bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of NaCl on renin and aldosterone responses to potassium depletion
Authors: Kotchen T. A. , Guthrie G. P. , Galla J. H. , Luke R. G. , Welch W. J.
Published: December 2017

We have previously suggested that renin secretion is inversely related to the magnitude of absorptive chloride transport in the thick ascending limb of the loop of Henle. Potassium depletion inhibits chloride transport at this site in the nephron. Consequently, we studied the effects of varying sodium and chloride intakes on the renin and aldosterone responses to potassium depletion. Potassium depletion prevented suppression of plasma renin activity (PRA) by dietary NaCl loading and augmented the PRA response to NaCl deprivation. PRA was stimulated (P less than 0.01) by selective chloride (without sodium) deprivation, and potassium depletion did not augment this response. Potassium depletion did not interfere with suppression of PRA by albumin-induced volume expansion. Plasma aldosterone was suppressed by potassium depletion, and the effect of potassium depletion on aldosterone was augmented by NaCl deprivation. In conclusion, the magnitude of PRA stimulation and aldosterone suppression by potassium depletion is modulated by dietary NaCl intake. The results are consistent with the hypothesis that potassium depletion stimulates renin release by inhibiting chloride transport in the loop of Henle.
Metabolism of apoprotein B in cynomolgus monkey: evidence for independent production of low-density lipoprotein apoprotein B
Authors: Goldberg I. J. , Le N. A. , Ginsberg H. N. , Paterniti J. R. , Brown W. V.
Published: December 2017

The catabolism of very-low-density lipoprotein apoprotein B and its conversion to low-density lipoprotein was studied in five chow-fed cynomolgus monkeys following injection of radioiodinated homologous very-low-density lipoproteins. The mean (+/- SD) fractional catabolic rate of very-low-density lipoprotein apoprotein B was 0.97 +/- 0.20 h-1 and the mean (+/- SD) production rate was 0.76 +/- 0.20 mg X kg-1 X h-1. The percent of conversion of very-low-density lipoprotein apoprotein B to low-density lipoprotein ranged from 33 to 59%. In separate studies of low-density lipoprotein apoprotein B turnover performed using homologous radiolabeled low-density lipoprotein in five additional animals, the mean (+/- SD) fractional catabolic rate for low-density lipoprotein apoprotein B was 0.050 +/- 0.017 h-1 and the mean (+/- SD) apoprotein B production rate was 0.70 +/- 0.18 mg X kg-1 X h-1. Comparison of the total low-density lipoprotein apoprotein B production with that derived from very-low-density lipoprotein apoprotein B suggested that a large fraction of plasma low-density lipoprotein apoprotein B was derived from a source exclusive of circulating very-low-density lipoprotein apoprotein B. This was confirmed in two animals by simultaneous injection of radiolabeled very-low-density and low-density lipoproteins. Thus, a significant proportion of cynomolgus monkey low-density lipoproteins are produced either by direct hepatic secretion or by rapid conversion of lower-density lipoproteins before they appear in the peripheral circulation.
Insulin and gastric inhibitory polypeptide secretion in young milk-fed and adult goats
Authors: Nilssen K. J. , Hove K. , Jorde R.
Published: December 2017

Plasma concentrations of glucose, immunoreactive insulin (IRI), and immunoreactive gastric inhibitory polypeptide (IR-GIP) were studied in six adult and five young milk-fed goats after intravenous or intraduodenal infusions of glucose. Glucose concentrations after intraduodenal infusions were elevated from 3.5 to 4.7 mmol/liter on the average in adult and from 4 to 7 mmol/liter in young goats. Intravenous infusions were given at rates adjusted to mimic very closely the plasma glucose curves after intraduodenal infusions. Plasma IRI increased from 250 to 600 pmol/liter in adult and from 180 to 500-600 pmol/liter in young goats, but no significant differences were observed between intravenous and intraduodenal infusions. Duodenal infusions of glucose did not stimulate the release of IR-GIP in adult or young goats. It is concluded that the goat is lacking the incretin system for rapid disposal of oral glucose loads and that IR-GIP does not participate in regulation of glucose-stimulated insulin release in this species.
1- but not 24-hydroxylation of vitamin D is required for skeletal mineralization in rats
Authors: Brommage R. , Jarnagin K. , DeLuca H. F. , Yamada S. , Takayama H.
Published: December 2017

To evaluate the importance of 1- and 24-hydroxylation of 25-hydroxyvitamin D3 on skeletal mineralization, male and female rats from vitamin D-deficient mothers were administered from weaning either 100 pmol/day of 25-hydroxyvitamin D3, 50 pmol/day of 1,25-dihydroxyvitamin D3, or 100 pmol/day of 24,24-difluoro-25-hydroxyvitamin D3 as their sole source of vitamin D. A separate group of rats did not receive any vitamin D. 1,25-Dihydroxyvitamin D3 was given by constant infusion at a dose that normalized plasma calcium concentrations and produced normal body weight gains. Skeletal mineralization was studied by determining femur organic and ash weights. Femurs were obtained from male rats 6 wk after weaning, from female rats at conception, at the end of lactation, and 6 wk after lactation, and from weanling pups born to the female rats. No striking differences in femur organic and ash weights were found between 25-hydroxyvitamin D3 groups and either the 1,25-dihydroxyvitamin D3 group or the 24,24-difluoro-25-hydroxyvitamin D3 group, whereas the vitamin D-deficient rats had poorly mineralized femurs. These results indicate that 1,25-dihydroxyvitamin D3 at a lower dose is as fully active as 25-hydroxyvitamin D3 in promoting skeletal mineralization in the rat and that preventing the 24-hydroxylation of 25-hydroxyvitamin D3 by administering 24,24-difluoro-25-hydroxyvitamin D3 does not elicit any obvious skeletal abnormality, especially on mineralization.
Restraint-induced thermogenesis blunted by fasting in rats
Authors: Hayashi M.
Published: December 2017

