bluuebunny/crossref_metadata_2025 huggingface dataset:
LH pulsatility, biopotency, and clearance during undernutrition in orchidectomized mature rats
Authors: Dong Q. , Li B. , Rintala H. , Blair S. , Spaliviero J. , Handelsman D. J.
Published: December 2017

The effect of food restriction on circulating luteinizing hormone (LH) levels in orchidectomized rats is controversial. The present study demonstrates that decreasing food intake by 50% for 3-10 days in orchidectomized rats increases LH pulse amplitude, length, area under pulse curve, and mean levels but decreases LH pulse frequency compared with ad-lib fed, orchidectomized controls. The effects on pulsatile LH secretion of food reduction by 50% with or without dilution by cellulose to maintain food volume in orchidectomized rats were also examined. Food volume influences pulsatile LH secretion independent of macronutrient effect after 3 days of food restriction, but subsequently macronutrient deprivation predominates. The exaggerated increase in LH levels in orchidectomized rats subject to food restriction for 7 days was not due to immunochemical or chromatographic heterogeneity or alteration in biopotency of circulating LH molecules. Intravenously injected 125I-labeled rat LH analyzed by noncompartmental modeling revealed that neither LH clearance nor mean residence time was reduced by food restriction. We conclude that during food restriction in orchidectomized rats, increases in LH pulse amplitude exceed and precede the decreases in LH pulse frequency, although the early changes in pulse amplitude are predominantly due to reduced food volume rather than macronutrient deprivation.
Involvement of epidermal growth factor in inducing obesity in ovariectomized mice
Authors: Kurachi H. , Adachi H. , Ohtsuka S. , Morishige K. , Amemiya K. , Keno Y. , Shimomura I. , Tokunaga K. , Miyake A. , Matsuzawa Y. , et al.
Published: December 2017

Ovariectomy (Ovx) of mice significantly increases the epidermal growth factor (EGF) concentration in the submandibular gland. To elucidate the role of this elevated EGF in obesity of Ovx mice, we examined the effects of sialoadenectomy (Sx) and anti-EGF rabbit antiserum administration on the body weight (BW) gain and carcass fat deposition in Ovx animals. Studies were performed in four groups of mice consisting of control, Ovx, Ovx+Sx, and Ovx+anti-EGF groups. Ovx increased the BW gain compared with the control animals, whereas Sx and anti-EGF significantly reduced it. Although the relative weights (weight ratio to BW) of the liver and kidney were not significantly changed by Ovx, Sx, or anti-EGF treatment of Ovx mice, the relative weights of mesenteric, parametrial, and subcutaneous fat tissues were increased in Ovx mice, and this increase was significantly reduced by Sx or anti-EGF administration. Ovx induced adipocyte hypertrophy, and this effect was eliminated by Sx and anti-EGF. Moreover, acyl-CoA synthetase mRNA level was increased by Ovx, and this increase was reduced by Sx and anti-EGF in mesenteric fat tissue. These findings suggest that elevation of EGF may play a role in the induction of obesity in Ovx mice.
Second messenger signaling of PTH- and PTHRP-stimulated osteoclast-like cell formation from hemopoietic blast cells
Authors: Sugimoto T. , Kanatani M. , Kaji H. , Yamaguchi T. , Fukase M. , Chihara K.
Published: December 2017

The second messenger signaling mechanisms of parathyroid hormone (PTH)- and PTH-related peptide (PTHRP)-stimulated osteoclast-like cell formation were investigated in mouse hemopoietic blast cells that possessed PTH binding sites. Human (h) PTH-(1-34) or hPTHRP-(1-34) resulted in a dose-dependent stimulation of tartrate-resistant acid phosphatase-positive multinucleated cells (MNC) formation. Pretreatment with [Nle8,18Tyr34]hPTH-(3-34) significantly blocked hPTH-(1-34)- and hPTHRP-(1-34)-stimulated MNC formation. Dibutyryladenosine 3',5'-cyclic monophosphate (10(-4) M) and forskolin (10(-5) M) as well as the stimulatory diastereoisomer of adenosine 3',5'-cyclic phosphorothioate (Sp-cAMPS), a direct activator of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) (10(-4) M), stimulated MNC formation, and Rp-cAMPS, an inhibitor of PKA activation (10(-4) M), almost completely inhibited MNC formation stimulated by the aforementioned agents but not by 1,25-dihydroxyvitamin D3. Moreover, Rp-cAMPS significantly blocked PTH- and PTHRP-stimulated MNC formation. Treatment with calcium ionophores (10(-8) and 10(-7) M) and phorbol 12-myristate 13-acetate, a protein kinase C (PKC) activator (10(-8) to 10(-6) M), but not 4 alpha-phorbol 12,13-didecanoate, a phorbol incapable of activating PKC, stimulated MNC formation. Two PKC inhibitors [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride and staurosporine] equally blocked PTH- and PTHRP-stimulated MNC formation. The combined pretreatment with Rp-cAMPS and PKC inhibitors completely blocked PTH- and PTHRP-stimulated MNC formation. Present findings indicate that the activation of PKA and PKC is directly linked to PTH- and PTHRP-stimulated osteoclast-like cell formation from hemopoietic blast cells.
Effects of exercise training on muscle GLUT-4 protein content and translocation in obese Zucker rats
Authors: Brozinick J. T. , Etgen G. J. , Yaspelkis B. B. , Kang H. Y. , Ivy J. L.
Published: December 2017

