glucagon levels and a threefold rise in blood amino acid concentrations. Both splanchnic and leg tissues showed significant uptake of infused amino acids. Splanchnic tissues accounted for approximately 70% of the total body amino acid nitrogen disposal; splanchnic uptake was greatest for the glucogenic amino acids but also included significant quantities of branched-chain amino acids. In contrast, leg amino acid uptake was dominated by the branched-chain amino acids. Based on the measured leg balance, body skeletal muscle was estimated to remove approximately 25-30% of the total infused amino acid load and approximately 65-70% of the infused branched-chain amino acids. Amino acid infusion significantly stimulated both the leg efflux and the splanchnic uptake of glutamine (not contained in the infusate). We conclude that when amino acids are infused peripherally in normal humans, splanchnic viscera (liver and gut) are the major sites of amino acid disposal.
Circulating forms of somatostatinlike immunoreactivity in human plasma
Authors: Shoelson S. E. , Polonsky K. S. , Nakabayashi T. , Jaspan J. B. , Tager H. S.
Published: December 2017

Circulating forms of somatostatinlike immunoreactivity (SLI) in humans were characterized using several chromatographic techniques. After gelfiltration chromatography on Bio-Gel P-6 columns greater than 90% of circulating SLI was of high molecular weight (MW) and eluted in the void volume. When plasma samples were passed through protein A-Sepharose columns, more than 85% of the high MW SLI was removed, indicating that this form of plasma SLI is mainly due to cross-reacting immunoglobulins. Extraction of 10-ml plasma samples from normal subjects on octadecyl silyl silica cartridges eliminated the high MW material. In addition, this extraction technique concentrated the two lower MW forms of SLI, which coelute on gel filtration chromatography with somatostatin-28 (S-28) and the tetradecapeptide form of somatostatin (S-14), respectively. Extracted plasma SLI was further analyzed by high-pressure liquid chromatography (HPLC). The results confirmed the identity of S-28 and demonstrated that S-14 is converted, in part, to Des-Alasomatostatin (S-13) following secretion into the circulation. At least four forms of SLI are thus present in human plasma: cross-reacting immunoglobulins, S-28, S-14, and S-13. Concentrations of SLI forms in the plasma of normal controls and patients with renal failure or cirrhosis were measured to assess the role of circulating somatostatin in health and disease. High MW SLI was elevated above normal in the plasma of patients with cirrhosis, but was not significantly elevated in patients with chronic renal failure. On the other hand, concentrations of plasma S-28 and S-13/14 (total concentrations of S-13 plus S-14) were elevated in patients with either chronic renal failure or cirrhosis.
Metabolic effects of chronic infusions of epinephrine and norepinephrine in rats
Authors: Racotta R. , Ramirez-Altamirano L. , Velasco-Delgado E.
Published: December 2017

Chronic infusions of epinephrine, norepinephrine, or vehicle were performed in adult male rats by means of subcutaneous implanted osmotic minipumps (ALZET). The calculated dose was 180 ng/min during 7-8 days. Daily food intake and body weight were measured during this period and also 7 days before and 5 days after it. During the period of infusion, norepinephrine stopped body weight gain while epinephrine-infused rats gained weight at the same rate as controls. Once the infusion period was finished, epinephrine-infused rats gained more weight than controls, while norepinephrine-infused rats just returned to the slope of weight gain of the controls. In no group did food intake change. In a second experiment, similar infusions were carried out in other rats on the same schedule; body temperature, glycemia, and serum insulin and triiodothyronine were measured. Epinephrine infusion significantly elevated glycemia and triiodothyronine, whereas norepinephrine infusion increased temperature and serum insulin. The results obtained by chronic administration of the catecholamines support the concept of a disassociation of adrenomedullary and sympathetic nervous system metabolic effects.
Adaptive changes in insulin and glucagon secretion during cold acclimation in the rat
Authors: Edwards C. I. , Howland R. J.
Published: December 2017