Physical restraint was performed in fasted (F3, fasted for 3 days; F7, fasted for 7 days), and fed control (C) rats. In contrast to the C group, the F3 and F7 groups showed a low resting metabolism and a low calorigenic response to restraint. During restraint, plasma levels of norepinephrine (NE) and epinephrine (E) were markedly increased but were not significantly different between the C and F7 groups. Calorigenic responses to NE and E (6.0 and 12.0 nmol X kg-1 X min-1) were significantly less in the F3 and F7 groups than in the C group. Plasma concentrations of glucose were increased by the infusion of catecholamines in the C and F7 groups. The values were not different between the two groups. Plasma levels of free fatty acid in the F7 group were significantly higher than in the C group before and during catecholamine infusion. Plasma concentrations of thyroxine and triiodothyronine were significantly less in the F7 group than in the C group. The blunted restraint-induced thermogenesis in fasted rats may be mainly attributed to the decreased calorigenic response to catecholamines. The decreased calorigenic response may be due to suppressed utilization of energy substrates in calorigenic tissues produced by the lowered activity of thyroid hormone.
Pentose phosphate shunt, pyridine nucleotides, glutathione, and insulin secretion of fetal islets
Authors: Ammon H. P. , Bumiller G. , Duppenbecker H. , Heinze E. , Lutz S. , Verspohl E. J.
Published: December 2017

In rat fetal islets it was tested whether their failure to respond to glucose with insulin secretion might be due to inadequate changes of the redox state of pyridine nucleotides and of glutathione. In islets of newborn (5 days) and adult (3 mo) rats elevation of glucose produced an increase in insulin secretion, pentose phosphate shunt (PPS) activity, and NADPH/NADP, NADH/NAD, and GSH/GSSG ratios. An increase in the NADH/NAD ratio was also observed in islets of fetal rats, but in contrast to islets of newborns and adults no increase in insulin release, PPS activity, and the GSH/GSSG ratio was observed. However, at all glucose concentrations tested islets of fetal rats exhibited a high NADPH/NADP ratio similar to the ratio of adult rats in the presence of 16.7 mM glucose. It is suggested that in fetal islets there exists a lack of hydrogen transfer from NADPH to GSSG. The high NADPH/NADP ratio may in turn suppress PPS activity. It is possible that the missing insulin release of fetal islets in response to glucose is at least in part due to the fact that the oxidation-reduction state of the GSH/GSSG system also does not respond to the elevation of the glucose concentration.
Interrelationships between PGE1 and PGI2 binding and stimulation of adenylate cyclase
Authors: Garrity M. J. , Westcott K. R. , Eggerman T. L. , Andersen N. H. , Storm D. R. , Robertson R. P.
Published: December 2017

The effects of prostaglandin E1 (PGE1) and prostacyclin (PGI2) on hepatic adenylate cyclase were studied in plasma membranes isolated from Sprague-Dawley rat livers. Both PGE1 and PGI2 stimulated this enzyme complex to the same maximal levels and with approximately the same EC50 (10(-7) M). Maximally stimulating concentrations of PGE1 and PGI2 were examined alone and together; their effects were not additive, indicating that the same enzyme complex was shared. Although a receptor for PGE1 could be demonstrated with a dissociation constant of 1 X 10(-8) M, PGI2 was only 1/100 as effective in competing for PGE1 binding sites (KD, 1 X 10(-6) M), indicating that these two prostaglandins may act via separate membrane receptors. PGI2 is known to be unstable at neutral pH; however, we have determined its half-life during these assays by a sensitive bioassay and concluded that the degradation of PGI2 is not sufficient to account for its inability to dissociate [3H]PGE1 binding. Further evidence that PGI2 might act through a distinct receptor was found in animals whose PGE1 receptors were 40% downregulated with a corresponding 28% decrease in PGE1-sensitive adenylate cyclase activity. These membranes had no such decrease in PGI2-sensitive adenylate cyclase activity. We conclude that 1) hepatic adenylate cyclase is equally sensitive to PGE1 and PGI2; 2) the same adenylate cyclase complex responds to both prostaglandins; and 3) PGE1 and PGI2 interact with separate membrane receptors in rat liver.
Stimulation of pancreatic polypeptide secretion in the dog by hypoglycemic agent HB 699
Authors: Ribes G. , Trimble E. R. , Wollheim C. B. , Blayac J. P. , Loubatieres-Mariani M. M.
Published: December 2017

HB 699 is a hypoglycemic agent that has a structural similarity to glibenclamid but does not contain the sulfonylurea group. We have studied the effects of HB 699 and the sulfonylurea glipizide on pancreatic polypeptide (PP) and insulin secretion in the dog. Both HB 699 and glipizide stimulated insulin release and caused hypoglycemia in normal dogs. The secretion of PP was stimulated by HB 699 before the onset of hypoglycemia, whereas, following glipizide administration, PP secretion increased only after the onset of hypoglycemia. As expected, in alloxan-diabetic dogs neither substance affected plasma insulin or blood glucose levels. There was, however, a stimulation of PP secretion by HB 699 that was not observed with glipizide. It appears therefore that HB 699, in contrast to glipizide, stimulates PP secretion in the absence of any changes in circulating glucose and insulin concentrations. The direct action of HB 699 on the pancreas was shown by stimulation of insulin and PP secretion in the in vitro perfused uncinate process. In view of its direct pancreatic actions, HB 699 may prove a useful tool for further study of PP secretory mechanisms.
Endotoxin dose. I. Hemodynamic, metabolic, and lethal consequences in Yucatan minipigs
Authors: Hand M. S. , Fettman M. J. , Chandrasena L. G. , Cleek J. L. , Phillips R. W.
Published: December 2017