The rates of muscle glucose uptake of trained (TR) and untrained (UT) obese Zucker rats were assessed by hindlimb perfusion under basal conditions (no insulin) in the presence of a maximally stimulating concentration of insulin (10 mU/ml) and after muscle contraction elicited by electrical stimulation of the sciatic nerve. Perfusate contained 28 mM glucose and 7.5 microCi/mmol of 2-deoxy-D-[3H]glucose. Muscle GLUT-4 concentration was determined by Western blot analysis and expressed as a percentage of a heart standard. The rates of insulin-stimulated glucose uptake were significantly higher in the plantaris, red gastrocnemius (RG), and white gastrocnemius (WG), but not the soleus or extensor digatorum longus (EDL) of TR compared with UT rats. After muscle contraction the rates of glucose uptake in the TR rats were significantly higher in the soleus, plantaris, and RG. TR rats had significantly higher GLUT-4 protein concentration and citrate synthase activity than the UT rats in the soleus, plantaris, RG, and WG. Basal plasma membrane GLUT-4 protein concentration of TR rats was 144% above UT rats (P < 0.01). Stimulation by insulin and contraction resulted in a significant increase in plasma membrane GLUT-4 protein concentration in UT rats only. However, plasma membrane GLUT-4 protein concentration in insulin- and contraction-stimulated TR rats remained 53% and 30% greater than that of UT rats, respectively (P < 0.05). Exercise training did not alter basal, insulin-, or contraction-stimulated GLUT-4 functional activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunolocalization of GLUT-1 glucose transporter in rat skeletal muscle and in normal and hypoxic cardiac tissue
Authors: Doria-Medina C. L. , Lund D. D. , Pasley A. , Sandra A. , Sivitz W. I.
Published: December 2017

We compared the expression and cell-type localization of GLUT-1 mRNA and protein between cardiac and skeletal muscle of normal rats. Also, since we recently showed that cardiac GLUT-1 is upregulated in rats exposed to hypobaric hypoxia, we examined the cellular localization of GLUT-1 in cardiac tissue of normal and hypoxic rats. Confocal light microscopy and double immunofluorescent labeling revealed intense localization of GLUT-1 around neurofilament immunoreactivity within gastrocnemius muscle consistent with the previously described localization of large amounts of GLUT-1 in perineurial sheaths of skeletal muscle. However, using the same methods, we were unable to visualize GLUT-1 adjacent to nerve fibers in numerous sections of right or left ventricles or atria. Compared with skeletal myoctes, however, GLUT-1 immunofluorescence among cardiomyocytes was much more intense, particularly along the plasma membrane and especially intercalated discs. GLUT-1 immunofluorescence was also seen within the walls of arterioles within the heart. The predominant localization of GLUT-1 expression to cardiomyocytes in heart tissue was confirmed by in situ mRNA hybridization to digoxigenin-conjugated GLUT-1 cDNA. Northern blot analysis demonstrated that GLUT-1 mRNA was increased severalfold in the cardiac tissues compared with skeletal muscle. Although we detected GLUT-1 protein by immunoblotting of detergent extracts of the heart, we could not detect GLUT-1 in similar extracts of skeletal muscle. The cell type distribution of GLUT-1 in hearts of hypoxic rats was not different by immunohistochemistry from normals. These data indicate that 1) the cell-type distribution of GLUT-1 in the heart differs markedly from that in skeletal muscle. GLUT-1 in cardiac tissue, unlike skeletal muscle, is predominantly expressed within myocytes. 2) Cardiac GLUT-1 is not located along nerve fibers. 3) GLUT-1 mRNA and protein levels in cardiac tissue are considerably greater than in skeletal muscle. 4) The hypoxia-induced increase in cardiac GLUT-1 that we previously reported must occur within cardiomyocytes.
Atrial natriuretic peptides are present throughout the plant kingdom and enhance solute flow in plants
Authors: Vesely D. L. , Gower W. R. , Giordano A. T.
Published: December 2017

The present investigation was designed to 1) determine if atrial natriuretic-like peptides are present throughout the plant kingdom and 2) to determine if these peptides increase the flow of solute and/or water upward to leaves and flowers of plants. The 126-amino acid prohormone of atrial natriuretic factor (proANF)-(1-30), proANF-(31-67), and atrial natriuretic factor (ANF)-like peptides were present in the roots, stems, leaves, and flower petals of the more highly developed plants (Tracheophyta), with their highest concentrations being: Florida beauty > buddhist pine > Boston fern > rose = geranium = resurrection plant or club moss > Moses-in-the-cradle > Florida coontie. These peptides were also present in Bryophata (plants without vascular tissue or roots) and even in Euglena, flagellated chlorophyll-containing plants without leaves, stems, or roots. proANF-(1-30), proANF-(31-67), and proANF-(79-98) but not ANF (each at < 5.9 pg/ml) significantly increased (P < 0.001) the flow of colored water up stems, coloring their flowers 15-35 min earlier than the other one-half of the same flowers without exogenous peptide addition. These same peptides increased the rate of transpiration (i.e., loss of water from the leaves) and the absorption of solutions. High-performance gel permeation chromatography revealed that proANF-(1-30), proANF-(31-67), and ANF extracted from plants are very similar to their pure synthetic human sequences, with elution profiles and molecular weights of the plant extracts duplicating those of the pure synthetic peptides.
Alanine umbilical uptake, disposal rate, and decarboxylation rate in the fetal lamb
Authors: Guyton T. S. , De Wilt H. , Fennessey P. V. , Meschia G. , Wilkening R. B. , Battaglia F. C.
Published: December 2017