Arginine-stimulated insulin and glucagon outputs from isolated perfused pancreata of warm-acclimated and 2-, 4-, and 6-wk cold-acclimated rats (4 degrees C) were determined to assess whether observed changes in these parameters were a result of cold exposure per se or a part of the adaptive process of cold acclimation. Progressive and sequential changes were seen in both insulin and glucagon outputs. At 2 wk cold acclimation, glucagon rose and insulin output tended to fall, at 4 wk, glucagon output remained elevated and insulin output was further reduced, and at 6 wk, glucagon output had returned to control levels, whereas insulin output was substantially further reduced. These changes resulted in reduction of the insulin-to-glucagon molar ratio of the total arginine-induced output from 7.27 +/- 1.76 (SE) in the warm acclimate to 2.31 +/- 0.79 (SE) at 2 wk, 1.42 +/- 0.29 (SE) at 4 wk, and 1.26 +/- 0.21 (SE) at 6 wk cold acclimation. The data do not provide in vitro support for the hypothesis that changes in pancreatic hormone secretion in vivo are a consequence of cold exposure and not cold acclimation.
Central vasopressin system mediation of acute pressor effect of gamma-MSH
Authors: Gruber K. A. , Eskridge S. L.
Published: December 2017

Intravenous (iv) administration of gamma-melanocyte-stimulating hormone (gamma-MSH) produces central sympathetically mediated pressor and cardioaccelerator effects and increases the activity of hypothalamic vasopressinergic neurons. The autonomic actions are similar to infusion of vasopressin (Vp) into the hindbrain of 4th ventricle (Ven). To ascertain whether activation of the central Vp system is the proximate cause of the pressor effects of gamma-MSH, we investigated the effects of gamma-MSH in rats pre- and postblockade of central nervous system Vp receptors and in rats with a hereditary lack of vasopressin (Brattleboro strain). Central Vp receptor blockade significantly reduced (80%) the pressor effects of iv gamma-MSH. As a control, iv administration of the antagonist, while effective in blocking the pressor effect of iv Vp, had no effect on the gamma-MSH pressor response. When compared with their genetic controls (Long-Evans strain), Brattleboro rats also had greater than 80% reduction in their pressor response to iv gamma-MSH. The results indicate that circulating gamma-MSH activates the central Vp system to produce its sympathoexcitatory pressor effects.
Rat visceral yolk sac: a target for parathyroid hormone action
Authors: Gugi B. , Silve C. , Garabedian M.
Published: December 2017

The stimulation of cAMP production by parathyroid hormone [human PTH-(1-34)] in fetal membranes was studied over the last 9 days of pregnancy in the rat. PTH significantly stimulated cAMP production in the placental and capsular parts of the visceral yolk sac at all days studied. In contrast PTH stimulated cAMP production in the amnion only at days 14 and 17 and had no effect in the maternal and fetal sides of the placenta nor in the parietal yolk sac before it degenerated (day 14). The biochemical characteristics of PTH-stimulated cAMP production in visceral yolk sac are similar to those reported in other systems: a) maximal stimulation was obtained with 1.2 X 10(-7) M hPTH-(1-34) and 50% stimulation achieved by 2-3 X 10(-8) M; and b) the antagonist [Nle8,Nle18,Tyr34] bovine PTH-(3-34) amide competitively inhibited the stimulation of cAMP production by hPTH-(1-34). These results strongly suggest that the rat visceral yolk sac is a target organ for PTH during the last 9 days of pregnancy.
In vivo pulsatility of pancreatic islet peptides
Authors: Jaspan J. B. , Lever E. , Polonsky K. S. , Van Cauter E.
Published: December 2017

