bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of adult rat cardiomyocytes to study cardiac glycogen metabolism
Authors: Wolleben C. D. , Jaspers S. R. , Miller T. B.
Published: December 2017

The use of adult rat cardiomyocytes to model cardiac glycogen metabolism was investigated by monitoring the response of glycogen phosphorylase and glycogen synthase to epinephrine and insulin treatment. Cardiomyocytes derived from normal rats respond to epinephrine in the range of 1 X 10(-7) to 5.5 X 10(-6) M epinephrine with an increase in the percent of phosphorylase in the AMP-independent form from 11.5 to 24.8%. In the same cells, insulin in the range of 10(-9) to 10(-7) M increased the glucose 6-phosphate independent form of glycogen synthase from 30.5 to 40.5%. Cells derived from alloxan-diabetic hearts exhibit a hypersensitive phosphorylase activation and a refractile synthase inactivation in response to epinephrine treatment. This pattern is similar to that recorded using perfused heart preparations. The data presented suggests that adult rat cardiomyocytes represent a valid model of glycogen metabolism in both the normal and alloxan-diabetic rat.
A potential mechanism of DL-beta-hydroxybutyrate-induced malformations in mouse embryos
Authors: Hunter E. S. , Sadler T. W. , Wynn R. E.
Published: December 2017

DL-beta-Hydroxybutyrate (DL-BOHB) is teratogenic to rodent embryos in culture, but the biochemical mechanism(s) responsible for the induction of malformations has not been elucidated. Thus, to delineate a potential mechanism, the interaction of the ketone body with embryonic glucose metabolism was investigated. Mouse embryos were exposed in whole embryo culture to DL-BOHB or each isomer separately during the period of neurulation. The results demonstrate that DL-BOHB inhibits glucose oxidation by the pentose phosphate pathway (PPP) with no concomitant effect on Krebs cycle or glycolysis. Furthermore, decreased rates of embryonic uridine monophosphate and DNA synthesis were produced by DL-BOHB, whereas orotate synthesis was unaffected, thereby suggesting that the availability of ribose moieties synthesized by the PPP was compromised. This hypothesis was supported by the observation that addition of ribose to DL-BOHB-containing medium reduced the incidence of ketone body-induced neural tube defects and maintained the rates of DNA synthesis at control levels. Furthermore, these biochemical alterations are due to the synergistic effects of the D and L isomers and may be related to changes in redox states.
IP3-dependent Ca2+ release in permeabilized hepatocytes of endotoxemic and septic rats
Authors: Spitzer J. A. , Deaciuc I. V.
Published: December 2017

Inositol trisphosphate-dependent Ca2+ release was measured in saponin-permeabilized hepatocytes isolated from acutely (2 mg/100 g body wt iv) or chronically (0.1 mg X 100 g body wt-1 X 24 h-1 for 30 h) endotoxin-treated (ET, Escherichia coli) rats or from animals rendered septic by cecal ligation and puncture. A decrease of this parameter was observed in acutely ET-treated rats (52%, P less than 0.01) and after 30 h of continuous ET infusion (33%, P less than 0.01). Sepsis was associated with an elevated Ca2+ release (34%, P less than 0.01) as compared with the sham-operated animals. We conclude that during endotoxicosis and sepsis alterations of intracellular Ca homeostasis take place, reaching sites beyond the level of the plasma membrane. Such alterations could account in part for metabolic and functional changes associated with these pathologic states. In addition, ET treatment provides the first known intervention resulting in the modulation of inositol trisphosphate-dependent Ca2+ release.
Ionophore A23187 partially reverses LH secretory defect of pituitary cells from old rats
Authors: Chuknyiska R. S. , Blackman M. R. , Roth G. S.
Published: December 2017

We measured in vitro release of luteinizing hormone (LH) in the presence of 1.5 mM extracellular calcium, with and without LH-releasing hormone (LHRH; 10(-10) to 10(-7) M) or the ionophore A23187 (10(-7) to 10(-4) M), in primary cultures of anterior pituitary cells from intact mature (6 mo) and old (24 mo) male and intact and ovariectomized mature and old female Wistar rats. Base-line as well as LHRH- and A23187-mediated LH secretion was decreased from cells of old rats. However, exposure to A23187 led to a nearly twofold greater augmentation of LH release from cells of old rats, thus decreasing the apparent age-related LH secretory deficit by approximately one-half. We then measured LHRH-mediated (10(-8) M) vs. A23187-mediated (10(-4) M) LH release with and without extracellular calcium (0.08-1.5 mM). For cells from both mature and old rats, there was a similar calcium dependency for A23187- and LHRH-mediated LH release, with optimal LH secretion at 1.0-1.5 mM extracellular calcium concentrations. Again, both LHRH- and A23187-stimulated LH release was significantly lower and exposure to A23187 led to a greater increase in LH release from cells of old rats. Taken together with similar findings in other systems, these data suggest that the in vitro LH secretory defect of pituitary cells from old rats results in part from one or more defects in calcium mobilization and that such alterations may be a widespread manifestation of aging.
Leucine metabolism in human newborns
Authors: Denne S. C. , Kalhan S. C.
Published: December 2017