This study was performed in part to establish an endotoxin dosage in miniature swine that would yield reproducible cardiovascular and metabolic aberrations over a specific 6-h sampling period, minimizing lethality during that time. Five groups of three 6-mo-old Yucatan miniature pigs were surgically fitted with jugular vein and carotid artery catheters. One week later they were placed in slings and infused for 6 h with Difco 055:B5 endotoxin at dosages of 0, 2.5, 7.5, 15, and 25 micrograms X kg-1 X h-1. Significant (P less than or equal to 0.05) time-dose interactions were observed in mean arterial pressure, plasma glucose, serum potassium, blood lactate, pyruvate, bicarbonate, pH, PO2, PCO2, and urea nitrogen. Significant (P less than or equal to 0.05) differences were seen in lethality by 5 days postendotoxin: 0 = 0%, 2.5 = 0%, 7.5 = 33%, 15 = 67%, and 25 = 100% lethal. These animals exhibited a sensitive dose response to endotoxin, often at two- or threefold dose differences. The 15 and 25 micrograms X kg-1 X h-1 groups consistently demonstrated the most profound changes in the parameters measured.
Porcine granulosa cell desensitization: prolonged FSH-responsive cAMP production in vitro
Authors: LaBarbera A. R. , Fisher A. E.
Published: December 2017

Granulosa cells from small (1-2 mm) follicles of porcine ovaries produced cAMP in response to follicle-stimulating hormone (FSH); they produced little cAMP in response to human chorionic gonadotropin (hCG) or to cholera toxin. Production, estimated by quantification of total cAMP (medium + cells) by radioimmunoassay, appeared to be episodic in the absence or presence of the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine (MIX) and continued for at least 20 h. Results of dual incubation experiments with thorough washing of cells between incubations indicated that cells remained responsive to FSH, to hCG, and to cholera toxin after prior exposure to homologous stimulator. Preincubation of cells for 3 h in the absence of stimulator enhanced FSH responsiveness. In experiments with heterologous stimulators in two incubations, first, preincubation with FSH enhanced subsequent hCG and cholera toxin responsiveness; and second, preincubation with hCG or cholera toxin did not affect FSH responsiveness. Desensitization of FSH-activated adenylate cyclase was never greater than 35%; the degree of attenuation was dependent on FSH concentration and duration of exposure to FSH. Cells perifused with medium containing MIX and a maximally effective concentration of FSH for 5 h released cAMP continuously. In summary, the results indicated that porcine granulosa cells do not become unresponsive to FSH after prolonged exposure to FSH in vitro.
Insulin is a physiological inhibitor of urinary zinc excretion in anesthetized dogs
Authors: Vander A. J. , Victery W. , Germain C. , Holloway D.
Published: December 2017

Renal clearance experiments were performed on anesthetized dogs to determine the role of insulin in regulation of urinary zinc excretion. Intravenous infusion of somatostatin (2 micrograms/min) increased zinc excretion by approximately 100%, in association with 67% decreases in the plasma concentrations of both insulin and glucagon. Infusion of insulin (30 mU X kg-1 X min-1) along with the somatostatin maintained plasma insulin constant and completely eliminated the somatostatin-induced hyperzincuria; indeed, a small decrease in zinc excretion invariably occurred. Infusion of insulin alone (60 mU X kg-1 X min-1) decreased zinc excretion in five of six dogs. Plasma zinc concentration fell progressively, but to the same extent, throughout the experiment in all protocols. None of the hormonal infusions altered glomerular filtration rate, plasma concentrations of sodium, calcium, or magnesium or urinary excretion of these cations. We conclude that insulin, at physiological plasma concentrations, exerts an inhibitory effect on urinary zinc excretion.
Liver ornithine decarboxylase in pregnant rats fed two levels of casein
Authors: Hitier Y. , Champigny O. , Bourdel G.
Published: December 2017

Liver ornithine decarboxylase (ODC) and tyrosine aminotransferase (TAT) activities were assessed at 2200 h (prandial phase) and at 1000 h (postprandial phase) in virgin and in pregnant (day 13-20) rats fed on different levels of casein and carbohydrate. In virgin rats, ODC levels were higher at 2200 h after resumption of eating than at 1000 hours, the inductive effect being greater with the high-casein than with the low-casein diet. Rapid deinduction followed termination of eating, resulting in equally low enzyme levels at 1000 h with both diets. On the contrary, prandial and postprandial levels of TAT were always greater with the high-protein diet. In pregnant rats, there was a progressive stimulation of ODC that reached a maximum on day 19. However, the inductive capacity of the high-protein diet was lower than that of the low-casein diet. Prandial rest was not followed by enzyme deinduction at 1000 h. In contrast, TAT stimulation remained dependent on overall casein ingestion. At constant casein but restricted carbohydrate intake, pregnant females exhibited a reduction in ODC stimulation. Thus, whereas in virgin females proteins are determinant in the regulation of ODC, during pregnancy there determinant in the regulation of ODC, during pregnancy there is a shift toward modulation by carbohydrates. Levels of liver urea and ornithine were found to vary in inverse proportion with the magnitude of ODC stimulation.
Norepinephrine turnover in obese (ob/ob) mice: effects of age, fasting, and acute cold
Authors: Knehans A. W. , Romsos D. R.
Published: December 2017