In vivo oscillations of pancreatic peptides are recognized in primates. To determine whether such oscillations also occur in other mammalian species and to examine their underlying mechanisms, portal vein levels of insulin, C-peptide, glucagon, somatostatin, pancreatic polypeptide (PP), and glucose were measured simultaneously at 1- or 2-min intervals in nine conscious dogs. For comparison with primates, additional experiments were conducted in baboons and humans. Computer-assisted pulse identification for both raw and smoothed data was performed and spectral estimations calculated after detrending. Concomitance and comovement between the fluctuations of the various peptides and glucose were tested. Prominent pulses at 10- to 14-min intervals were detected most regularly for insulin and glucagon and were frequently reflected in PP and somatostatin levels. Corresponding relative increments in plasma concentration averaged 54% for insulin, 16% for glucagon, 25% for PP, and 24% for somatostatin. Insulin pulses were concomitant with glucagon pulses in 80% of the cases. Pulses of PP were less frequent, although consistently associated with insulin pulses. Somatostatin pulses were less consistently associated with those of other peptides. Peptide oscillations were unrelated to glucose changes. Spectral analysis confirmed these results with peaks in the 10- to 14-min range for all peptides but no significant periodicity for glucose. No consistent delays or advances between the oscillations of the various peptides could be demonstrated. It is speculated that oscillatory behavior in the pancreas may be related to a central pacemaker mechanism, which involves insulin tightly coupled to glucagon, entraining the fluctuations of PP, and, inconsistently, of somatostatin.
Insulin sensitivity in adipocytes from subjects with varying degrees of glucose tolerance
Authors: Foley J. E. , Thuillez P. , Lillioja S. , Zawadzki J. , Bogardus C.
Published: December 2017

Previous studies showed that the sensitivity of glucose transport to insulin is lower in adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus and impaired glucose tolerance compared with subjects with normal glucose tolerance. This study analyzed the relationship between insulin sensitivity of glucose transport and glycemia in a large group of nondiabetic-nonglucose-intolerant subjects with a wide range of glycemic response to oral glucose. Seventy-four Pima Indians with 2-h postglucose load glucoses between 77 and 197 mg/100 ml, fasting plasma glucoses between 76 and 108 mg/100 ml, and no postload glucoses less than 199 mg/100 ml were studied. Isolated adipocytes were prepared in vitro after an abdominal fat biopsy, ED50 of insulin for glucose transport was correlated with 2-h postload glucoses, but not between insulin binding per cell or per cell surface area or in ED50 of insulin for antilipolysis and 2-h postglucose load glucoses. Although only 17% of the variation in glucose tolerance could be explained by a change in the sensitivity of glucose transport to insulin, the data suggests that a postinsulin-binding defect in the coupling of insulin binding to glucose transport may be an early step in the development of insulin resistance in human adipocytes.
Variance weighting functions in radioimmunoassay calibration
Authors: Gettys T. W. , Burrows P. M. , Henricks D. M.
Published: December 2017

Software packages for radioimmunoassay calibration assume that expected counting rate is a function of ligand dose. Previous studies have indicated that variances of counting rate are also related to dose, but the structure of individual assays does not permit precise estimation of counting rate variances at individual doses. The method described here uses results from an accumulation of assays to characterize the relationship between mean and variance of counting rate, thus providing a variance weighting function for the calibration. Analysis of 140 cortisol assays, all with two replicates of each of 50 sources (9 standard doses, 3 quality control preps, and 38 unknowns), led to an asymmetric rising ogive relating variances to means of counting rates. A rectangular hyperbola provided an adequate characterization of this relationship in an accumulation of 21 testosterone assays. Relationships between mean and variance of counting rate in 19 growth hormone assays and 7 triiodothyronine assays were characterized by a straight line and a rising exponential curve, respectively. Calibration curves, such as the commonly adopted logistic ogive in relation to log dose, are fitted by weighted least squares to observed counts directly using empirical weights proportional to the reciprocal of estimated counting variance. The advantage of this method is that all observations contribute to the calibration in accordance with their merit.
Ovarian increase in kinin-generating capacity in PMSG/hCG-primed immature rat
Authors: Espey L. L. , Miller D. H. , Margolius H. S.
Published: December 2017