Fetal plasma alanine disposal rate (DR) and decarboxylation rate were measured at 132 +/- 1 days gestation in nine fetal lambs infused with L-[1-14C]alanine via a brachial vein. In five experiments, L-[1-13C]alanine was added to the infusate. Using L-[1-14C]alanine, we found mean DR to be 15.5 +/- 1.8 mumol.min-1 . kg-1. DR was significantly correlated to both arterial plasma alanine and whole blood lactate concentrations. Placental uptake of fetal plasma alanine accounted for 19 +/- 4% of DR. Fetal and placental production of CO2 from the first carbon of alanine were 61 +/- 2 and 16 +/- 2% of DR, respectively, for a total uterine excretion of 77 +/- 3%. Net alanine flux from placenta to fetus was 5.2 +/- 0.5 mumol.min-1 x kg-1, which was less than fetal plasma alanine decarboxylation (9.4 +/- 1.2 mumol.min-1 x kg-1) plus fetal alanine accretion (2.4 mumol.min-1 x kg-1). Utilizing L-[1-13C]alanine, we found DR to be 14.2 +/- 0.8 mumol.min-1 x kg-1, not significantly different from the 14C data. We conclude that both the umbilical uptake of alanine from the placenta and fetal alanine synthesis contribute to fetal alanine supply and that oxidation is the main route of fetal plasma alanine disposal.
Interaction of PDGF and natriuretic peptides on mesangial cell proliferation and endothelin secretion
Authors: Kohno M. , Ikeda M. , Johchi M. , Horio T. , Yasunari K. , Kurihara N. , Takeda T.
Published: December 2017

The present study examined the possible interaction of platelet-derived growth factor (PDGF) and atrial or brain natriuretic peptides (ANP and BNP, respectively) on cellular proliferation and secretion of endothelin-1 in cultured rat mesangial cells. PDGF increased cellular proliferation and endothelin-1 secretion. The protein kinase C (PKC) inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, staurosporine, and PKC inhibitor peptide, inhibited such stimulation. Rat ANP-(1-28) and rat BNP-45 exhibited clearly dose-related inhibition of PDGF-stimulated cellular proliferation and endothelin-1 secretion. This inhibition by ANP and BNP was paralleled by an increase in the cellular level of guanosine 3',5'-cyclic monophosphate (cGMP). Results indicate that PDGF stimulates cellular proliferation and endothelin-1 secretion in cultured rat mesangial cells by a mechanism probably involving activation of PKC and that ANP and BNP inhibit such stimulation through a cGMP-dependent process.
Insulin-like growth factor and growth hormone receptor in nephrotic rats
Authors: Thabet M. A. , Challa A. , Chan W. , Liu F. , Hintz R. L. , Chan J. C.
Published: December 2017

In an attempt to elucidate the mechanism of growth retardation in the nephrotic syndrome, specific serum and hepatic growth factors were measured in Sprague-Dawley rats in which nephrotic syndrome was produced by administration of puromycin (1.5 mg.100 g body wt-1.day-1) for 12 days. On the 13th day, the results of these nephrotic animals were compared with those of an equal number of pair-fed and control animals: the mean dietary intake of the nephrotic group was 71% that of the control group (P < 0.001). Serum insulin-like growth factor (IGF) binding protein-3 was significantly reduced (P < 0.005) in the nephrotic rats, compared with the pair-fed and the control groups. Hepatic IGF-I mRNA in the nephrotic rats averaged 36% that of control (P < 0.001) and 46% that of the pair-fed animals (P < 0.001). Hepatic growth hormone receptor (GHr) mRNA in the nephrotic rats averaged 19% of that of the control (P < 0.001) and 27% of that of the pair-fed rats (P < 0.001). These results indicate that the growth retardation of the nephrotic rats may be associated with the significant decrease in IGF-I mRNA and reduction in GHr mRNA.
Vasopressin V1 and V2 receptors in diabetes mellitus
Authors: Trinder D. , Phillips P. A. , Stephenson J. M. , Risvanis J. , Aminian A. , Adam W. , Cooper M. , Johnston C. I.
Published: December 2017

Diabetes mellitus causes hypertonicity, increased plasma arginine vasopressin (AVP), polydipsia, and polyuria. Downregulation of AVP V2 receptors may contribute to the polyuria through diminished V2 receptor-mediated free water retention. After 2 wk of streptozotocin-induced diabetes mellitus, the diabetic rats had raised plasma glucose, AVP, and osmolality levels (P < 0.001) compared with nondiabetic controls (Sham). Insulin treatment (4 U long-acting insulin sc, daily) partially lowered these values (P < 0.01). There was a reduction in the number of renal and hepatic V1 receptors in the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The receptor affinity remained unchanged. In parallel, there was a reduction in maximum AVP-activated total inositol phosphate production in the liver and kidney of the diabetic and diabetic+insulin animals compared with the sham animals (P < 0.05). The density and affinity of renal V2 receptors and AVP-stimulated adenosine 3',5'-cyclic monophosphate production in the diabetic and diabetic+insulin animals were unchanged compared with the sham. These results demonstrate differential regulation of AVP receptors and suggest that downregulation of renal V2 receptors does not contribute to the polyuria of diabetes. In contrast, downregulation of V1 receptors might contribute to diminished V1 receptor-mediated biological responses to AVP seen in diabetes mellitus.
Regulation of fatty acid movement in human adipose tissue in the postabsorptive-to-postprandial transition
Authors: Frayn K. N. , Shadid S. , Hamlani R. , Humphreys S. M. , Clark M. L. , Fielding B. A. , Boland O. , Coppack S. W.
Published: December 2017