The possibility that low sympathetic nervous system (SNS) activity in brown adipose tissue (BAT) of 8-wk-old obese (ob/ob) mice results from their gross obesity at that age was investigated. Norepinephrine (NE) turnover, an estimator of SNS activity, was measured in BAT and other organs of 2-wk-old preobese ob/ob mice, and at 4 and 8 wk of age. Rates of NE turnover were 36% slower in BAT of preobese ob/ob mice than in lean littermates and remained slow in their BAT at 4 (-66%) and 8 (-56%) wk of age. In heart, rates of NE turnover were 48% slower in preobese ob/ob mice than in lean littermates, but the difference diminished at 4 (-21%) and 8 (-16%) wk of age. Rates of NE turnover in white adipose tissue, liver, and pancreas of obese mice were generally comparable with rates in these organs of lean mice. Effects of fasting (24 h) and acute cold exposure (14 degrees C for 8 h) were also examined. In general, fasting lowered and cold exposure elevated NE turnover equally in obese and lean mice. Ob/ob mice housed at 23-25 degrees C exhibit low SNS activity in their BAT prior to the onset of gross obesity, even though SNS activity in their BAT responds normally to an acute cold stress. This low SNS activity probably contributes to their subsequent high efficiency of energy retention.
Steroid secretion by mouse testes perfused in vitro
Authors: Chubb C. , Desjardins C.
Published: December 2017

We determined the concentration of steroids in blood plasma of CBF1 male mice and the steroidogenic potential of the mouse testis. Steroid secretion rates are based on measuring selected C18, C19, and C21 steroids in the venous effluent of testes perfused with a defined medium containing luteinizing hormone. Steroids were isolated by thin-layer and/or column chromatography and quantified by radioimmunoassay. These include pregnenolone, 17 alpha-hydroxypregnenolone, dehydroepiandrosterone, androstenediol, progesterone, 17 alpha-hydroxyprogesterone, androstenedione, testosterone, dihydrotestosterone, 3 alpha-androstanediol, and 3 beta-androstanediol. Testosterone is the primary steroid secreted by mouse testes perfused in vitro and is the chief androgen present in blood plasma. Pregnenolone, an obligatory intermediate in steroid synthesis, is converted to testosterone via two separate steroidogenic pathways in approximately equal proportions. This is unlike other species in which testosterone biosynthesis proceeds preferentially via either the delta 4 or the delta 5 pathway. Our results, taken together, provide the first comprehensive assessment of Leydig cell steroidogenic activity in the mouse, demonstrate putative enzymatic pathways subserving androgen biosynthesis, and establish the predominant steroids in the peripheral circulation of adult mice.
Ontogeny of hepatic insulin and glucagon receptors and adenylate cyclase in rabbit
Authors: Ganguli S. , Sinha M. K. , Sterman B. , Harris P. , Sperling M. A.
Published: December 2017

In rabbit liver plasma membranes (LPM), specific binding of 125I-insulin rapidly increased in late gestation and peaked at birth, declining thereafter. In contrast, 125I-glucagon binding was lowest in late gestation, somewhat higher at birth, and increased by 48 h although only to 20-25% of adult. These changes in binding were due to changing numbers of receptors involving predominantly high affinity sites for insulin and low affinity sites for glucagon, with only minor changes in affinity. Despite measurable glucagon receptors by birth, fetal LPM produced no increment above basal in cAMP production with maximal doses of glucagon (10(-6) M), prostaglandin E1 (10(-4) M), or epinephrine (10(-4) M). Near birth only NaF (10 mM) produced a modest but significant increment in cAMP. By 2 h postbirth, all stimuli evoked significant increments in cAMP production that increased progressively but was still only 15-20% of adult at 48 h. Furthermore, although specific binding of cholera toxin was greater in fetal LPM (11 +/- 1 vs. 6 +/- 1%), cholera toxin-stimulated cAMP production increased by only 12-26% above basal in the fetus compared with 220% in adult. Markers of membrane purity including 5'-nucleotidase, phosphodiesterase, and insulin or glucagon degradation were not different in fetus and adult. We conclude that receptors and components of the adenylate cyclase complex mature independently; initial coupling occurs between the G/F regulatory protein and the catalytic unit (NaF but not hormonal activation) followed within hours of birth by coupling to the hormone receptor.
In vivo insulin sensitivity in the rat determined by euglycemic clamp
Authors: Kraegen E. W. , James D. E. , Bennett S. P. , Chisholm D. J.
Published: December 2017

Our aim was to develop the glucose clamp (GC) technique in the conscious rat for assessment of in vivo insulin sensitivity. A 2-h euglycemic GC could be performed in chronically cannulated rats using 625 microliter blood. Overnight-fasted rats were infused with porcine insulin (1.67 mU . kg-1 . h-1). Insulin levels of 41 +/- 2 (SE) mU/liter were produced in rats aged 91 +/- 4 days with a 60- to 120-min glucose infusion rate (GIR60-120) of 10.6 +/- 0.6 mg . kg-1 . min-1 (n = 9) during euglycemia. GIR60-120 was significantly (P less than 0.025) reduced in rats aged greater than 130 days (mean, 169 +/- 16 days) to 7.7 +/- 1.2 mg . kg-1 . min-1 (n = 7). Metabolic clearance rate of porcine insulin (46 +/- 3 ml . kg-1 . min-1) and GIR60-120 compared with plateau plasma insulin levels are higher than values reported in humans. The latter may be due to suppression of a higher basal hepatic glucose production or increased potency of porcine compared with native insulin. We conclude that the GC can be accomplished in the rat. When combined with tracer administration and subsequent killing, it should provide a quantitative in vivo measurement of insulin sensitivity in individual tissues.
Impairment by aminooxyacetate of ionic response to nutrients in pancreatic islets
Authors: Lebrun P. , Malaisse W. J. , Herchuelz A.
Published: December 2017