Ovarian kinin-generating capacity was determined during induced ovulation in immature Wistar rats. The onset of ovulation was monitored by counting the number of ova in the oviducts at 2-h intervals after the administration of human chorionic gonadotropin (hCG). Ova began to appear in significant numbers at 14 h after hCG, with an average of 7.6 +/- 2.3 ova/rat. By 16 h after hCG, the oviducts contained 32.7 +/- 4.1 ova/rat. The ovaries from each group of animals were homogenized in phosphate-buffered saline, and extracts of this tissue were incubated for 200 min to allow the generation of kinins from endogenous kininogen. The amount of kinin generated by this procedure was measured by radioimmunoassay. At 0 h (i.e., just before the administration of hCG), the ovaries contained 5.90 +/- 0.60 pg kinin/micrograms protein per 200 min in the ovarian extract. By 4 h after hCG, the kinins increased significantly (P less than 0.05) to 13.16 +/- 3.61 pg kinin/micrograms protein. The kinins progressively increased (P less than 0.001) to 67.88 +/- 23.26 pg kinin/micrograms protein by 16 h after hCG. Indomethacin and cycloheximide significantly inhibited both kinin-generating activity and ovulation. These data suggest that kinin-forming activity and kinins may have a role in the ovulatory process of mammals.
Brown fat nuclear triiodothyronine receptors in rats
Authors: Burgi U. , Burgi-Saville M. E.
Published: December 2017

Brown adipose tissue (BAT) thermogenesis is important in the adaptation of body energy expenditure to cold exposure, fasting, and overfeeding and in the pathogenesis of obesity. Thyroid hormones are required for the normal functioning of BAT. The mechanism of their effect on BAT, however, has not yet been elucidated. Since most thyroid hormone effects are mediated via the binding of T3 to nuclear receptors (NT3R) the present studies were performed to investigate whether BAT contained NT3R and whether these NT3R were affected by cold exposure, fasting, overfeeding, or hypo- or hyperthyroidism. Rat BAT was found to contain NT3R with a maximum binding capacity (MBC) of 0.28 ng T3/mg DNA and a dissociation constant (Kd) of 3.2 X 10(-10) M. These parameters were unaffected by any of the experimental conditions studied. A major alteration of BAT NT3R MBC or Kd is thus not a causal factor in the changes in BAT thermogenesis induced by the above experimental conditions. In contrast, 3-wk overfeeding increased (+48%) and fasting decreased (-29%) the MBC of hepatic NT3R. Overfeeding increased serum T3 (+110%), while fasting decreased it (-37%).
Plasma glucose concentration determines direct versus indirect liver glycogen synthesis
Authors: Lang C. H. , Bagby G. J. , Blakesley H. L. , Johnson J. L. , Spitzer J. J.
Published: December 2017

In the present study hepatic glycogenesis by the direct versus indirect pathway was determined as a function of the glucose infusion rate. Glycogen synthesis was examined in catheterized conscious rats that had been fasted 48 h before receiving a 3-h infusion (iv) of glucose. Glucose, containing tracer quantities of [U-14C]- and [6-3H]glucose, was infused at rates ranging from 0 to 230 mumol X min-1 X kg-1. Plasma concentrations of glucose, lactate, and insulin were positively correlated with the glucose infusion rate. Despite large changes in plasma glucose, lactate, and insulin concentrations, the rate of hepatic glycogen deposition (0.46 +/- 0.03 mumol X min-1 X g-1) did not vary significantly between glucose infusion rates of 20 and 230 mumol X min-1 X kg-1. However, the percent contribution of the direct pathway to glycogen repletion gradually increased from 13 +/- 2 to 74 +/- 4% in the lowest to the highest glucose infusion rates, with prevailing plasma glucose concentrations from 9.4 +/- 0.5 to 21.5 +/- 2.1 mM. Endogenous glucose production was depressed (by up to 40%), but not abolished by the glucose infusions. Only a small fraction (7-14%) of the infused glucose load was incorporated into liver glycogen via the direct pathway irrespective of the glucose infusion rate. Our data indicate that the relative contribution of the direct and indirect pathways of hepatic glycogen synthesis are dependent on the glucose load or plasma glucose concentration and emphasize the predominance of the indirect pathway of glycogenesis at plasma glucose concentrations normally observed after feeding.
Extremity amino acid metabolism during starvation and intravenous refeeding in humans
Authors: Albert J. D. , Legaspi A. , Horowitz G. D. , Tracey K. J. , Brennan M. F. , Lowry S. F.
Published: December 2017