The present study was designed to 1) determine whether a relationship exists between newborn birth weight and leucine metabolism and 2) compare leucine and energy metabolism in a period of rapid growth and development (i.e., newborn) with a constant nongrowth period (i.e., adult). Leucine kinetics and energy expenditure were measured in the postabsorptive state in 12 normal full-term newborns in early neonatal life and in 11 normal adults using a primed constant L-[1-13C]leucine infusion combined with respiratory calorimetry. A significant positive correlation between newborn birth weight and leucine flux was observed. Leucine flux per kilogram body weight was significantly greater in newborns compared with adults, as was leucine oxidation and energy expenditure. When normalized to metabolic body weight (W0.75), newborns and adults had similar rates of energy expenditure, leucine flux, and oxidation. The allometric exponent relating leucine flux to body weight (0.80) was nearly equivalent to that describing the energy expenditure-to-body weight relationship (0.79) and both were similar to the 0.75 metabolic weight exponent. These data suggest the following. 1) A relationship exists between newborn birth weight and protein metabolism, as reflected by the correlation between leucine flux when expressed as micromoles per kilogram per hour and birth weight. It is speculated that this relationship may be the result of differences in previous protein and energy supplies. 2) The high rate of leucine flux measured in newborns probably reflects the rapid remodeling of protein that occurs in this period of development, even during fasting.(ABSTRACT TRUNCATED AT 250 WORDS)
Glucagon infusion increases rate of purine synthesis de novo in rat liver
Authors: Itakura M. , Maeda N. , Tsuchiya M. , Yamashita K.
Published: December 2017

Based on the parallel increases of glucagon, the second peak of hepatic cAMP, and the rate of purine synthesis de novo in the prereplicative period in regenerating rat liver after a 70% hepatectomy, it was hypothesized that glucagon is responsible for the increased rate of purine synthesis de novo. To test this hypothesis, the effect of glucagon or dibutyryl cAMP infusion on the rate of purine synthesis de novo in rat liver was studied. Glucagon infusion but not insulin or glucose infusion increased the rate of purine synthesis de novo, which was assayed by [14C]glycine or [14C]formate incorporation, by 2.7- to 4.3-fold. Glucagon infusion increased cAMP concentrations by 4.9-fold and 5-phosphoribosyl-1-pyrophosphate concentrations by 1.5-fold in liver but did not change the specific activity of amidophosphoribosyltransferase (EC 2.4.2.14) or purine ribonucleotide concentrations. Dibutyryl cAMP infusion also increased the rate of purine synthesis de novo by 2.2- to 4.0-fold. Because glucagon infusion increased the rate of purine synthesis de novo in the presence of unchanged purine ribonucleotide concentrations, it is concluded that glucagon after infusion or in animals after a 70% hepatectomy is playing an anabolic role to increase the rate of purine synthesis de novo by increasing cAMP and 5-phosphoribosyl-1-pyrophosphate concentrations.
Effect of sampling site on early kinetics of blood radioiodide and pertechnetate
Authors: Hays M. T. , Carr L. J. , Turrel J. M.
Published: December 2017

Radioiodide (I) and radiopertechnetate (TcO4) were sampled simultaneously from left ventricle, right atrium, and femoral vein early after intravenous injection to pentobarbital sodium-anesthetized cats. Concentrations of both tracers in femoral vein blood was lower than in left ventricular (arterial) blood, with rapid narrowing of the differences over 20 min and gradual approach to steady state. Right atrial blood concentrations were intermediate. When these data were fitted to three-compartment mamillary models, representing blood and tissue pools, compartment size and kinetics differed according to which sampling site was taken as representative of each cat's blood. We have developed a model incorporating subcompartmentalization of the blood with an exchange compartment connecting to the pulmonary circulation as well as compartments exchanging with peripheral sites. With the use of this model, all data sets fitted well. The pulmonary exchange compartment and a large rapid exchange compartment in the femoral vein drainage areas are essential to reconciling the differences among sampling sites.
Physiology and pathophysiology of atrial peptides
Authors: Goetz K. L.
Published: December 2017

The atria secrete atrial peptides (atriopeptins) that are capable of producing dramatic alterations in a number of body processes. Secretion of atriopeptin appears to be regulated primarily by the prevailing pressure within the atria. In pharmacological doses, atriopeptin rapidly elicits a natriuresis when administered to experimental animals or humans. In contrast, infusion rates that increase plasma atriopeptin only by about three- to fivefold tend to produce a slowly developing and modest diuresis. Evidence examined in this review suggests that the atrial peptides are not potent natriuretic substances under normal physiological conditions, although it is likely that they exert a modulating influence on sodium excretion. The atrial peptides are vasoactive and induce a number of cardiovascular changes including decreases in arterial blood pressure, cardiac filling pressure, and cardiac output and a translocation of fluid from plasma to the interstitial fluid space. They also interact with other hormones, particularly the renin-angiotensin-aldosterone system. Finally, atriopeptin is distributed throughout many regions of the brain where it may serve as a neuromodulator or neurotransmitter. Atriopeptin circulating in the bloodstream also may influence cerebral mechanisms by acting on receptors in the circumventricular organs. A more complete understanding of the diverse effects of this cardiac endocrine system is expected to provide further insight into a spectrum of physiological and pathophysiological processes.
Compliance in microcomputer-assisted conventional insulin therapy: computer simulation study results
Authors: Sozzi S. , Strack T. , Schulz M. , Albisser A. M.
Published: December 2017