There is net outward flow of fatty acids from adipose tissue in the fasted state but net inward flow and storage in the postprandial state. We investigated how this is regulated. Arteriovenous differences were measured across a subcutaneous adipose depot in six normal subjects before and for 5 h after a meal containing 80 g fat and 80 g carbohydrate. In five further experiments, insulin was infused at 40 mU.m-2.min-1 from 30 min after the meal, clamping the plasma glucose. Net transcapillary fatty acid flow changed from negative (outward flow from tissue to capillaries) in the postabsorptive state to consistently positive (net inward flow, implying fat storage) after the meal despite continued net efflux of fatty acids into venous blood. In the "clamped" experiments (with additional insulin), net fatty acid efflux in the venous blood was suppressed and positive transcapillary flux (storage) was more marked. Regulation of fatty acid flow appeared to depend on coordinated changes in hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL) action and fatty acid esterification. Additional insulin caused no further suppression of HSL or activation of LPL but markedly stimulated fatty acid retention (presumed to represent esterification). In the absence of additional insulin, a high proportion of the fatty acids liberated by LPL are released into the venous plasma in both postabsorptive and postprandial states. We hypothesize that this "loss" of fatty acids is necessary to give precise control to the pathway of fat storage.
Insulin increases a biochemically distinct pool of diacylglycerol in the rat soleus muscle
Authors: Chen K. S. , Heydrick S. J. , Brown M. L. , Friel J. C. , Ruderman N. B.
Published: December 2017

Insulin stimulates the incorporation of glucose-carbon into diacylglycerol (DAG) in rat skeletal muscle, and its ability to do so is enhanced severalfold after the muscle is denervated (S. J. Heydrick, N. B. Ruderman, T. J. Kurowski, H. A. Adams, and K. S. Chen. Diabetes 40: 1707-1711, 1991). The present studies were carried out to assess the nature of this newly synthesized DAG and to identify factors other than insulin that determine its rate of appearance in the incubated rat soleus muscle. In control muscles, incubated at a medium glucose concentration of 6-7.5 mM, insulin (10 mU/ml) increased DAG content (mass) by 20-25% and increased the incorporation of a 14C label from extracellular [14C]glucose into DAG by 200-300%. The labeling of DAG reached a plateau within 20 min, at which time the labeled DAG comprised a very small percentage of total muscle DAG. Molecular species analysis revealed that DAG species having fatty acids of 18:2/20:4 and 18:2/18:2 each constituted approximately 2% of total DAG content but contained 20 and 15%, respectively, of the glucose-derived label in DAG. In contrast, 16:0/18:1 accounted for > 80% of total DAG content but only 18% of the total label incorporated into DAG. Insulin did not alter this pattern. Denervation also did not alter the molecular species profiles of the labeled DAGs or DAG analyzed by mass. An increased incorporation of glucose-carbon into DAG was observed in muscles incubated with 30 mM glucose in place of the usual 7.5-mM concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
IGF-I mediates the stimulatory effect of high calcium concentration on osteoblastic cell proliferation
Authors: Sugimoto T. , Kanatani M. , Kano J. , Kobayashi T. , Yamaguchi T. , Fukase M. , Chihara K.
Published: December 2017

Since our recent study revealed that an increase in extracellular calcium ([Ca2+]e) but not magnesium enormously stimulated DNA synthesis in osteoblastic MC3T3-E1 cells at the minimal and maximal effective concentration of 3 and 5 mM, respectively, the present study was performed to clarify how an increase in [Ca2+]e caused a stimulation of DNA synthesis of these cells. Neither calcium channel blockers (verapamil, diltiazem, and nifedipine) and dantrolene, an inhibitor of Ca release from intracellular Ca pool, nor indomethacin, an inhibitor of prostaglandin synthesis, affected the high [Ca2+]e-induced increase in DNA synthesis. DNA synthesis first increased after a 12-h exposure to 5 mM [Ca2+]e, and cycloheximide eliminated the stimulatory effect of high [Ca2+]e on DNA synthesis, suggesting that this stimulatory effect of high [Ca2+]e was dependent on new protein synthesis. There is recent evidence that MC3T3-E1 cells constitutively produce and secrete insulin-like growth factor I (IGF-I) and possess IGF-I receptors. IGF-I antiserum (1:10,000 to 1:100) blocked the high [Ca2+]e-induced increase in DNA synthesis in a concentration-dependent manner. A neutralizing abolished DNA synthesis stimulated by high [Ca2+]e, indicating that IGF-I mediated the high [Ca2+]e-induced effect. Furthermore, high [Ca2+]e significantly increased the secretion of immunoreactive IGF-I into the medium as well as the expression of IGF-I mRNA. Present findings indicate that an increase in [Ca2+]e stimulated DNA synthesis of osteoblasts through the mechanism of an increase in the production and secretion of IGF-I.
Splanchnic and systemic absorption of intraperitoneal insulin using a new double-tracer method
Authors: Radziuk J. , Pye S. , Seigler D. E. , Skyler J. S. , Offord R. , Davies G.
Published: December 2017

The absorption of a bolus of intraperitoneal insulin into the splanchnic and peripheral circulations was separately assessed in dogs using an infusion of two insulin tracers (A1-[3H]insulin and B1-[3H]insulin). One tracer was infused into the superior mesenteric artery and the second into the jugular vein. Serial samples were taken before and after an injection of insulin (1 U/kg ip). Sampling was from the portal vein and the inferior vena cava. By using the principle of equivalent entry of tracer and unlabeled material, we developed two simultaneous equations for the rate of splanchnic and peripheral insulin absorption at each time point. These were solved to yield the two rates. Mean concentrations in the portal vein were approximately 25% higher than in the inferior vena cava, reflecting the splanchnic absorption. This rate accounted for almost half (51 +/- 9%) of the insulin absorbed. The remainder of the absorption was peripheral. The total recovery of intraperitoneal insulin, absorbed by either route, was 88 +/- 11%. Portal absorption peaked earlier than peripheral. Absorption by both routes was 90% complete within approximately 2 h (131 +/- 16 min). In summary, therefore, intraperitoneal insulin is rapidly and almost completely absorbed, with absorption split between the splanchnic and peripheral routes of entry.
Thermogenic, hormonal, and metabolic effects of a TPN mixture. Influence of glucose and amino acids
Authors: Carlson G. L. , Gray P. , Arnold J. , Little R. A. , Irving M. H.
Published: December 2017