This study was designed to evaluate peripheral tissue amino acid metabolism in normal subjects who underwent starvation followed by intravenous administration of a nutritional repletion regimen with varying nonprotein caloric sources. Extremity amino acid (AA), arteriovenous differences, and blood flow were measured across forearm and/or leg of 12 healthy male subjects. Plasma AA flux [(arterial concentration - venous concentration) X flow X (1 - hematocrit); ml X min-1 X 100 ml tissue-1] was determined postabsorptively (PA), after 10 days of starvation (ST) and on the 10th day of intravenous feeding (IVF). There was a significant (P less than 0.05) decrease in efflux of total amino acids during the starvation study (-345 +/- 74) compared with the PA study (-1,463 +/- 263). Peripheral tissue AA uptake increased significantly (P less than 0.05) after 10 days of IVF (+276 +/- 79) compared with both PA and ST studies. There were no significant differences in extremity AA flux between those subjects who received 100% dextrose and those receiving 50% dextrose-50% lipid as a nonprotein caloric source. Linear relationships of AA infusion rate (IR) to AA flux (r = 0.845, P less than 0.001) and AA IR to [AA]art IVF (r = 0.842, p less than 0.001) were observed during IVF. Results of this study suggest that extremity flux determinations during IVF cannot be interpreted without correction for AA availability as reflected by AA infusion rate.
Insulin and insulinlike growth factor receptors and responses in cultured human muscle cells
Authors: Shimizu M. , Webster C. , Morgan D. O. , Blau H. M. , Roth R. A.
Published: December 2017

Specific receptors for insulinlike growth factors I and II (IGF-I and IGF-II) were found on cultured human myoblasts and myotubes. In contrast, myotubes but not myoblasts specifically bound insulin and were stimulated by nanomolar concentrations of insulin to take up deoxyglucose. In addition, in myoblasts, physiological concentrations of IGF-I and -II and, to a lesser extent, insulin stimulated two- to threefold the uptake of the nonmetabolizable amino acid analogue methylaminoisobutyric acid (MAIB). In myotubes, uptake of MAIB was stimulated preferentially by IGF-I. Monoclonal antibodies that preferentially recognize either the insulin receptor or the IGF-I receptor were utilized to examine which receptors mediated the biological effects of these hormones. The effects of insulin on both myoblasts and myotubes appeared to be mediated in part by the insulin receptor and in part by the IGF-I receptor. In myotubes, the effects of IGF-I and -II both appeared to be mediated through the IGF-I receptor. In myoblasts, the effects of the two IGFs appeared to be in part mediated by the IGF-I receptor and in part mediated by either the IGF-II receptor or another type of IGF-I receptor. The present results suggest that cultured human muscle cells provide a useful model system in which to study the biological actions of insulin and the IGFs.
Secretion and degradation of insulin and glucagon in carbon tetrachloride-induced liver injury rats
Authors: Ikeda T. , Takeuchi T. , Ito Y. , Murakami I. , Mokuda O. , Tominaga M. , Mashiba H.
Published: December 2017

To elucidate the mechanism of hyperinsulinemia and hyperglucagonemia in liver diseases, secretion of insulin and glucagon from perfused pancreas and extraction of insulin and glucagon by perfused liver were investigated in carbon tetrachloride inhalated liver injury rats. Fasting plasma insulin and glucagon levels and insulin and glucagon levels after arginine injection (0.25 g/kg) in liver injury rats were significantly higher than those in control rats. Glucagon levels after glucose injection (0.5 g/kg) were slightly increased in the liver injury group. Insulin responses to 16.7 mM glucose and 10 mM arginine from perfused pancreas were similar in liver injury rats and control rats. Glucagon response to 10 mM arginine from perfused pancreas was also similar in liver injury rats and control rats. Insulin extraction by perfused liver in liver injury rats (45 +/- 9%) was significantly (P less than 0.05) lower than that (64 +/- 11%) in control rats, and glucagon extraction by perfused liver was also significantly (P less than 0.05) decreased in liver injury rats (57 +/- 8%) compared with controls (73 +/- 9%). It is concluded that in carbon tetrachloride-induced liver injury rats, hyperinsulinemia and hyperglucagonemia may be dependent on decreased insulin and glucagon extraction by the liver.
Specificity of effect of osmolality on aldosterone secretion
Authors: Taylor R. E. , Glass J. T. , Radke K. J. , Schneider E. G.
Published: December 2017