Aminooxyacetate, an inhibitor of transamination reactions, was recently reported to prevent the induction of a more reduced state in the cytosolic redox couple, as normally evoked by glucose or 2-ketoisocaproate in rat pancreatic islets. The cationic effects of aminooxyacetate were examined, therefore, in perifused islets prelabeled with either 86Rb or 45Ca. Aminooxyacetate augmented the outflow of 86Rb from the islets whether in the absence or presence of an exogenous nutrient and slightly impaired the capacity of nutrients, especially 2-ketoisocaproate, to decrease 86Rb outflow. Aminooxyacetate abolished the nutrient-induced rise in 45Ca efflux that normally results from the stimulation by glucose or 2-ketoisocaproate of 40Ca influx into the islet cells. Aminooxyacetate, however, failed to suppress the early inhibitory effect of nutrients on 45Ca efflux. The alteration by aminooxyacetate of the cationic response to nutrient secretagogues coincided with a suppression of insulin release, whereas the cationic response to a nonnutrient stimulation by a high concentration of extracellular K+ was unaffected by aminooxyacetate. These findings suggest that the induction of a more reduced cytosolic redox state represents an essential link between metabolic events and both the decrease in K+ conductance and stimulation of Ca2+ inflow in the process of nutrient-induced insulin release.
Effects of severe long-term food deprivation and refeeding on adipose tissue cells in the rat
Authors: Miller W. H. , Faust I. M. , Goldberger A. C. , Hirsch J.
Published: December 2017

To determine whether it is possible to use diet to cause a loss of adipocytes, adipose tissue cellularity was examined in adult male rats subjected to unusually prolonged semistarvation. After 1 wk of total fast, rats were given a nutritionally inadequate glucose-electrolyte diet for up to 7 wk. This caused a 49% reduction of body weight, up to a 99% reduction in the weight of adipose tissue, and significant losses of total adipose tissue DNA content. Nevertheless, there was no evidence that fat cells had been lost. The number of fat cells in the right epididymal depots of the food-deprived rats equaled both the number seen in left depots after refeeding and the number seen in corresponding depots of nonfasted controls. Adipose tissue DNA synthesis, which declined 88% below control values during fasting, did increase as much as 2,000% above control values during refeeding. However, autoradiographs showed that the increase reflects only the replacement of lost endothelial and nonadipocyte mesenchymal cells; no labeled fat cell nuclei were found. Thus, severe, long-term food deprivation followed by refeeding causes loss and recovery of stromal-vascular cells in adipose tissue but no loss of fat cells.
Pituitary nuclear triiodothyronine receptors during development in the rat
Authors: Coulombe P. , Ruel J. , Faure R. , Dussault J. H.
Published: December 2017

Studies were undertaken to measure the pituitary nuclear triiodothyronine (T3) binding capacity (BC) during development in the rat. BC was measured in 0.4 M NaCl-solubilized receptors in 5-, 14-, 20-, 27-, 30-, 40-, 50-day-old rats and in adult animals. Results indicate that BC is lower in 5-day-old rats than in adult animals (0.397 +/- 0.02 vs. 0.797 +/- 0.06 pmol T3/mg protein) (mean +/- SE) (P less than 0.01). Hypothyroidism, induced during the neonatal period or in the adult animal, results in a significant decrease in BC (P less than 0.01) when compared with control rats. However, treatment of hypothyroid animals with T3 (0.4 micrograms/100 g body wt) for a period of 7-14 days significantly increased BC as compared with hypothyroid rats without apparent changes in Ka. The relative affinities of various thyroid hormone analogues for the nuclear receptor were also measured in the adult animal. The affinities of these analogues are in the following order: TRIAC greater than L-T3 greater than D-T3 greater than L-T4 greater than D-T4 greater than DIMIT greater than L-T2 greater than rT3. The present findings demonstrate the presence of high affinity nuclear T3 binding sites in the pituitary of neonatal rat and could thus account for the effects of thyroid hormones on GH synthesis and TSH secretion observed in these animals.
Predominance of renal and absence of hepatic metabolism of pancreatic polypeptide in the dog
Authors: Hagopian W. , Lever E. G. , Cohen D. , Emmanouel D. , Polonsky K. S. , Pugh W. , Moossa A. , Jaspan J. B.
Published: December 2017

Pancreatic polypeptide (PP) metabolism was studied in the dog. Metabolic clearance rate (MCR) of PP was found to be 9.5 +/- 0.9 ml . kg-1 . min-1, accounted for predominantly by renal extraction (34.9 +/- 2.6% of exogenous PP), which comprised 45.5 +/- 5.8% of total PP clearance. Hepatic extraction of both endogenous (-9.9 +/- 6.1%) and exogenous (2.2 +/- 1.4%) PP infused to pharmacological levels was negligible, as was its splanchnic extraction (4.2 +/- 0.9%). Renal organ clearance of exogenous PP (3.7 +/- 0.3 ml . kg-1 . min-1) closely approximated that of inulin (3.6 +/- 0.3 ml . kg-1 . min-1), indicating that renal PP metabolism occurs entirely by glomerular filtration without contribution from peritubular uptake mechanisms. Urinary PP, chromatographically indistinguishable from that in plasma but quantitatively accounting for less than 1% of overall renal PP uptake, indicated virtually complete renal degradation of the peptide to nonimmunoreactive fragments. Renal PP extraction was shown to be nonsaturable. Plasma half disappearance time of PP was 10.1 +/- 1.0 min and apparent distribution space 307 +/- 39 ml/kg. Linkage between the hepatic action and degradation of insulin and glucagon has been proposed, and in this light absent hepatic PP extraction is noteworthy. This finding, reminiscent of the hepatic handling of metabolically inert C-peptide and biologically inactive glucagon peptides, is consistent with the absence of demonstrable physiological function of PP.
Plasma clearance, transfer, and distribution of vitamin D3 from intestinal lymph
Authors: Dueland S. , Helgerud P. , Pedersen J. I. , Berg T. , Drevon C. A.
Published: December 2017

