PITUITARY GROWTH HORMONE AND THE GLUCOSE UTILIZATION OF RAT DIAPHRAGM

1955 ◽  
Vol 12 (1) ◽  
pp. 50-56 ◽  
Author(s):  
J. H. OTTAWAY ◽  
R. D. BULBROOK
Keyword(s):  
Growth Hormone ◽  
Glucose Uptake ◽  
Glucose Utilization ◽  
Rat Diaphragm ◽  
Pituitary Growth Hormone ◽  
Low Concentrations ◽  
High Concentrations ◽  
The Relationship

SUMMARY Growth hormone has been reported to cause either a depression or a stimulation of the glucose uptake of isolated rat diaphragm. The present paper describes further work on the two effects. 1. Anaerobic conditions during the preparation of the diaphragm for incubation affect the glucose uptake and alter the response of the muscle to growth hormone. By controlling the oxygen tension in the diaphragm immediately after excision, variation of the glucose uptake and the effect of the hormone is reduced. 2. Solutions of growth hormone were found to be extremely labile, but, by rigidly standardizing the method of preparing solutions, consistent results were obtained. 3. The relationship between the concentration of growth hormone and its effect on the glucose uptake of isolated diaphragm was investigated separately for muscle saturated with oxygen and with nitrogen. With oxygenated muscle at high concentrations the hormone stimulates, and at low concentrations depresses, the rate of glucose uptake. 4. The mode of action of growth hormone in vitro and in vivo is discussed.

THE EFFECT OF GROWTH HORMONE AND OF CORTISOL ON THE RESPONSE OF ISOLATED RAT DIAPHRAGM TO THE STIMULATING EFFECT OF INSULIN ON GLUCOSE UPTAKE AND ON INCORPORATION OF AMINO ACIDS INTO PROTEIN

1959 ◽  
Vol 18 (4) ◽  
pp. 395-408 ◽  
Author(s):  
K. L. MANCHESTER ◽  
P. J. RANDLE ◽  
F. G. YOUNG
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Protein Synthesis ◽  
Glucose Uptake ◽  
Carbohydrate Metabolism ◽  
Rat Diaphragm ◽  
Pituitary Growth Hormone ◽  
Isolated Rat ◽  
Stimulation Of

SUMMARY 1. The effect of hypophysectomy, or of adrenalectomy, and injection of pituitary growth hormone (GH) or of cortisol, on the uptake of glucose and the incorporation of glycine into protein by isolated rat diaphragm, and the effect of the addition of insulin in vitro on these processes, has been studied. 2. Both hypophysectomy and adrenalectomy raised the uptake of glucose by isolated diaphragm, while treatment of the intact or of the hypophysectomized rat with GH, or of the intact or of the adrenalectomized rat with cortisol, depressed it. Although hypophysectomy and adrenalectomy did not influence the additional glucose uptake induced by 200 mu./ml. of insulin in vitro, both these operations enhanced the effect of 0·1–1·0 mu./ml. of insulin on glucose uptake by diaphragm in vitro. Treatment of the rat with GH or cortisol diminished the rise in glucose uptake of diaphragm induced by 0·1–1·0 mu./ml. insulin. 3. Hypophysectomy depressed, and administration of GH to the intact or hypophysectomized rat raised, the incorporation of glycine into protein of the isolated diaphragm, but neither of these operations altered the magnitude of the stimulation of incorporation induced by 1·0 mu./ml. insulin. 4. Adrenalectomy raised, and administration of cortisol to the intact or adrenalectomized rat depressed, the incorporation of glycine into protein of the isolated diaphragm; adrenalectomy enhanced, the injection of cortisol diminished, the effect of 1·0 mu./ml. insulin on these processes. 5. The possibility that GH directs insulin towards the stimulation of protein synthesis, in part by restraining the action of insulin on carbohydrate metabolism, is discussed.