Compliance in diabetes self-management is a complex issue. It involves the interdependent daily actions of self-measurement of blood glucose and adherence to a prescribed schedule of daily activities. This impacts strongly on lifestyle because it necessitates precise meal timing as well as control of size and carbohydrate content. We sought to identify how strongly relaxing the lifestyle constraints per se would impact the ability to achieve improved metabolic control. To isolate these effects from those that result from poor measurement compliance, we used a computer simulator called OMNI et al. Furthermore, to standardize the "clinical" therapy, a second microprocessor device called an "Insulin Dosage Computer" was used to adjust insulin doses based on the usual clinical practice of four times a day precibal blood glucose measurements. Ten type 1 diabetic patients were stimulated and each followed for 120 simulated days. In each such subject, the simulation was repeated three times to include three different levels of lifestyle compliance ranging from excellent to poor. In all three protocols, starting from a level of poor control of diabetes, mean blood glucose values were significantly improved without significant differences after 120 days of computer-simulated treatment. Only the standard deviations, expressing the fluctuations of blood glucose and hence its stability, increased with decreasing lifestyle compliance. This computer simulation predicts that consistent self-monitoring of four blood glucose values per day is the cornerstone of diabetic self-control and that the use of these data according to a standardized therapeutic algorithm for insulin adjustment may successfully stabilize even patients with poor lifestyle compliance. Clinical studies must follow.
Relationships between cell surface insulin binding and endocytosis in adipocytes
Authors: Jochen A. L.
Published: December 2017

Chymotrypsin substrate analogues, such as N-acetyl-Tyr ethyl ester, have recently been demonstrated to inhibit the endocytic uptake of insulin in isolated rat adipocytes. In this study, the effects of N-acetyl-Tyr ethyl ester on cell surface insulin binding and dissociation were examined. Surface-bound 125I-insulin was distinguished from intracellular 125I-insulin by the sensitivity of the former to rapid dissociation with an acidic buffer (pH 3.0). Plateau levels of surface-bound insulin at 37 degrees C were increased 70% by inhibiting the internalization pathway. This increase was temperature and insulin concentration dependent. Thus differences in surface binding were small at 12 degrees C and also at high (100-200 ng/ml) insulin concentrations. Inhibition of internalization with N-acetyl-Tyr ethyl ester markedly slowed the loss of surface-bound insulin observed during dissociation studies. After 20-30 min of dissociation, the remaining levels of surface-bound insulin were three- to fourfold higher in treated adipocytes compared with control adipocytes. Added unlabeled insulin retained its ability to accelerate the dissociation of insulin in N-acetyl-Tyr ethyl ester-treated cells. These observations indicate that the internalization pathway is a quantitatively important factor in determining levels of surface binding at 37 degrees C and in determining the rate of deactivation of insulin binding.
Effect of hyperglucagonemia on whole-body leucine metabolism in immature pigs before and during a meal
Authors: Ostaszewski P. , Nissen S.
Published: December 2017

Leucine metabolism was measured isotopically in 12 immature female pigs to assess the effect of acute hyperglucagonemia on leucine kinetics in both the fed and fasting states. After an overnight fast, immature pigs were infused with alpha-[3H]ketoisocaproate and [14C]leucine. After a 2-h equilibration period, an infusion of either saline or 7 pg.kg-1.min-1 of glucagon was begun, which increased plasma glucagon from approximately 140 to approximately 640 pg/ml and doubled the insulin concentrations. Two hours later, pigs were fed small meals to which [5,5,5-2H3]leucine was added to trace absorption. By subtracting absorption from total leucine flux, an estimate of endogenous proteolysis during the meal was made. In the fasting state, glucagon increased proteolysis, relative to controls, by approximately 20% (P less than 0.05) and increased oxidation by approximately 50% (P less than 0.05). No significant glucagon-related changes in any other flux parameters occurred in the fasting state. Ingestion of the meals caused oxidation to increase 41% in control animals, whereas in glucagon-infused animals, oxidation increased 84% (P less than 0.05 control vs. glucagon response to meal). Additionally, animals infused with glucagon suppressed endogenous proteolysis 43% after the meal compared with a 55% decrease in control animals (P less than 0.05 basal period vs. fed period). These data indicate that glucagon stimulates whole-body proteolysis in both the fasting and fed states.
Mitochondrial membrane transitions in heart and other organs of a hibernator
Authors: Raison J. K. , Augee M. L. , Aloia R. C.
Published: December 2017

Critical temperatures (T) for transitions in both lipid structure and enzyme function of mitochondrial membranes from liver, kidney, brown fat, and heart tissues were determined for the hibernator Spermophilus lateralis at two weekly intervals from early summer to late autumn and during hibernation. For all tissues T fell into one of three groups: those below 4 degrees C (the minimal level of accurate determination), those centered about a mean of 11.9 +/- 1.4 degrees C, and those centered about a mean of 20.9 +/- 1.8 degrees C. The T for tissues from torpid animals and from heart, at all sampling periods, was below 4 degrees C. For liver, kidney, and brown fat the mean T was approximately 21 degrees C in early summer but was lowered later in the season in a two-step process, falling to below 4 degrees C before the animals were exposed to cold and entering torpor. It is concluded that for mitochondria the thermal response of the membrane lipids is altered such that the transition in structure and function is always below the minimum body temperature likely to be experienced by this animal. Heart tissue is exceptional in that the transition is at a temperature consistent with a body temperature of torpor even in summer-active animals.
VIP and its homologues increase vascular conductance in certain endocrine and exocrine glands
Authors: Huffman L. J. , Connors J. M. , Hedge G. A.
Published: December 2017