Small (3–7 mM) changes in [NaCl] have a marked inverse effect on angiotensin II- or K-stimulated aldosterone secretion by the isolated, perfused canine adrenal gland. The effect is due to the accompanying changes in osmolality rather than to the changes in [Na] or [Cl]. The present study was undertaken to determine whether osmolality is a specific and discrete signal that modulates the secretion of aldosterone only or is simply a nonspecific physical factor that alters the secretion of other adrenocortical hormones as well. The study also determined whether small changes in osmolality affect the conversion of corticosterone to aldosterone. The secretion of both cortisol and aldosterone by isolated canine adrenal glands responded in a dose-dependent fashion to adrenocorticotropin (ACTH), but in contrast to the rapid and potent modulating action of osmolality reported previously for angiotensin II- or K-stimulated aldosterone secretion, changes in osmolality at the midpoint of ACTH infusion had no detectable effect on either cortisol secretion or, unexpectedly, aldosterone secretion. This indicates that osmolality is a highly specific signal that modulates responsiveness of the zona glomerulosa to the factors, angiotensin II and K, which are considered to be most important in the acute regulation of aldosterone secretion, but does not influence secretion of cortisol by inner zones of the adrenal cortex. In glands treated with agents that block aldosterone production from endogenous precursors, small changes in osmolality had no detectable effect on the conversion of exogenous corticosterone to aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)
Non-steady-state measurement of glucose turnover in rats by using a one-compartment model
Authors: Proietto J. , Rohner-Jeanrenaud F. , Ionescu E. , Terrettaz J. , Sauter J. F. , Jeanrenaud B.
Published: December 2017

One of the tracer methods often employed to measure glucose turnover in the non-steady state uses the one compartment model of Steele (Ann. NY Acad Sci 1959). However, this model gives adequate results when it is assumed that only a fraction of the glucose pool takes part in rapid changes of glucose specific activity, thereby being necessary to use a correction factor called the “pool fraction.” The aim of this study was to experimentally determine the best pool fraction needed in the rat for the calculation of glucose turnover using a one-compartment model. This is important as no data are available so far in this widely used species. For this purpose, glucose turnover was measured in anesthetized lean and genetically obese fa/fa rats, using two different experimental designs. In all conditions, the error in estimating the total rate of glucose appearance was lowest when 0.5 was used as the pool fraction. The error was greater with an increase and a decrease in the pool fraction value. It is concluded that in the rat the one-compartment model measures changes in glucose turnover with reasonable accuracy in non-steady-state conditions and that a pool fraction of 0.5 gives the best results.
Secretory pattern of canine growth hormone
Authors: French M. B. , Vaitkus P. , Cukerman E. , Sirek A. , Sirek O. V.
Published: December 2017

Our aim was to define the secretory pattern of growth hormone (GH) under basal conditions in fasted, conscious, male dogs accustomed to handling. Blood samples were withdrawn from a cephalic vein at 15-min intervals. In this way, any ultradian rhythms, if present, could be detected within the frequency range of 0.042-2 cycles/h. In addition, samples were drawn at either 1- or 2.5-min intervals for 2.5 or 5 h to determine whether frequency components greater than 2 cycles/h were present. GH was measured by radioimmunoassay and the raw data were submitted to time series analysis employing power spectral estimation by means of fast Fourier transformation techniques. Peak plasma levels were up to 12 times higher than the baseline concentration of approximately 1 ng/ml. Spectral analysis revealed an endogenous frequency of 0.22 cycles/h, i.e., a periodicity of 4.5 h/cycle. The results indicate that under basal conditions the secretory bursts of canine GH are limited to one peak every 4.5 h.
Nuclear triiodothyronine receptor binding characteristics and occupancy in obese (ob/ob) mice
Authors: Hillgartner F. B. , Romsos D. R.
Published: December 2017