The thermogenic, hormonal, and metabolic effects of intravenous nutrition were examined by administering a complete total parenteral nutrition (TPN) mixture to 11 subjects, and the relative contributions of the glucose and amino acid components of the mixture were evaluated by administering these nutrients separately (n = 7 and n = 6, respectively). The complete TPN mixture caused a 22.9% rise in resting energy expenditure (REE), which significantly exceeded that associated with glucose (10.4% P < 0.02). The rise in REE produced by the amino acids (11.5%) did not differ significantly from that associated with administration of the TPN or glucose. The rise in REE associated with the TPN was almost exactly equal to the sum of the rises associated with the separate components of the mixture (22.9% and 22.0%, respectively), indicating that glucose and amino acids contributed equally to the thermogenic effect of the TPN mixture. In contrast, although the amino acid component of the TPN mixture was associated with small but significant reductions in plasma free fatty acid and glycerol concentration and with small increases in plasma insulin concentration, the effects of the complete TPN mixture were significantly greater and attributable to the glucose component.
Effects of estrogen on free fatty acid metabolism in humans
Authors: Jensen M. D. , Martin M. L. , Cryer P. E. , Roust L. R.
Published: December 2017

To determine whether estrogen directly affects effective adipose lipolysis, palmitate rate of appearances ([14C]palmitate) was measured in 15 postmenopausal women. Each volunteer was studied after > or = 2 mo of estrogen treatment and again after > or = 2 mo of estrogen deficiency. Plasma hormone concentrations were controlled and identical on the 2 study days with use of the pancreatic clamp technique, and the lipolytic response to epinephrine and epinephrine + phentolamine was assessed. Results showed that overall palmitate flux was greater (10-20%, P < 0.05) during the estrogen-deficient than during the estrogen-replete study. Adrenergic stimulation of lipolysis was not specifically influenced by estrogen treatment, and control of plasma hormone concentrations did not eliminate the difference in palmitate flux between the estrogen-deficient and estrogen-replete study days. We conclude that estrogen deficiency is associated with increased plasma free fatty acid availability and that estrogen likely has direct, albeit small, effects on adipose tissue lipolysis.
Sleep endocrine effects of antigluco- and antimineralocorticoids in healthy males
Authors: Wiedemann K. , Lauer C. , Pollmacher T. , Holsboer F.
Published: December 2017

In several mammalian species the responsiveness of brain neurons to corticosteroids is mediated by mineralo- (MR) and glucocorticoid (GR) receptors. These receptors play a key role not only in the endocrine adaptation to stress but also in corticosteroid-induced changes of behavior, including sleep. We further explored the specific physiological role of this binary receptor system in the human brain by studying electroencephalogram (EEG) sleep and changes in plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, and growth hormone from 1800 to 0700 h in a series of investigations in healthy men pretreated the previous evening with the nonselective GR agonist dexamethasone (Dex) and then receiving at 1400 h either placebo, spironolactone (Spi), an MR antagonist, or mifepristone (Mif), a GR antagonist. The Dex-induced suppression of ACTH and cortisol was unaltered after Spi (200 mg) but attenuated by Mif treatment (400 mg). The sleep-associated plasma growth hormone surge was increased by Dex, an effect that remained unchanged by Spi but was reduced by Mif treatment. Pretreatment with Dex did not by itself induce recognizable effects on EEG sleep, but the Dex combination with Spi reduced the amount of rapid-eye-movement (REM) sleep. With Dex plus Mif, both REM sleep and slow wave sleep (SWS) were reduced compared with placebo. The Dex-induced endocrine effects on plasma ACTH, cortisol, and growth hormone concentrations could not be antagonized by Spi, which acts via MRs mainly located in the hippocampus, but were compensated for in part by Mif, which antagonizes GR at the pituitary and in the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)
Indomethacin has distinct early and late actions on bone formation induced by mechanical stimulation
Authors: Chow J. W. , Chambers T. J.
Published: December 2017

The capacity of bone to adapt its architecture in response to changing mechanical demands is well recognized. However, the mechanisms by which mechanical stimuli are translated into new bone formation are poorly understood. Prostaglandins (PGs) may play a role. We therefore tested the effect of indomethacin on the cancellous bone formation induced by mechanical stimulation in the 8th caudal vertebrae of adult rats. Rats were given indomethacin 3 h before loading, 3 h before loading and daily thereafter, 6 h after loading, or 6 h after loading and daily thereafter. The increase in bone formation caused by loading was suppressed by a single dose of indomethacin if given before but not after loading. Daily administration of indomethacin suppressed the mechanical response, even when started after loading. These results suggest that PGs are essential for the transduction of mechanical stimuli into bone formation, and also that there may be two distinct phases of PG dependency in the response of bone to mechanical loading: an early phase associated with the immediate loading period and a later phase associated with osteogenic interactions entrained by the early phase.
Beta-adrenergic stimulation of energy expenditure and forearm skeletal muscle metabolism in lean and obese men
Authors: Blaak E. E. , Van Baak M. A. , Kemerink G. J. , Pakbiers M. T. , Heidendal G. A. , Saris W. H.
Published: December 2017