The effects of vasoactive intestinal peptide (VIP) and related structural homologues on tissue vascular conductances were investigated in anesthetized male rats. VIP, peptide histidine isoleucine (PHI), secretin, growth hormone-releasing factor (GHRF), gastric inhibitory peptide (GIP), or saline was infused intravenously over 4 min. Tissue blood flows were measured during this time by use of 141Ce-labeled microspheres. Regional blood flows were normalized for any change in mean arterial blood pressure during infusions, and results were expressed in terms of tissue vascular conductance (C). Circulating thyrotropin (TSH), triiodothyronine (T3), and thyroxine (T4) levels were determined before and at 20 min and 2 h after treatment. Marked increases in thyroid, pancreatic, and salivary gland vascular Cs occurred during peptide infusions with the order of potency (VIP greater than PHI greater than secretin greater than GHRF greater than GIP) correlating with the degree of structural homology to VIP. PHI and secretin produced maximal increases in vascular Cs, which were the same as those obtained with VIP. Circulating TSH, T3, and T4 levels were not different from values in saline-infused rats after peptide treatments that caused striking increases in thyroid vascular C. In the adrenal, kidney, and testis, VIP and its homologues had little to no effect on vascular Cs. We subsequently measured regional vascular Cs during VIP infusions in the presence or absence of secretin.(ABSTRACT TRUNCATED AT 250 WORDS)
Dual role of glucocorticoids in regulation of pituitary content and secretion of gonadotropins
Authors: Suter D. E. , Schwartz N. B. , Ringstrom S. J.
Published: December 2017

To verify the inhibitory effect of cortisol (F) on secretion of luteinizing hormone (LH) 24 h postorchidectomy, we implanted cholesterol (C) or F subcutaneously into male rats, and 4 days later orchidectomized or sham orchidectomized them under ether anesthesia. We injected gonadotropin-releasing hormone (GnRH) or saline into these rats 24 h postorchidectomy, collected blood 30 min later, and measured LH and follicle-stimulating hormone (FSH) in serum and pituitaries. F inhibited GnRH-induced secretion of LH without affecting secretion of FSH. We then implanted C, corticosterone (B), or F into rats, performed the same surgeries, and collected pituitaries 24 h after surgery for quantitation of receptors for GnRH. Neither F nor B affected the number of receptors for GnRH or their affinity for a GnRH analogue. Suppression of LH in serum occurred without decreased pituitary content of LH. In contrast, F increased pituitary content of FSH. Implantation of progesterone in a similar experiment did not affect circulating concentrations or pituitary contents of FSH or LH. These data suggest that glucocorticoids may inhibit responsiveness to GnRH by some mechanism distal to the receptor for GnRH that affects only LH.
Preservation of insulin effects on glucose production and proteolysis during fasting
Authors: Jensen M. D. , Miles J. M. , Gerich J. E. , Cryer P. E. , Haymond M. W.
Published: December 2017

To determine whether fasting alters the ability of insulin to suppress endogenous glucose production or proteolysis, isotopic flux measurements of glucose, leucine, alpha-keto-isocaproate, and alanine were made in 13 normal volunteers after a 14-h (day 1) and an 84-h (day 4) fast. Using the “pancreatic clamp” technique, we achieved small increments in plasma insulin concentrations, as well as constant and identical plasma hormone and glucose concentrations, on both study days in seven subjects. The remaining six subjects were infused with saline and served as controls. Leucine rate of appearance (an index of proteolysis) was greater on day 4 than on day 1 (P less than 0.001), but decreased to equal values during the pancreatic clamp on each study day. During the pancreatic clamp, endogenous glucose production decreased to lesser (P less than 0.005) values on day 4 than on day 1. In conclusion, insulin suppresses proteolysis equally well before and after brief fasting, and endogenous glucose production is more completely suppressed by insulin after brief fasting than after an overnight fast.
Ontogenesis of epidermal growth factor in liver of BALB mice
Authors: Laborde N. P. , Grodin M. , Buenaflor G. , Brown P. , Fisher D. A.
Published: December 2017

To characterize the ontogenesis of hepatic epidermal growth factor (EGF) metabolism in normal BALB mice, we measured serum and liver concentrations of EGF and liver concentrations of pre-pro EGF mRNA. Female and male animals were studied at 1, 2, 5, 7, and 10 wk of life. After death, body weight and length were measured, and serum and liver tissues were collected for EGF determinations. Immunoreactive serum EGF (means +/- SE) increased at 7 and 10 wk and was significantly higher (P less than 0.05) in males (465 +/- 58 and 683 +/- 120 pg/ml) than females (188 +/- 52 and 295 +/- 64 pg/ml). Liver EGF concentrations were low at 1, 2, and 5 wk, significantly increasing (P less than 0.01) at 10 wk to 179 +/- 36 vs. 268 +/- 49 pg/mg protein for females and males, respectively (female and male values were significantly different, P less than 0.01). Pre-pro EGF mRNA was examined at 1, 2, 3, 5, 7 and 10 wk. EGF message increased in liver to highest values at 10 wk in both males and females. There was a high correlation between serum and liver EGF concentrations during the first 10 wk (r = 0.97 and 0.85 for males and females, respectively) and a twofold increase in liver EGF mRNA between 3 and 10 wk of postnatal life. These results suggest that liver may be an important source of circulating EGF in developing BALB mice.
Effects of somatostatin and glucose infusion on glucose kinetics in fetal sheep
Authors: Bloch C. A. , Menon R. K. , Sperling M. A.
Published: December 2017