Action of epinephrine on muscle glucose uptake depending on Ca++ and phosphate

1965 ◽  
Vol 209 (2) ◽  
pp. 359-364 ◽  
Author(s):  
Michio Ui
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Inorganic Phosphate ◽  
Glucose Utilization ◽  
Rat Diaphragm ◽  
Muscle Tissues ◽  
Ph Level ◽  
Diaphragm In Vitro

Studies have been made of the involvement of inorganic phosphate (Pi) and Ca++ in the mechanism by which epinephrine-induced inhibition of muscle glucose utilization was abolished during either alkalosis in vivo or incubation of the isolated rat diaphragm in vitro at a higher pH level. An increase in the concentration of Pi in muscle tissues was closely associated with prevention of the inhibitory action of epinephrine on glucose uptake. The interrelationship of Ca++ and Pi in aqueous solutions, and the additional observations that glucose uptake by rat diaphragm was accelerated in anaerobiosis only in the absence of Ca++, indicate a significance of Ca++ in muscle glucose metabolism. Assay of hexokinase activity in cell-free muscle preparations revealed that the inhibition of the enzyme activity by glucose 6-phosphate was profoundly influenced by the presence of Ca++ and Pi and was dependent on the concentration of ATP. It is suggested that Ca++ may provide the primary point of influence of epinephrine on glucose metabolism of the muscle.

PURIFICATION AND PROPERTIES OF A HYPOGLYCAEMIC PEPTIDE FROM OX GROWTH HORMONE

1961 ◽  
Vol 23 (2) ◽  
pp. 193-207 ◽  
Author(s):  
A. K. HUGGINS ◽  
J. H. OTTAWAY
Keyword(s):  
Growth Hormone ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Rat Diaphragm ◽  
Low Concentrations ◽  
Purification And Properties ◽  
Lactate Output ◽  
Normal Rat ◽  
High Concentrations ◽  
Very High

SUMMARY A peptide has been isolated from crystalline ox growth hormone (GH) which stimulates glucose uptake by isolated rat diaphragm when incubated with it at low concentrations (0·01 μg./ml. medium). The peptide also causes a slight but persistent hypoglycaemia in fasted mice and rabbits. The increase in glucose uptake by diaphragm is not accompanied by increased glycogen synthesis; in certain circumstances it causes a diminution in lactate output. When incubated with normal rat diaphragm in the absence of acetate, very high concentrations (10 μg./ml.) cause an inhibition of glucose uptake. The peptide appears to have negligible effects on fat metabolism. The peptide has a mol. wt. of 5,000–10,000, an isoelectric point of about pH 6, and an N-terminal methionine. The amino acid composition is noteworthy for the complete absence of basic amino acids. It is concluded that ox GH freed from this peptide will stimulate glycogen synthesis by muscle without increasing the uptake of glucose.

SENSITIVITY OF THE RAT DIAPHRAGM TO GROWTH HORMONE

1968 ◽  
Vol 57 (3_Suppl) ◽  
pp. S1-S17 ◽  
Author(s):  
Å. Hjalmarson
Keyword(s):  
Growth Hormone ◽  
Glucose Utilization ◽  
Inhibitory Effect ◽  
Rat Diaphragm ◽  
Intracellular Accumulation ◽  
Dual Nature ◽  
Hypophysectomized Rats ◽  
Dose Levels

ABSTRACT In vitro administration of bovine growth hormone (GH) to intact hemidiaphragms from hypophysectomized rats was found to produce both an early stimulatory and a late inhibitory effect on the rate of intracellular accumulation of α-aminoisobutyric acid (AIB) and D-xylose. These effects were obtained by using an in vitro system, in which the diaphragms were incubated for periods up to 5 hours, a procedure found suitable for studying early and late effects of GH in vitro. GH (25 μg/ml) was added at the start of incubation and after various lengths of exposure to the hormone the diaphragms were transferred to other flasks and were incubated with AIB-14C (for 60 min) or D-xylose-14C (for 30 min). The stimulatory effect produced by GH on the uptake of the labelled substances in the diaphragm was seen during 2—3 hours after the initial addition of the hormone. The duration of the corresponding stimulatory effect of insulin was at least 4½ hours. Exposure of the diaphragms in vitro to GH in a concentration of 5 μg/ml for 3 hours made the diaphragms almost completely insensitive to further addition of GH (25 μg/ml) later on, when the ability of the muscles to accumulate AIB-14C and D-xylose-14C was studied. Thus, a late inhibitory effect of GH on the membrane transport of AIB and D-xylose in the diaphragm was obtained after in vitro administration of the hormone. The biphasic action of GH in vitro on the accumulation of AIB and D-xylose does not seem to be secondary to GH-produced changes of the glucose utilization in the diaphragm. This phenomenon cannot be explained by different dose levels of GH either, since qualitatively the same effects were obtained by GH at different concentrations from 0.1 to 100 μg/ml medium. The results from the present study are discussed in relation to available observations of the dual nature of GH exerted both in vivo and in vitro.

scholarly journals Hypogonadism associated withCyp19a1 (Aromatase) post-transcriptional upregulation inCelf1-KO mice