The effect of beta-adrenergic stimulation on whole body energy expenditure and forearm skeletal muscle metabolism was investigated in lean and obese men. Whole body energy expenditure was determined during rest and during intravenous infusion of increasing doses of the nonselective beta-agonist isoprenaline (Iso). Forearm skeletal muscle metabolism was investigated with Iso infusion with and without simultaneous infusion of the beta 1-blocker atenolol (AT) by measuring skeletal muscle blood flow (SMBF) and arteriovenous concentration differences of various metabolites. The changes in SMBF were estimated from forearm total (venous occlusion plethysmography), skin (laser doppler), and fat tissue blood flow (133Xe washout). The increase in whole body energy expenditure with Iso was similar in lean and obese subjects. With Iso, the rise in arterial or arterialized glycerol and nonesterified fatty acids (NEFA) was lower in obese than lean subjects, which may reflect a lower beta-adrenergically mediated lipolysis in obesity. During infusion of increasing doses of Iso, the respiratory exchange ratio decreased significantly in lean subjects but not in the obese subjects, which indicates a more pronounced increase in fat oxidation in lean subjects. This is confirmed by the data on skeletal muscle metabolism, where NEFA uptake was increased in lean subjects, whereas the obese subjects showed a tendency toward an increased glucose uptake and a significantly increased lactate release. With Iso plus AT (mainly beta 2-adrenergic stimulation), both groups showed an increased skeletal muscle lactate release. In conclusion, although the thermogenic response to Iso was similar in lean and obese subjects, the utilization of fat seems to be impaired in obesity.
Inhibition of pancreatic proglucagon gene expression in mice bearing subcutaneous endocrine tumors
Authors: Ehrlich P. , Tucker D. , Asa S. L. , Brubaker P. L. , Drucker D. J.
Published: December 2017

The proglucagon-derived peptides (PGDPs) play key roles in the regulation of carbohydrate metabolism and insulin secretion, yet the factors important for the regulation of proglucagon gene expression remain poorly understood. Recent experiments demonstrated that nude mice carrying subcutaneous proglucagon-SV40 T antigen tumors contained markedly reduced levels of the pancreatic PGDPs. To determine if elevated circulating levels of the PGDPs are consistently associated with inhibition of endogenous pancreatic proglucagon gene expression, we have now studied islet hormone gene expression in mice bearing three different endocrine tumors (InR1-G9, RIN1056A, and STC-1) that express the proglucagon gene. All tumors synthesized large amounts of the PGDPs. Plasma levels of the PGDPs were elevated in all tumor-bearing mice (8- to 22-fold greater than controls, P < 0.001), and this was associated with marked inhibition of mouse pancreatic proglucagon gene expression. The levels of pancreatic PGDPs were also significantly lower in tumor-bearing mice compared with controls (71 +/- 4, 38 +/- 6, and 18 +/- 2% of controls for InR1-G9-, RIN1056A-, and STC-1-bearing mice, respectively, P < 0.05-0.001). This inhibition of proglucagon gene expression was highly specific, in that no consistent change in pancreatic insulin or somatostatin gene expression was detected. Examination of proglucagon posttranslational processing in the tumors demonstrated that proglucagon was processed differently in each tumor to yield a unique profile of PGDPs. These observations demonstrate that elevated circulating levels of the PGDPs are associated with reduction in islet size and inhibition of proglucagon gene expression and PGDP synthesis in the pancreatic A cell.
Effects of energy restriction on acute adrenoceptor and metabolic responses to exercise in obese subjects
Authors: Kempen K. P. , Saris W. H. , Senden J. M. , Menheere P. P. , Blaak E. E. , van Baak M. A.
Published: December 2017

This study was intended to investigate the effects of energy restriction on the acute responses of platelet alpha 2- and lymphocyte beta 2-adrenoceptors to exercise in obese female subjects. Seven obese females were restricted to a low-energy formula diet (2.0 MJ/day) for 4 wk. As result of the diet, there was a 7.8-kg weight loss. No significant changes could be detected in sleeping and resting metabolic rate expressed per kilogram fat-free mass. Basal venous glucose, insulin, and norepinephrine levels decreased as a result of the diet, whereas free fatty acid values increased. Before the diet, 60 min of exercise (45% peak mechanical power) caused no alteration in the density of lymphocyte beta 2-adrenoceptors. At the end of 4 wk of dieting, the density was significantly increased in response to exercise, together with a higher thermogenic and lipolytic response and decreased venous insulin levels. Energy restriction resulted in an increased basal platelet alpha 2-adrenoceptor density, whereas exercise did not modify density and affinity of platelet alpha 2-adrenoceptors. The results indicate that adrenoceptor numbers can be modulated by energy restriction in obesity. Modulation of adrenoceptor density may play a role in increased exercise-induced lipolysis during energy restriction.
Metabolic regulation of intracellular calcium concentration in mouse pancreatic islets of Langerhans
Authors: Nadal A. , Valdeolmillos M. , Soria B.
Published: December 2017

Intracellular Ca2+ concentration ([Ca2+]i) handling during K(+)-induced Ca2+ loads was studied in single islets of Langerhans. K(+)-induced depolarization caused a rapid and transient rise in [Ca2+]i. After K+ removal [Ca2+]i declined with a time course usually fitted by the sum of two exponential functions. Partial Na+ removal increased the resting [Ca2+]i level, indicating the existence of a Na+/Ca2+ exchange, but only slightly impaired the recovery from Ca2+ loads. Metabolic poisoning with CN- increased the resting Ca2+ level and slowed down the recovery from Ca2+ loads. Removal of external Na+ in islets poisoned with CN- strongly inhibited Ca2+ removal mechanisms. An increase in the glucose concentration from 0 to 16 mM (in the presence of diazoxide) resulted in a decrease in the resting [Ca2+]i and an acceleration of [Ca2+]i recovery from K+ loads. These results suggest that the main mechanism responsible for Ca2+ homeostasis is dependent on metabolic energy and that such energy can be provided by glucose metabolism.
Metabolic interactions between surplus dietary energy intake and cigarette smoking or its cessation
Authors: Neese R. A. , Benowitz N. L. , Hoh R. , Faix D. , LaBua A. , Pun K. , Hellerstein M. K.
Published: December 2017