We examined the contribution of glucose, independently of insulin, on fetal glucose kinetics in the sheep by infusing somatostatin (SRIF), followed by SRIF plus glucose (protocol A) or reversing the initial infusion sequence (protocol B). In protocol A (n = 8), infusion of SRIF at 200 micrograms/h decreased plasma insulin (IRI) and blood glucose (G) by 2.8 +/- 1.0 microU/ml and 1.34 +/- 0.2 mg/dl from their respective basal concentrations of 6.8 +/- 1.4 microU/ml and 16.47 +/- 0.91 mg/dl (P less than 0.05; P less than 0.005). There were no significant changes in plasma glucagon (IRG) or the rates of umbilical G uptake or of G utilization, but G turnover decreased by 1.77 +/- 0.34 mg.kg-1.min-1 (P less than 0.005). Addition of G at a rate of 5.6 +/- 0.8 mg.kg-1.min-1 had no effect on IRI and IRG. Total G uptake (G infusion rate plus umbilical G uptake) increased from 6.37 +/- 0.77 to 10.25 +/- 1.0 mg.kg-1.min-1 (P less than 0.01), despite suppression of umbilical G uptake by 33%. Fetal G reached a new steady state of 23.08 +/- 1.37 mg/dl, and G turnover increased by 4.81 +/- 0.96 mg.kg-1.min-1 from its SRIF-induced nadir (P less than 0.005). Since G concentration was maintained at steady state, the rate of G utilization was equivalent to the rate of total G uptake, an increase of 60% from basal despite suppressed IRI.(ABSTRACT TRUNCATED AT 250 WORDS)
Measuring tracee turnover from tracer specific activity in the steady state
Authors: Lehman S. L. , Stanley W. C.
Published: December 2017

When a substrate appears in and disappears from an unmeasured (tissue) compartment, the proper sites for tracer infusion and sampling to measure tracee turnover become controversial. We analyze a three-compartment model representing arterial blood, tissue, and venous blood. The desired quantity, tracee turnover, is the ratio of the steady-state infusion rate to tissue specific activity. However, specific activity in the tissue compartment is unknown. We assume infusion of tracer into the arterial pool at a constant rate and consider sampling of specific activity of either blood compartment in the steady state. We obtain estimates of tissue specific activity from measurement of concentrations of tracer and tracee in blood samples in two extreme cases. In case I, tracee is assumed to appear in the venous compartment but to disappear from the tissue pool. Then tissue specific activity is equal to arterial specific activity. In case II, both appearance and disappearance are from the tissue pool. Tissue specific activity is then less than arterial or venous specific activity. We give formulas for the difference in each case. We discuss the relationship of our models to actual tracer experiments and define physiological locations for our three compartments. Appearance of substrates is probably intermediate between our extreme cases. A numerical estimate of turnover for the substrate lactate in resting humans reveals an error bound of approximately 30%. We discuss sites of infusion and sampling consistent with our model, the effects of relaxing some of our modeling constraints, and experimental necessities for getting beyond the steady state.
Responsiveness of isolated adrenocortical cells from lean and obese Zucker rats to ACTH
Authors: White B. D. , Davenport W. D. , Porter J. R.
Published: December 2017

Morning plasma corticosterone concentrations have been reported to be elevated in obese Zucker rats compared with lean rats. The aim of this study was to determine if differences in adrenal sensitivity or maximal responsiveness to adrenocorticotropic hormone (ACTH)-(1-24) could account for this disparity. Serum and adrenal glands were collected from lean and obese, male and female Zucker rats (10-13 wk old) between 10:00 and 11:00 A.M. Adrenocortical cells were isolated and challenged with ACTH-(1-24). The serum corticosterone and ACTH concentrations were significantly greater in obese males compared with lean males (45.3 +/- 10.3 vs. 23.2 +/- 1.45 ng/ml and 156.6 +/- 15.3 vs. 113.3 +/- 9.4 pg/ml, respectively). Although serum corticosterone concentrations were similar in female rats, serum ACTH concentrations tended (P = 0.07) to be lower in obese female rats than in lean female rats (67.6 +/- 9.3 vs. 103.5 +/- 15.1 pg/ml, respectively). The median effective concentration (EC50) and the maximal corticosterone response per microgram of DNA of dose-response curves derived from lean and obese rats were not significantly different. Additionally, a morphometric evaluation of adrenal tissue from lean and obese rats suggested that cells of the zona glomerulosa were smaller in obese rats than in lean rats. Our data confirm that morning serum corticosterone concentrations are elevated in 10- to 13-wk-old male Zucker rats. This difference does not appear to be due to differences in the sensitivity or maximal secreting capacity of adrenocortical cells to ACTH.
Effect of sex steroids on peak bone density of growing rabbits
Authors: Gilsanz V. , Roe T. F. , Gibbens D. T. , Schulz E. E. , Carlson M. E. , Gonzalez O. , Boechat M. I.
Published: December 2017

To determine the effect of sex hormones on bone density (BD) during growth, longitudinal quantitative computed tomography (QCT) measurements were obtained in growing, castrated New Zealand White rabbits following administration of normal saline, testosterone, or estrogen from 6 wk of age until the time of skeletal maturity. Vertebral QCT densities increased during growth, were highest at the time of epiphyseal closure, and were significantly greater (P less than 0.001) in hormone-treated animals. In vivo QCT measurements in 12 vertebraes correlated strongly (r = 0.92) with percentage of calcium per weight assessed in vitro by neutron activation analysis.
Insulin responsiveness of protein metabolism in vivo following bedrest in humans
Authors: Shangraw R. E. , Stuart C. A. , Prince M. J. , Peters E. J. , Wolfe R. R.
Published: December 2017