The clearance of vitamin D3 from plasma after intravenous injection to rats of intestinal lymph labeled in vivo with radioactive vitamin D3 has been studied. The half-life of the injected vitamin D3 was about 6 min. In double-label experiments the half-life was the same for vitamin D3 as for vitamin A, which is removed from the circulation as chylomicron remnants. Fractionation of the blood plasma according to the density showed that 2 min after the injection of the lymph 30-95% of the radioactive vitamin D3 was recovered in plasma fractions with higher densities than chylomicron remnants (d greater than 1.019 g/ml). The percentage of vitamin D3 in the chylomicron fraction (d less than 1.006 g/ml) of the injected lymph was 66-95%. Taking this into account it could be calculated that the amount of radioactive vitamin D3 transferred from chylomicrons or chylomicron remnants to plasma with d greater than 1.019 g/ml within 2 min varied from 26 to 72%. The transferred radioactivity was recovered in a protein fraction with chromatographic mobilities identical to the binding protein for vitamin D and its metabolites. During the first 13 min after injection the amount of radioactivity recovered in the liver was less than 10%, but from 15 to 55 min the amount increased to about 50% of the injected dose. These findings suggest that the transfer of vitamin D3 from chylomicrons to the alpha-globulin fraction previously observed in vitro is of importance for the in vivo handling of vitamin D3.(ABSTRACT TRUNCATED AT 250 WORDS)
L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase
Authors: Knudsen P. , Kofod H. , Lernmark A. , Hedeskov C. J.
Published: December 2017

Column perifusion of collagenase-isolated mouse pancreatic islets was used to study the dynamics of insulin release in experiments lasting for several hours. The methyl esters of L-leucine and L-arginine were synthesized. Whereas L-arginine methyl ester (L-arginine OMe) had no effect, L-leucine OMe stimulated the release of insulin. The effect of L-leucine OMe was maximal at 5 mmol/liter. Whereas the Km for glucose-stimulated insulin release was unaffected by 1 mmol/liter L-leucine OMe, the maximal release of D-glucose was increased by the amino acid derivative that appeared more effective than L-leucine. L-Leucine OMe was also a potent stimulus of insulin release from the perfused mouse pancreas. In the presence of 10 mmol/liter L-glutamine, 1 mmol/liter L-leucine OMe induced a 50- to 75-fold increase in insulin release. A similar stimulatory effect was also observed in column-perifused RIN 5F cells, a cloned rat islet tumor cell line. A twofold increase in islet glutamate dehydrogenase activity was induced by 5 mmol/liter L-leucine OMe, a larger effect than that of L-leucine (P less than 0.02), whereas L-arginine OMe had a small inhibitory effect. We conclude that L-leucine OMe is a potent stimulus of insulin secretion and that its effect on the beta-cells may be exerted by activating islet glutamate dehydrogenase.
Altered regulation of cardiac glycogen metabolism in spontaneously diabetic rats
Authors: Miller T. B.
Published: December 2017

Isolated perfused hearts from control Bio-Breeding/Worcester (BB/W) rats and spontaneously diabetic BB/W rats were studied to determine whether metabolic abnormalities that are expressed in alloxan-diabetic rats in the regulation of enzymes involved in glycogen metabolism could be observed in this non-chemically induced insulin-deficient rat. Perfusion of hearts from control rats with 10(-8) M insulin for 10 min resulted in activation of glycogen synthase (30% synthase I without insulin to 44% synthase I with insulin). Perfusion of hearts from BB/W diabetic rats demonstrated a lack of acute synthase activation with insulin and a 45% decrease in synthase phosphatase activity. Perfusion of hearts from BB/W diabetic rats with 0.28 microM epinephrine for 1 min resulted in a greater activation of phosphorylase (44% phosphorylase a) than that observed in BB/W control hearts (31% phosphorylase a) perfused under the same conditions. Epinephrine produced similar changes in cyclic AMP accumulation, protein kinase activation, and phosphorylase kinase activation in perfused hearts of BB/W control and diabetic rats. Further, phosphorylase phosphatase activities were not changed by epinephrine or insulin deficiency. These studies further document metabolic abnormalities in the BB/W diabetic rat that are attributable to insulin deficiency in a non-chemically induced model for insulin-dependent diabetes.
Role of hexose monophosphate shunt in parathyroid hormone secretion
Authors: Morrissey J. J. , Klahr S.
Published: December 2017

The metabolism of labeled glucose by collagenase-dispersed bovine parathyroid cells was examined. When the medium calcium ion concentration was increased to 2.0 mM, the rate of 14CO2 release from [1-14C]glucose was increased 169 +/- 45% compared with the rate of 0.5 mM calcium. There was no significant change in the rate of 14CO2 release from [6-14C]glucose by this maneuver. The greatest increase in 14CO2 release and decrease in parathyroid hormone secretion occurred between medium calcium ion concentrations of 0.5-1.5 mM. This difference in the metabolism of glucose represents a true increase in hexose shunt activity because the incorporation of label from either [1-14C]- or [6-14C]glucose into parathyroid tissue lipids was equal. This suggests equilibration of label at the level of triose-phosphates. The increase in hexose shunt activity was not due to a calcium-mediated increase in glucose uptake because calcium changes did not affect 2-[3H]deoxyglucose transport by the cells. Phenazine methosulfate added to cells incubated at 0.5 mM calcium selectively increased hexose shunt activity in a dose-dependent manner (91 +/- 33% overall) and concomitantly inhibited parathyroid hormone secretion 65% overall at 0.5 mM calcium. The compound 6-aminonicotinamide inhibited hexose shunt activity but could not overcome the inhibition of hormone secretion at 2.0 mM calcium. A decrease in protein biosynthesis cannot fully explain the inhibition of hormone secretion by calcium or phenazine methosulfate because [3H]-leucine incorporation into total cell protein was not as affected as secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Vasopressin, ACTH, and blood pressure during hypoxia induced at different rates
Authors: Raff H. , Shinsako J. , Keil L. C. , Dallman M. F.
Published: December 2017