Cigarette smoking (CS) alters lipid metabolism and is associated clinically with an atherogenic lipid profile. We recently showed that, under controlled eucaloric dietary conditions, CS stimulates lipolysis without increasing oxidation of fat and that cessation of CS does not result in a rebound tendency to synthesize or store fat. We asked here whether the ad libitum intake of surplus dietary energy interacts with the metabolic effects of CS or its cessation. Eight male heavy smokers were allowed ad libitum food intake in a metabolic ward, 1 wk in CS phase and 1 wk in non-CS phase, followed by 4 wk of outpatient non-CS and a repeat 7-day study. De novo hepatic lipogenesis (DNL), lipolysis, substrate cycling of free fatty acids (FFA), hepatic glucose production, and energy expenditure were measured by using a multiple stable-isotope infusion protocol and indirect calorimetry. Surplus dietary energy intake (> 150% of predicted energy needs) occurred in five of eight subjects (2 subjs > 5,500 kcal/day, 3 subjs > 4,000 kcal/day) with weight gain of 1–4 kg/wk, but with no difference between CS and non-CS phases. Acute CS significantly increased (P < 0.05) serum FFA concentrations (58%), FFA flux (63%), and glycerol flux (36%); nonsignificantly increased extra-adipocyte (hepatic) esterification of FFA (125%, P = 0.10) and resting energy expenditure (4.1%, P = 0.22); and did not change adipocyte reesterification of FFA or whole body oxidation of fat. Basal metabolic parameters (after overnight abstention from CS) did not differ between phases. Fractional DNL correlated significantly with excess energy intake (r2 = 0.39) and with percentage of total energy needs provided by carbohydrate (r2 = 0.47). The absence or presence of CS did not affect the increase in fractional DNL in subjects with excess energy intake, however. We conclude that cessation of CS does not result in a rebound tendency to synthesis or storage of fat, even in the presence of positive short-term energy balance, contrary to previous suggestions. Moreover, stimulation of lipolysis by CS does not increase oxidation of fat and thereby protect against fat deposition under conditions of surplus energy intake. The prevention of weight gain after cessation of CS, whether or not nicotine is provided, should focus on energy balance (calorigenesis as well as intake) rather than specific alterations in lipid metabolism.
Effects of epinephrine infusion on muscle glycogenolysis during intense aerobic exercise
Authors: Chesley A. , Hultman E. , Spriet L. L.
Published: December 2017

The purpose of this study was to determine whether an epinephrine (Epi) infusion would enhance muscle glycogenolysis during intense aerobic exercise. Epi was infused at rates that produced the same plasma Epi concentrations observed after caffeine (Caf) ingestion. Seven male subjects cycled for 15 min at 80% maximal O2 uptake during four different trials. Trial 1 was preceded by a 9 mg/kg oral dose of Caf to determine resting and exercise plasma Epi concentrations. Trial 2 was used to determine the Epi infusion rates needed to mimic the plasma Epi levels found with Caf. Trials 3 and 4 were randomized and consisted of either an Epi infusion or a saline infusion (control, Con). During Epi and Con trials muscle samples were obtained from the vastus lateralis at 0, 3, and 15 min of exercise. Plasma Epi levels were similar between Caf and Epi and were elevated twofold compared with Con. At 5 min of exercise the plasma Epi concentrations were 1.51 +/- 0.26, 2.61 +/- 0.34, and 2.97 +/- 0.45 nM for the Con, Caf, and Epi trials, respectively. Plasma Epi increased to 3.08 +/- 0.56, 5.45 +/- 1.11, and 5.86 +/- 1.03 nM at 14 min of exercise in the Con, Caf, and Epi trials, respectively. Muscle glycogenolysis was not different between trials (Con 220.5 +/- 25.3 vs. Epi 240.6 +/- 12.1 mmol/kg dry muscle). In addition, the degradation of muscle ATP and phosphocreatine and the accumulation of muscle lactate, ADP, and AMP were similar between trials.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of corticosteroids on free and sulfoconjugated catecholamines at birth in premature newborn sheep
Authors: Stein H. M. , Martinez A. , Oyama K. , Blount L. , Padbury J. F.
Published: December 2017

We previously demonstrated that prenatal corticosteroids attenuated the expected exponential increase in circulating catecholamines at birth. The present studies were undertaken to determine if alteration in sulfoconjugation could account for this attenuation. Catheterized fetal lambs received saline (n = 6) or corticosteroids (n = 8) intravenously for 60 h. The lambs were delivered by cesarean section at 130 +/- 1 days gestation. Ventilatory and cardiovascular responses and plasma catecholamine concentrations were measured for 2 h after birth. Although plasma free catecholamines levels were higher in controls than in corticosteroid-treated fetuses, the sulfoconjugated levels were similar in the two groups. Thus the corticosteroid-treated fetuses had a higher proportion of plasma sulfoconjugated catecholamines consistent with the possibility that sulfoconjugation was augmented during intrauterine life. After birth, the corticosteroid-treated animals showed an attenuated increase in plasma free catecholamine levels compared with controls but a similar increase in sulfoconjugated catecholamine levels to the control animals. The proportion of plasma sulfoconjugated catecholamines was higher in the corticosteroid-treated animals; however, the increase in sulfoconjugated catecholamines was insufficient to account for the attenuated overall increase in total catecholamines in the corticosteroid-treated animals.
Hormonal regulation of albumin gene expression in primary cultures of rat hepatocytes
Authors: Kimball S. R. , Horetsky R. L. , Jefferson L. S.
Published: December 2017