To test the influence of bedrest on insulin regulation of leucine metabolism, six normal young men were subjected to a five-step hyperinsulinemic euglycemic clamp before and after 7 days of strict bedrest. A primed-constant infusion of [1-13C]leucine at 0.12 +/- 0.02 mumol.kg-1.min-1 was used. Before bedrest, the basal rate of appearance (Ra) of intracellular leucine and leucine oxidation were 2.79 +/- 0.17 and 0.613 +/- 0.070 mumol.kg-1.min-1, respectively. Insulin caused a dose-dependent reduction of the intracellular leucine Ra and leucine oxidation to a minimum of 1.64 +/- 0.08 and 0.322 +/- 0.039 mumol.kg-1.min-1, respectively, in nonbedrested subjects (P less than 0.001). Insulin also caused a dose-dependent reduction of plasma leucine concentration from 95 +/- 4 to 38 +/- 2 mumol/l (P less than 0.001). After bedrest, subjects exhibited decreased glucose tolerance and increased endogenous insulin secretion, but basal and insulin-suppressed intracellular leucine Ra and leucine oxidation rates were not different from control. Magnetic resonance imaging of the back and lower extremities revealed a 1-4% decrease in muscle volume and a 2-5% increase in fat volume secondary to bedrest. Bedrest also resulted in a negative nitrogen balance as compared with the control period, with an average cumulative loss of 6.3 g of nitrogen after 6 days. Urinary 3-methyl-L-histidine excretion was unchanged by bed rest. Thus because negative nitrogen balance and skeletal muscle atrophy occurred in six rested subjects in the absence of changes in the two indices of protein breakdown used in this study (3-methyl-L-histidine release and leucine release), it seems likely that muscle protein synthesis was inhibited.
Adrenergic control of renin in euhydrated and water-deprived conscious dogs
Authors: Chen Y. H. , Hisa H. , Radke K. J. , Izzo J. L. , Sladek C. D. , Blair M. L.
Published: December 2017

These experiments evaluated the relative contributions of alpha- and beta-adrenoceptors to control of plasma renin activity (PRA) in conscious dogs in which PRA was elevated to two- and threefold basal levels by the orthostatic stress of passive quadruped standing and by 24-h water deprivation. All dogs were uninephrectomized and surgically prepared with chronically indwelling catheters in the aorta, vena cava, and remaining renal artery at least 10 days before experiments. Simultaneous direct renal arterial (ia) infusion of phenoxybenzamine and propranolol decreased PRA by 50% in euhydrated standing dogs and by 70% in dehydrated standing dogs without changing mean arterial pressure or heart rate. In euhydrated dogs, both ia phenoxybenzamine alone and ia propranolol alone significantly decreased PRA, but the effect of propranolol was greater than that of phenoxybenzamine. In dehydrated dogs, ia infusion of phenoxybenzamine alone did not significantly decrease PRA, whereas propranolol alone decreased PRA to nearly the same extent as combined ia alpha- and beta-adrenoceptor blockade. The majority of the adrenergically mediated component of PRA observed during orthostatic stress and dehydration in conscious dogs is therefore mediated by beta-adrenoceptors. However, PRA was similarly reduced whether propranolol was infused ia or intravenously. Thus the site of action of propranolol (intrarenal vs. extrarenal) could not be identified by these experiments.
Abnormal regulation of cAMP accumulation in pancreatic islets of obese mice
Authors: Black M. A. , Heick H. M. , Begin-Heick N.
Published: December 2017

The present study was undertaken 1) to determine whether a defect in the regulation of adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was present in the beta-cell of the ob/ob mouse, 2) to determine how such a defect, if present, would alter the regulation of insulin secretion in these islets, and 3) to find out if epinephrine had similar effects on insulin secretion and cAMP production in islets of lean and obese mice. In the obese mouse, inhibitory modulators neither inhibited cAMP accumulation in intact islets nor adenylate cyclase activity in islet homogenates. These anomalies in the modulation of cAMP accumulation were not correlated with a failure to inhibit insulin secretion. It is concluded that, first, a defect in cAMP modulation is present in the islets of Langerhans of the obese mouse; second, epinephrine produces its effects on insulin secretion and cAMP accumulation via distinct mediators; and third, an anomaly in the adenylate cyclase system is unlikely to be the cause of the exaggerated insulin secretion in the islet of the ob/ob mouse. It is more likely that the exaggerated insulin secretion is due to a faulty cation gating mechanism that, in turn, may contribute to the impaired ability of the islet to accumulate cAMP.
Selective induction of high-ouabain-affinity isoform of Na+-K+-ATPase by thyroid hormone
Authors: Haber R. S. , Loeb J. N.
Published: December 2017

The administration of thyroid hormone is known to result in an induction of the Na+-K+-adenosinetriphosphatase (Na+-K+-ATPase) in rat skeletal muscle and other thyroid hormone-responsive tissues. Since the Na+-K+-ATPase in a variety of mammalian tissues has recently been reported to exist in at least two forms distinguishable by differing affinities for the inhibitory cardiac glycoside ouabain, we have studied the effects of 3,3',5-triiodo-L-thyronine (T3) treatment on these two forms of the enzyme in rat diaphragm. The inhibition of Na+-K+-ATPase activity in a crude membrane fraction by varying concentrations of ouabain conformed to a biphasic pattern consistent with the presence of two distinct isoforms with inhibition constants (KIs) for ouabain of approximately 10(-7) and 10(-4) M, respectively. Treatment of hypothyroid rats with T3 (50 micrograms/100 g body wt on 3 alternate days) nearly tripled that portion of the Na+-K+-ATPase activity corresponding to the high-ouabain-affinity form (increased by 178 +/- 24%), whereas the enzyme activity corresponding to the low-ouabain-affinity form was only slightly changed (increased by 20 +/- 5%). Measurement of the specific binding of [3H]ouabain to these membranes confirmed the presence of a class of high-affinity ouabain binding sites with a dissociation constant (Kd) of slightly less than 10(-7) M, whose maximal binding capacity was increased by T3 treatment by 185%. The calculated catalytic turnover associated with the high-affinity site was 70-80 molecules ATP hydrolyzed.site-1.s-1 and was unchanged by T3 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of lectins and tunicamycin on cAMP response to parathyroid hormone
Authors: Rizzoli R. , Bonjour J. P.
Published: December 2017