2015 ◽  
pp. MCB.00074-15 ◽  
Author(s):  
Gaella Boulanger ◽  
Marie Cibois ◽  
Justine Viet ◽  
Alexis Fostier ◽  
Stéphane Deschamps ◽  
...  
Keyword(s):  
Rna Binding ◽  
Hypogonadotropic Hypogonadism ◽  
Type I ◽  
Male Gametes ◽  
Low Concentrations ◽  
Reporter Assays ◽  
High Concentrations ◽  
In Vitro Interaction

CELF1 is a multifunctional RNA-binding protein that controls several aspects of RNA fate. The targeted disruption of theCelf1gene in mice causes male infertility due to impaired spermiogenesis, the post-meiotic differentiation of male gametes. Here, we investigated the molecular reasons that underlie this testicular phenotype. By measuring sex hormone levels, we detected low concentrations of testosterone inCelf1-null mice. We investigated the effect ofCelf1disruption on the expression levels of steroidogenic enzyme genes, and we observed thatCyp19a1was upregulated.Cyp19a1encodes aromatase, which transforms testosterone into estradiol. Administration of testosterone or the aromatase inhibitor Letrozole partly rescued the spermiogenesis defects, indicating that a lack of testosterone associated with excessive aromatase contributes to the testicular phenotype. In vivo and in vitro interaction assays demonstrated that CELF1 binds toCyp19a1mRNA, and reporter assays supported the conclusion that CELF1 directly repressesCyp19a1translation. We conclude that CELF1 downregulatesCyp19a1/Aromatasepost-transcriptionally to achieve high concentrations of testosterone compatible with spermiogenesis completion. We discuss the implications of these findings with respect to reproductive defects in men, including patients suffering from isolated hypogonadotropic hypogonadism and myotonic dystrophy type I.

Effects of polymethoxylated flavone metabolites on apoB100 secretion and MTP activity in Huh7.5 cells

2021 ◽  
Vol 18 ◽  
Author(s):  
Danielle R. Gonçalves ◽  
Thais B. Cesar ◽  
John A. Manthey ◽  
Paulo I. Costa
Keyword(s):  
Lipid Synthesis ◽  
Dependent Manner ◽  
Transfer Protein ◽  
Low Concentrations ◽  
Wide Range ◽  
Cell Assays ◽  
Polymethoxylated Flavones ◽  
High Concentrations

Background: Citrus polymethoxylated flavones (PMFs) reduce the synthesis of liver lipoproteins in animal and in vitro cell assays, but few studies have evaluated the direct effects of their metabolites on this highly regulated process. Objective: To investigate the effects of representative metabolites of PMF on the secretion of liver lipoproteins using the mammalian cell Huh7.5. Method: In this study, the influences of three PMFs and five previously isolated PMF metabolites on hepatic apoB-100 secretion and microsomal transfer protein (MTP) activity were evaluated. Tangeretin (TAN), nobiletin (NOB) and 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), and their glucuronides (TAN-Gluc, NOB-Gluc and HMF-Gluc) and oxidatively demethylated metabolites (TAN-OH, NOB-OH, HMF-OH) were incubated with Huh7.5 cells to measure their inhibitory effects on lipid synthesis. Results: The results showed that TAN, HMF and TAN-OH reduced the secretion of apoB-100 in a dose-dependent manner, while NOB and the other tested metabolites showed no inhibition. MTP activity in the Huh7.5 cells was significantly reduced in the presence of low concentrations of TAN, and in high concentrations of NOB-OH. This study also showed that PMFs and PMF metabolites produced a wide range of effects on apoB-100 secretion and MTP activity. Conclusion: The results suggest that while PMFs and their metabolites control dyslipidemia in vivo, the inhibition of MTP activity cannot be the only pathway influenced by these compounds.

Abstract 344: FNDC5, a PGC1-a-Dependent Myokine, Increases Glucose Utilization and Fatty-Acid Oxidation by AMPK Signaling Pathway

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Ling Tao ◽  
Yi Liu ◽  
Chao Xin ◽  
Weidong Huang ◽  
Lijian Zhang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Glucose Uptake ◽  
Fatty Acid Oxidation ◽  
Glucose Utilization ◽  
C2c12 Cells ◽  
Time Dependent ◽  
Acid Oxidation ◽  
Ampk Signaling