We decreased arterial PO2 at three different rates and measured blood pressure (BP), vasopressin (AVP), ACTH, and corticosteroid levels in nonsurgically stressed, anesthetized, paralyzed dogs. PaO2 was lowered to 28 Torr in 2 (fast), 10 (moderate), and 20 min (slow). The fast dPO2/dt produced a large spike in BP. Increases in AVP, ACTH, and corticosteroids were similar regardless of the dPO2/dt. When the spike in BP during the fast dPO2/dt was prevented with nitroprusside, hormone levels increased more quickly and were higher during the first 20-30 min of hypoxia. By 60 min, hormone levels were not different between experiments. The data suggest that 1) faster decreases in PO2 produce larger increases in BP, 2) increases in AVP, ACTH, and corticosteroids are primarily sensitive to the level of steady-state PaO2, and 3) increases in BP inhibit stress-induced increases in AVP and ACTH.
Interaction of atropine with naloxone to alter anterior pituitary hormone secretion
Authors: Huang X. Y. , McCann S. M.
Published: December 2017

The effects of third ventricular injection of naloxone and atropine, alone and together, on plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), growth hormone (GH), and thyroid-stimulating hormone (TSH) were studied in conscious, ovariectomized (OVX) rats. Samples were removed from unrestrained rats that had been previously implanted with an atrial cannula, and plasma hormone levels were determined by radioimmunoassay. Intraventricular injection of naloxone (30 micrograms) induced increases in plasma LH and GH concentrations, decreased plasma PRL levels, but did not alter plasma TSH. When atropine (100 micrograms) was injected intraventricularly, there was a decrease in plasma LH and an increase in PRL levels but no alterations in the levels of the other hormones. The action of naloxone on PRL and GH release was eliminated by simultaneous administration of atropine, but there was only a slight reduction in its effect on LH. The results indicate that central cholinergic neurons may play an important role, via muscarinic type receptors, in mediation of the effects of naloxone and presumably opiates on PRL and GH release, whereas the effects on LH appear to proceed independently of cholinergic neurons.
Suppression of renin secretion by insulin: dependence on extracellular calcium
Authors: Cohen A. J. , Laurens P. , Fray J. C.
Published: December 2017

The isolated perfused rat kidney was used to examine the effect of insulin on renin release (RR). Insulin produced a dose-dependent reduction of RR when added to the perfusate at concentrations between 10 and 1,000 microU/ml. When kidneys were perfused with a calcium-free perfusate, RR increased nearly fivefold. Insulin (1,000 microU/ml) not only failed to suppress RR in calcium-free perfusions but stimulated it. The addition of verapamil (10(-5) M) to the perfusate likewise prevented the insulin inhibition of RR. Perfusion without potassium reduced RR to one-third of control values. The addition of insulin to kidneys perfused without potassium further suppresses RR. We conclude that at concentrations similar to those found in plasma, insulin modulates renin secretion. This process requires the influx of calcium possibly through insulin receptor-operated channels.
Interactions of cold exposure and starvation on glucose tolerance and insulin response
Authors: Vallerand A. L. , Lupien J. , Bukowiecki L. J.
Published: December 2017

The metabolic interactions of cold exposure, cold acclimation, and starvation on glucose tolerance and plasma insulin levels were studied in precannulated, unrestrained, and unanesthetized rats. Cold exposure (48 h at 5 degrees C) significantly reduced the insulin response to intravenous glucose injection (P less than 0.01) while improving glucose tolerance (P less than 0.01). Starvation (48 h at 25 degrees C) also reduced the insulin response (P less than 0.01) but did not significantly alter glucose tolerance. “Accelerated starvation” induced by starving rats for 48 h at 5 degrees C dramatically reduced both basal and glucose-stimulated insulin levels while even improving glucose tolerance, resulting in a 15-fold reduction in the insulinogenic index. Cold acclimation (3 wk at 5 degrees C) induced essentially the same alterations as cold exposure. Approximately reversed changes were observed when cold-acclimated rats were returned to a warm environment for 15–18 h. Results from these studies indicate that 1) cold exposure and starvation, but not cold acclimation, act synergistically in decreasing the sensitivity and/or the capacity of pancreatic islets for secreting insulin in response to glucose stimulation; 2) glucose tolerance and possibly insulin sensitivity of peripheral tissues are enhanced by cold exposure and starvation, although glucose tolerance is improved by cold exposure only, not by starvation; 3) an improved glucose tolerance with barely detectable plasma insulin levels was obtained in cold-starved rats under normal physiological conditions.
Actions of neurohypophysial peptides on pancreatic hormone release
Authors: Dunning B. E. , Moltz J. H. , Fawcett C. P.
Published: December 2017