Carbohydrate moieties of cell surface glycoproteins with an external orientation play a role in hormone recognition and/or transmembrane signal transmission. We have examined the effect of various lectins, which interact with specific cell surface glycosyl residues, and of tunicamycin, an antibiotic that inhibits glycosylation of proteins, on the adenosine 3',5'-cyclic monophosphate (cAMP) response to parathyroid hormone (PTH) in confluent cultured osteoblast-like rat osteosarcoma cells (UMR-106) and opossum kidney cells (OK cells). Incubation of both cell lines with wheat germ lectin (WGL), but not with concanavalin A, succinylated wheat germ, ricin, or soybean lectins, markedly reduced the PTH-induced cAMP production, whereas the stimulation obtained with forskolin, a compound that acts directly on the adenylate cyclase enzyme, was not affected. In contrast, tunicamycin did not cause any decrease in the cAMP response to PTH. These results indicate that the masking of sialic acid residue by WGL considerably blunted PTH-stimulated cAMP production in cultured osteoblast-like and kidney cells. An 80% inhibition of glycosylation of cell surface proteins did not appear to affect the response to PTH. Thus the functional role of this carbohydrate moiety in the PTH receptor remains to be determined.
Energy expenditure during carbohydrate overfeeding in obese and nonobese adolescents
Authors: Bandini L. G. , Schoeller D. A. , Edwards J. , Young V. R. , Oh S. H. , Dietz W. H.
Published: December 2017

Basal metabolic rate (BMR), thermic effect of food (TEF), and total daily energy expenditure (TDEE) were measured in six nonobese and seven obese adolescents during periods of weight maintenance and 2 wk of carbohydrate overfeeding. BMR and TEF were measured by indirect calorimetry and TDEE by the doubly labeled water method. Fasting blood levels of insulin, thyroid, and norepinephrine (NE) and urinary excretion of NE and 4-hydroxy-3-methoxymandelic acid (VMA) were measured before and after overfeeding. Energy intake was 1.61 X BMR during maintenance and 2.45 X BMR during overfeeding. BMR increased comparably in both groups during overfeeding (obese, 7.9 +/- 1.2%, nonobese, 8.6 +/- 1.9%). TEF was similar and did not change significantly during overfeeding (maintenance: obese, 9.4 +/- 0.6%; nonobese, 9.8 +/- 0.4% vs. overfeeding: obese, 8.6 +/- 0.3%; nonobese, 9.2 +/- 0.7%). TDEE did not differ significantly between obese and nonobese. Increases in insulin and 3,5,3'-triiodothyronine levels were significant but did not differ between the two groups. Plasma NE and urinary excretion of VMA and NE did not increase during overfeeding. The thermogenic response to food or to overfeeding does not appear reduced in obese adolescents, nor does facultative thermogenesis appear to be a significant factor in weight maintenance in adolescents.
Influence of age, fat cell weight, and obesity on O2 consumption of human adipose tissue
Authors: Hallgren P. , Sjostrom L. , Hedlund H. , Lundell L. , Olbe L.
Published: December 2017

The oxygen consumption of human adipose tissue (AT) was determined in 53 adults, lean and obese, and in nine lean boys. The oxygen consumption was positively related to fat cell weight and negatively to age and degree of obesity. Men and women did not differ with respect to oxygen consumption of AT. The positive relationship between oxygen consumption per cell and fat cell size was also demonstrated in size-separated cells from the same donors. Expressed per cell the oxygen consumption was higher in fat cells from obese than in cells from lean subjects, but expressed per gram of tissue the opposite result was found. The oxygen consumption of the total AT organ was higher in obese than in lean subjects. The energy expenditure of AT constituted approximately 4% of the estimated 24-h energy expenditure in both groups. It is concluded that obese subjects do not maintain their obesity because of a reduced energy expenditure of the total AT (or of the total body). After a partial weight reduction in five subjects, the energy metabolism tended to change in direction toward the conditions seen in lean subjects. However, it is still an open question whether the observed energy metabolic aberrations of obese human AT are only secondary to the obese state or partly primary and thus of etiological importance.
Prolonged increase in insulin-stimulated glucose transport in muscle after exercise
Authors: Cartee G. D. , Young D. A. , Sleeper M. D. , Zierath J. , Wallberg-Henriksson H. , Holloszy J. O.
Published: December 2017