FNDC5 is a hormone secreted by myocytes that could reduce obesity and insulin resistance, However, the exact effect of FNDC5 on glucose and lipid metabolism remain poorly identified; More importantly, the signaling pathways that mediate the metabolic effects of FNDC5 is completely unknown. Here we showed that FNDC5 stimulates β-oxidation and glucose uptake in C2C12 cells in a dose- and time-dependent fashion in vitro (n=8, all P<0.01). In vivo study revealed that FNDC5 also enhanced glucose tolerance in diabetic mice and increased the glucose uptake evidenced by increased [18F] FDG accumulation in hearts by PET scan (n=6, all P<0.05). FNDC5 decreased the expression of gluconeogenesis related molecules (PEPCK and G6Pase) and increased the phosphorylation of ACC, a key modulator of fatty-acid oxidation, both in hepatocytes and C2C12 cells (n=3, all P<0.05). In parallel with its stimulation of β-oxidation and glucose uptake, FNDC5 increased the phosphorylation of AMPK both in hepatocytes and C2C12 cells in a dose- and time-dependent fashion in vitro and in vivo. More importantly, the β-oxidation and glucose uptake, the expression of PEPCK and G6Pase and the phosphorylation of ACC induced by FNDC5 were attenuated by AMPK inhibitor in hepatocytes and C2C12 cells (P<0.05). Most importantly, the FNDC5 induced glucose uptake and phosphorylation of ACC were attenuated in AMPK-DN mice (n=6, all P<0.05). The glucose-lowering effect of FNDC5 in diabetic mice was also attenuated by AMPK inhibitor. Our data presents the direct evidence that FNDC5 stimulates glucose utilization and fatty-acid oxidation by AMPK signaling pathway, suggesting that FNDC5 be a novel pharmacological approach for type 2 diabetes.

Stimulation and inhibition of FVIII-specific memory B-cell responses by CpG-B (ODN 1826), a ligand for Toll-like receptor 9

Blood ◽  
2011 ◽  
Vol 117 (1) ◽  
pp. 259-267 ◽  
Author(s):  
Peter Allacher ◽  
Christina K. Baumgartner ◽  
Aniko G. Pordes ◽  
Rafi U. Ahmad ◽  
Hans Peter Schwarz ◽  
...  
Keyword(s):  
B Cells ◽  
Memory B Cells ◽  
Cpg Odn ◽  
Specific Memory ◽  
Cpg Oligodeoxynucleotide ◽  
Low Concentrations ◽  
Essential Components ◽  
High Concentrations

Abstract Factor VIII (FVIII)–specific memory B cells are essential components for regulating anamnestic antibody responses against FVIII in hemophilia A with FVIII inhibitors. We asked how stimulation and inhibition of FVIII-specific memory B cells by low and high concentrations of FVIII, respectively, are affected by concurrent activation of the innate immune system. Using CD138− spleen cells from hemophilic mice treated with FVIII to study restimulation and differentiation of memory B cells in vitro, we tested modulating activities of agonists for Toll-like receptors (TLRs) 2, 3, 4, 5, 7, and 9. Ligands for TLR7 and 9 were most effective. They not only amplified FVIII-specific memory responses in the presence of stimulating concentrations of FVIII, but also countered inhibition in the presence of inhibitory concentrations of FVIII. Notably, CpG oligodeoxynucleotide (CpG-ODN), a ligand for TLR9, expressed biphasic effects. It amplified memory responses at low concentrations and inhibited memory responses at high concentrations, both in vitro and in vivo. Both stimulatory and inhibitory activities of CpG-ODN resulted from specific interactions with TLR9. Despite their strong immunomodulatory effects in the presence of FVIII, ligands for TLR induced negligible restimulation in the absence of FVIII in vitro and no restimulation in the absence of FVIII in vivo.

In vitro Effect of Growth Hormone on the Glucose Uptake of Isolated Rat Diaphragm

Nature ◽  
1957 ◽  
Vol 179 (4557) ◽  
pp. 472-473 ◽  
Author(s):  
P. J. RANDLE ◽  
J. E. WHITNEY
Keyword(s):  
Growth Hormone ◽  
Glucose Uptake ◽  
Rat Diaphragm ◽  
Vitro Effect ◽  
Isolated Rat

Comparison of in vivo and in vitro Actions of Various Ox Pituitary Growth Hormone Fractions

Nature ◽  
1963 ◽  
Vol 200 (4909) ◽  
pp. 888-889 ◽  
Author(s):  
K. L. MANCHESTER ◽  
M. WALLIS
Keyword(s):  
Growth Hormone ◽  
Pituitary Growth Hormone
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