The intermittent reports concerning metabolic actions of neurohypophysial extracts or hormones encouraged us to study the effect of these substances on the function of the endocrine pancreas. A surprisingly small amount of neural lobe (NL) extract (0.025 NL eq/ml) stimulated a 425% increase in the release of glucagon from islets isolated from the pancreas of the rat. Gel filtration of the extract produced an elution profile of glucagon-releasing activity that was superimposable on the profiles of oxytocin (OT) and arginine vasopressin (AVP). Synthetic OT and AVP each elicited a concentration-dependent stimulation of glucagon release but failed to influence insulin release in medium 199 containing 5.6 mM glucose. They were effective at 0.2 ng/ml (+55%, +50%) and produced a striking increase (five- to sevenfold) at 20 ng/ml. The response to each peptide was greatly diminished in the presence of a higher concentration of glucose (11 mM). The lysine, desamino-, and 1,6-aminosuberyl analogues of vasopressin, vasotocin, and AVP are equipotent peptides, whereas the desglycinamide analogue, pressinoic acid, and angiotensin II were inactive. Injection of AVP (1 microgram iv) produced a rapid increase in peripheral glucagon (+185% in 5 min). The response to injection of OT was less rapid (+105% in 15 min), but in each case elevation of insulin was also observed. Our results provide evidence that OT and AVP can act directly on the endocrine pancreas and may help explain previous reports of metabolic actions of these peptides.
Ovine placental lactogen stimulates glycogen synthesis in fetal rat hepatocytes
Authors: Freemark M. , Handwerger S.
Published: December 2017

The effects of placental lactogen on glycogen metabolism have been studied in cultured hepatocytes from 20-day-old fetal rats. Ovine placental lactogen (oPL; 2, 5, 10, and 25 micrograms/ml) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen and total cellular glycogen content after 4 h of incubation but had no effect on glycogen degradation. Half-maximal stimulation occurred with an oPL concentration of 3 micrograms/ml. In contrast, human placental lactogen had no effect on [14C]glucose incorporation into glycogen. Ovine growth hormone (50 and 100 micrograms/ml), rat growth hormone (20, 40, and 100 micrograms/ml), and ovine prolactin (10, 40, and 100 micrograms/ml) stimulated dose-dependent increases in [14C]glucose incorporation into glycogen, but the potencies of these hormones were only 10-20% of that of oPL. Insulin (20 nM) stimulated [14C]glucose incorporation into glycogen, whereas glucagon (0.5 and 20 nM) inhibited [14C]glucose incorporation into glycogen and increased glycogen degradation. Our findings suggest that oPL may have direct insulin-like effects on carbohydrate metabolism in the fetus and that oPL may contribute to the accumulation of fetal liver glycogen that occurs in late gestation.
LH responses to LHRH in perifused pituitary cell culture: sex differences in the rat
Authors: Loughlin J. S. , Naddaff P. G. , Badger T. M.
Published: December 2017

The present experiments were designed to study male and female luteinizing hormone (LH) secretory patterns following pulsatile or continuous LH-releasing hormone (LHRH) administration using a perifused dispersed rat anterior pituitary cell culture system. In male cells, consistent LH responses were elicited by hourly LHRH pulses (30 pmol), whereas in the female cells (proestrus or diestrus I), a statistically significant (P less than or equal to 0.01) decrease in the LH secretion occurred with successive LHRH pulses. Proestrous cells secreted significantly (P less than or equal to 0.01) more LH than diestrous cells during the first 24 h but not after 48 h in culture. When exposed to a 6-h continuous infusion of LHRH (10 nM), male cells released LH in a single phase and female cells secreted LH in a biphasic pattern. These data suggest that significant sex differences exist in the rat LH secretory pattern elicited by LHRH in vitro.
Inhibitory effect of plasma free fatty acids on glucose production in the conscious dog
Authors: Wolfe R. R. , Shaw J. H.
Published: December 2017

We have previously reported that, in conscious, unrestrained dogs in which insulin and glucagon levels were clamped pharmacologically, combined alpha- and beta-adrenergic blockade resulted simultaneously in a fall in plasma free fatty acid (FFA) levels and an increase in glucose production. In this study we have tested the hypothesis that the increase in glucose production observed in the previous study was due to the fall in plasma FFA concentration. Glucose production was measured by means of the primed-constant infusion of [6-3H]- and/or [U-14C]glucose, and insulin and glucagon were clamped at constant levels by means of the infusion of somatostatin, insulin, and glucagon. When no attempt was made to control the FFA levels, combined alpha- and beta-adrenergic blockade significantly decreased plasma FFA levels, and this was associated with a significant increase in the rate of glucose production. However, the glucose production response to adrenergic blockade was entirely prevented by the clamping of FFA levels at a high, constant value by the infusion of a 10% lipid emulsion (Liposyn) and heparin. We conclude that basal adrenergic activity is important in the mobilization of fat but does not directly influence glucose production. Further, there is an inhibitory effect of FFA on glucose production that is unmasked during hormonal control and alpha- and beta-adrenergic blockade.
Effect of exogenous vasopressin on vasopressin release
Authors: Engel P. A. , Rowe J. W. , Minaker K. L. , Robertson G. L.
Published: December 2017

To characterize the influence of extracellular volume status on vasopressin pharmacokinetics, eleven young (aged 19-31 yr) and four old (aged 62-80 yr) subjects received bolus injections of 1 mU/kg Pitressin or synthetic arginine vasopressin following 6 days of sodium depletion (10 meq Na/day) or sodium loading (250 meq Na/day). In six young subjects the rapid decline in plasma vasopressin (pAVP) following the initial peak was interrupted by a second peak 5-30 pg/ml in magnitude 7.5-20 min after injection. In four of these subjects the second peak was larger following sodium depletion as compared with sodium loading. In the elderly a small (4 pg/ml) second peak was present in one sodium-depleted subject. Of five sodium-depleted subjects with central diabetes insipidus, none showed a secondary rise in pAVP. These results indicate that exogenous vasopressin may stimulate the release of endogenous AVP, an effect that appears to be enhanced by sodium depletion and is virtually absent in the elderly. There was no effect of age, volume status, or diabetes insipidus on AVP pharmacokinetics.