Exercise can induce short-term increases in the sensitivity and responsiveness of skeletal muscle glucose transport to insulin. The purpose of this study was to determine the effect of carbohydrate deprivation on the persistence of increased insulin sensitivity and responsiveness after a bout of exercise. Three hours after a bout of exercise, epitrochlearis muscles from carbohydrate-deprived (fat fed) rats showed a 25% greater increase in 3-O-methylglucose (3-MG) transport in response to a maximal insulin stimulus compared with muscles of nonexercised rats; this increase in insulin responsiveness had reversed 18 h postexercise. Muscles of rats fed carbohydrate showed no increase in insulin responsiveness 3 h after exercise. The effect of 60 microU/ml of insulin on 3-MG transport was approximately twofold greater in muscles studied 3 h after exercise than in nonexercised controls regardless of dietary carbohydrate intake. This increase in insulin sensitivity was lost within 18 h in carbohydrate-fed rats but persisted for at least 48 h in carbohydrate-deprived rats. Muscle glycogen increased approximately 41 mumol/g in the rats fed carbohydrate for 18 h, and only approximately 14.5 mumol/g in the rats fed fat for 48 h, after exercise. The persistent increase in insulin sensitivity after exercise in carbohydrate-deprived rats was unrelated to caloric intake, as muscles of fasted and fat-fed rats behaved similarly.
Impact of body fat mass and percent fat on metabolic rate and thermogenesis in men
Authors: Segal K. R. , Lacayanga I. , Dunaif A. , Gutin B. , Pi-Sunyer F. X.
Published: December 2017

To clarify further the independent relationships of body composition parameters to energy expenditure, resting metabolic rate (RMR) and postprandial thermogenesis were studied in four groups who were matched for absolute fat mass (study 1) and relative fatness (study 2). In study 1, five lean [group A, 15.4 +/- 0.6% (+/- SE) body fat] and five obese men (group B, 25.0 +/- 0.9% fat) were matched on body fat mass (13.0 +/- 0.9 vs. 14.4 +/- 0.8 kg, respectively). Fat-free mass (FFM) and total weight were greater for group A than B. RMR was measured for 3 h in the fasted state and after a 720-kcal mixed meal. RMR was greater for group A than B (1.38 +/- 0.08 vs. 1.14 +/- 0.04 kcal/min, P less than 0.05). The thermic effect of food, calculated as 3 h postprandial minus fasting RMR, was greater for group A than B (65 +/- 6 vs. 23 +/- 9 kcal/3 h; P less than 0.05). In study 2, two groups (n = 6 men/group) were matched for percent body fat (33 +/- 1% fat for both) but differed in lean, fat, and total weights: 50.8 +/- 3.1 kg FFM for the lighter (group C) vs. 68.0 +/- 2.8 kg FFM for the heavier (group D) group, P less than 0.05. RMR was lower for group C than D (1.17 +/- 0.06 vs. 1.33 +/- 0.04 kcal/min, P less than 0.05), but the thermic effect of food was not significantly different (31 +/- 3 vs. 20 +/- 6 kcal/3 h).(ABSTRACT TRUNCATED AT 250 WORDS)
Human tissue adrenergic receptors are not predictive of responses to epinephrine in vivo
Authors: Liggett S. B. , Shah S. D. , Cryer P. E.
Published: December 2017

To test the hypotheses that adrenergic receptor and adenylate cyclase characteristics of easily accessible circulating cells reflect those of relatively inaccessible extravascular catecholamine target tissues in a subtype-specific fashion and that these characteristics predict responses to catecholamines in vivo, we studied 22 normal humans. Adrenergic receptors and their linked adenylate cyclase systems were measured in mononuclear leukocytes (MNL; beta 2), platelets (alpha 2), skeletal muscle membranes (beta 2), and fat cells (B1 and alpha 2) and compared with the responses to stepped, intravenous epinephrine infusions in vivo. MNL beta 2-adrenergic receptor densities (but not antagonist affinities) were correlated (r = 0.627; P less than 0.01) with skeletal muscle beta 2-adrenergic densities. However, other adrenergic receptor characteristics and basal and maximally stimulated adenosine 3',5'-cyclic monophosphate (cAMP) contents of MNL and all adrenergic receptor characteristics and cAMP contents of platelets were unrelated to the corresponding measurements in skeletal muscle and fat. Furthermore, there were no consistent relationships between tissue adrenergic receptor-adenylate cyclase characteristics and the chronotropic, diastolic depressor, lipolytic, ketogenic, glycemic, or glycogenolytic-glycolytic responses to epinephrine in vivo. Thus the data support the hypothesis that adrenergic receptor densities on circulating cells reflect those of extravascular target tissues in a subtype-specific fashion. On the other hand, the data do not support the hypothesis that physiological interindividual variation of adrenergic receptor characteristics is of sufficient magnitude to alter sensitivity to epinephrine in vivo.
Dietary hormonal modification of growth, intestinal ATPase, and glucose transport in tilapia
Authors: Reshkin S. J. , Grover M. L. , Howerton R. D. , Grau E. G. , Ahearn G. A.
Published: December 2017

The effect of growth stimulatory and inhibitory dietary applications of hormones [3,5,3'-triiodo-L-thyronine (T3) and 17 alpha-methyltestosterone (MT)] on Na+-K+-adenosinetriphosphatase (ATPase) activity and glucose transport by upper and lower intestinal brush-border membrane vesicles of tilapia (Oreochromis mossambicus) were characterized. Both enzyme activity and glucose transport were greater in growth-stimulatory treatments and lower in growth-inhibitory treatments than in the control. Growth on stimulatory hormone treatments increased apparent glucose influx kinetics (one-half maximum glucose influx, maximum glucose influx, and apparent diffusion coefficient) in both intestinal segments, whereas inhibitory treatments reduced these parameters in upper intestine but had no effect on these parameters in lower intestine. All hormone treatments increased the stoichiometry of Na-glucose cotransport from 1:1 in the control to 2:1 under test conditions. It is suggested that observed patterns of altered growth are due, in part, to hormonally modified intestinal nutrient transport and Na+-K+-ATPase activities.