Obese (ob/ob) mice exhibit reduced adaptive thermogenesis associated with an impairment of thyroid hormone action. The mechanism underlying the latter defect was investigated by comparing the binding characteristics and occupancy of solubilized nuclear 3,5,3'-triiodothyronine (T3) receptors from livers of lean and obese mice. Scatchard analysis showed minimal differences in Bmax and Kd between phenotypes at both 4 and 8–10 wk of age, indicating that reduced hepatic thyroid hormone expression in obese mice is not caused by alterations in nuclear receptor concentration or affinity. In contrast, nuclear T3 receptor occupancy (endogenous T3 associated with the specific receptor divided by Bmax) was 14 and 23% lower in 4- and 8- to 10-wk-old obese mice, respectively. Together with reported changes in hepatic thyroid hormone-sensitive enzymes, these data are consistent with a diminished nuclear T3 signal initiating thyroid hormone action in obese mice. Decreased nuclear T3 receptor occupancy may be secondary to a low transport of plasma T3 to the nuclear pool. In conclusion, impaired hepatic thyroid hormone action in obese mice is mediated in part at least by a reduction in nuclear T3 receptor occupancy.
Effect of insulin and glucocorticoids on glucose transporters in rat adipocytes
Authors: Carter-Su C. , Okamoto K.
Published: December 2017

The ability of glucocorticoids to modify the effect of insulin on glucose transport was investigated in both intact isolated rat adipocytes and in membranes isolated from hormone-treated adipocytes. In intact adipocytes, dexamethasone, a potent synthetic glucocorticoid, inhibited insulin-stimulated 3-O-methylglucose transport at all concentrations of insulin tested (0-2,000 microU/ml). Insulin sensitivity, as well as the maximal response to insulin, was decreased by dexamethasone in the absence of a change in insulin binding. The inhibition was observed regardless of which hormone acted first, was blocked by actinomycin D, and resulted from a decrease in Vmax rather than an increase in Kt of transport. In plasma membranes isolated from insulin-treated adipocytes, glucose transport activity and the amount of glucose transporter covalently labeled with [3H]cytochalasin B were increased in parallel in a dose-dependent fashion. The amount of labeled transporter in a low-density microsomal fraction (LDMF) was decreased in a reciprocal fashion. In contrast, addition of dexamethasone to insulin-stimulated cells caused decreases in both transport activity and amount of labeled transporter in the plasma membranes. This was accompanied by a small increase in the amount of [3H]cytochalasin B incorporated into the glucose transporter in the LDMF. These results are consistent with both insulin and glucocorticoids altering the distribution of glucose transporters between the plasma membrane and LDMF, in opposite directions.
The cat: an animal model for studies of inactive renin
Authors: Glorioso N. , Troffa C. , Laragh J. H. , Atlas S. A. , Marion D. , Sealey J. E.
Published: December 2017

Inactive renin, prorenin, is found in high concentrations in human plasma. We report herein the characteristics of trypsin-activated inactive renin from cat kidney and plasma. Cat and human plasma inactive renin were activated by similar concentrations of trypsin. As in humans, there was more inactive than active renin in cat plasma; also, inactive renin was low but detectable after nephrectomy. Trypsin-activated renal inactive renin, purified on Cibacron blue agarose and pepstatin-amino-hexyl-Sepharose chromatography, was inhibited by pepstatin and by a renin inhibitor similarly to cat and human active renins. The pH optimum of cat renin was biphasic: the higher peak of active renin was at pH 5.7, whereas that of activated inactive renin was at pH 7.5. As in humans, active and inactive plasma renin increased during sodium depletion and inactive renin increased during beta-adrenergic blockade, while active renin decreased. These results demonstrate that cat inactive renin is similar to human prorenin. Therefore, the cat may be a useful model for the study of prorenin.