When primary cultures of rat hepatocytes were placed in a chemically defined serum-free medium containing a combination of insulin, glucagon, and dexamethasone, the synthesis of albumin and total protein and the cellular content of RNA and DNA were maintained at constant values for 8 days. Despite the constant rate of albumin synthesis, secretion of the protein increased more than twofold during the initial 4 days in culture and was then maintained at a value similar to that observed in vivo through day 8. This observation suggested an initial defect in albumin secretion that was corrected with time in culture. Deprivation of insulin between days 2 and 5 resulted in a decline in albumin secretion to approximately 40% of the control value. The decline in albumin secretion was accompanied by proportional decreases in albumin synthesis, albumin mRNA, and albumin gene transcription. Return of insulin-deprived cells to complete medium on day 5 restored albumin synthesis and secretion as well as albumin mRNA to control values by day 8. Deprivation of either glucagon or dexamethasone also resulted in reduced albumin synthesis and secretion accompanied by proportional decreases in albumin mRNA and gene transcription. However, the magnitude of the changes in these parameters was less with glucagon or dexamethasone deprivation compared with insulin deprivation. Return of glucagon- or dexamethasone-deprived cells to complete medium on day 5 restored albumin synthesis and secretion as well as albumin mRNA to control values by day 8.(ABSTRACT TRUNCATED AT 250 WORDS)
Tolbutamide inhibits glucagon-induced phosphorylation of 6PF-2-K/Fru-2,6-P2ase in rat hepatocytes
Authors: Ayame H. , Matsutani A. , Inoue H. , Kaneko T. , Kaku K.
Published: December 2017

In previous studies, we demonstrated that tolbutamide inhibits a phosphorylation of hepatic 6-phosphofructo-2-kinase (6PF-2-K)/fructose-2,6-bisphosphatase (Fru-2,6-P2ase) catalyzed by the adenosine 3',5'-cyclic monophosphate-dependent protein kinase in a reconstruction system using the purified enzyme from the rat liver. In the current study, to assess a role of tolbutamide on hepatic 6PF-2-K/Fru-2,6-P2ase physiologically, we used intact rat hepatocytes and examined effects of tolbutamide on a phosphorylation of the bifunctional enzyme in the presence of glucagon. Glucagon induced a rapid phosphorylation of hepatic 6PF-2-K/Fru-2,6-P2ase accompanied by an inhibition of 6PF-2-K activity and a stimulation of Fru-2,6-P2ase activity in a dose-dependent manner. Tolbutamide inhibited glucagon-induced phosphorylation of the bifunctional enzyme protein in a dose-dependent manner. By adding 2 mM tolbutamide, reduced activity of 6PF-2-K and increased activity of Fru-2,6-P2ase in the presence of 10(-9) M glucagon were partially restored. The present results suggest the possibility that tolbutamide modulates the activity of hepatic 6PF-2-K/Fru-2,6-P2ase through inhibiting a phosphorylation of the enzyme protein. The counterregulatory influence of tolbutamide on the effect of glucagon suggests a possible mechanism for the extrapancreatic effect of sulfonylurea drugs.
Metabolism of R-beta-hydroxypentanoate and of beta-ketopentanoate in conscious dogs
Authors: Leclerc J. , Des Rosiers C. , Montgomery J. A. , Brunet J. , Ste-Marie L. , Reider M. W. , Fernandez C. A. , Powers L. , David F. , Brunengraber H.
Published: December 2017

R-beta-Hydroxypentanoate and beta-ketopentanoate are homologues of physiological ketone bodies R-beta-hydroxybutyrate and acetoacetate. They derive from the oxidation in liver of the R-moiety of R,S-1,3-pentanediol, a potential nutrient. This report documents the metabolism of R-beta-hydroxypentanoate and beta-ketopentanoate in conscious dogs. Whether administered by bolus or constant infusion, the two substrates are interconverted and rapidly metabolized. When beta-ketopentanoate was infused at a rate corresponding to 75% of the dog's caloric requirement, the steady-state total plasma concentration of the two substrates was only 1.3 mM. Because the substrates are precursors of propionyl-CoA, we assayed the urinary concentrations of markers of propionic acidemia. Their accumulation was minor compared with what is observed in patients suffering from propionic acidemia. We conclude that, at least during short-term experiments, R-beta-hydroxypentanoate and beta-ketopentanoate are well metabolized in the dog without apparent intolerance to a large supply of propionyl-CoA.
Functional role of intrahypothalamic release of oxytocin and vasopressin: consequences and controversies
Authors: Ludwig M.
Published: December 2017

This brief review of vasopressin (VP) and oxytocin (OT) release into the extracellular space of the supraoptic (SON) and paraventricular (PVN) nuclei focuses on recent data illustrating the significance of their intranuclear release and the potential functional consequences. With the use of in vitro techniques, it has been demonstrated that administration of exogenous OT causes local peptide release and that, in vivo, this facilitates the milk ejection reflex. These findings lead to the idea that endogenous peptides are released into the hypothalamic nuclei. Microperfusion techniques have been used to monitor the dynamics of intranuclear OT and VP release in response to distinct stimuli. It is clear that intranuclear release of OT plays a role during reproductive states (parturition and lactation) and that intranuclear release of VP and OT is involved in osmoregulation. This review discusses 1) the origin of the intranuclearly released peptides, 2) stimuli which cause release into the hypothalamic nuclei, and 3) the function of intranuclear VP and OT, e.g., regulation of local morphology, feedback mechanisms and synchronization, and the possible role in regulating autonomic function and behavior.