scholarly journals Histone H4 stimulates glucose transport activity in rat skeletal muscle

1993 ◽  
Vol 295 (2) ◽  
pp. 549-553 ◽  
Author(s):  
L L Louters ◽  
E J Henriksen ◽  
C M Tipton
Keyword(s):  
Glucose Transport ◽  
Specific Binding ◽  
Insulin Receptors ◽  
Complex Signal ◽  
Scatchard Analysis ◽  
Maximal Effect ◽  
Histone H4 ◽  
Transport Activity ◽  
Igf I ◽  
Flexor Digitorum Brevis

We investigated the effects of purified histone H4 on glucose transport activity in rat soleus and flexor digitorum brevis muscles. Histone H4, at concentrations up to 11.8 microM, increased 2-deoxyglucose (2-DG) uptake in a dose-dependent fashion. However, at concentrations higher than 11.8 microM, H4 caused a decrease in 2-DG uptake from the maximum, suggesting a secondary inhibitory action of this compound. The maximal effect of H4 on 2-DG uptake was not additive to the maximal effect of insulin. Moreover, 2-DG uptake in the presence of both H4 and insulin was significantly lower than the 2-DG uptake in the presence of insulin alone. The maximal effect of H4 on stimulation of 2-DG uptake was neither additive nor inhibitory to the maximal effects of the intracellularly acting insulin mimetics sodium vanadate or H2O2. It was, on the other hand, additive to the maximal effects of muscle contractions. Also, in contrast with the effects of H4 on insulin-stimulated 2-DG uptake, H4 did not inhibit insulin-like growth factor-I (IGF-I)-stimulated 2-DG uptake, as the maximal effects of H4 and IGF-I were additive. Scatchard analysis of the binding of 125I-insulin in the absence or presence of histone H4 revealed that H4 increased the specific binding of insulin without affecting receptor affinity. These data suggest that H4 interacts with the insulin, rather than the hypoxia/contraction, pathway for activation of glucose transport in muscle tissue, and that H4 acts either directly or indirectly to increase the number of insulin receptors at the surface of the muscle cell. This interaction does not appear to occur with the similar, although distinct, IGF-I receptor. These studies may provide additional insight into the complex signal-transduction systems of insulin action.

Glucose transporters and glucose transport in skeletal muscles of 1- to 25-mo-old rats

1993 ◽  
Vol 264 (3) ◽  
pp. E319-E327 ◽  
Author(s):  
E. A. Gulve ◽  
E. J. Henriksen ◽  
K. J. Rodnick ◽  
J. H. Youn ◽  
J. O. Holloszy
Keyword(s):  
Glucose Transport ◽  
Skeletal Muscles ◽  
Glucose Transporter ◽  
Contractile Activity ◽  
Transport Activity ◽  
Glut 4 ◽  
Flexor Digitorum Brevis ◽  
Old Rats ◽  
Growth And Aging ◽  
Flexor Digitorum

It is widely thought that aging results in development of insulin resistance in skeletal muscle. In this study, we examined the effects of growth and aging on the concentration of the GLUT-4 glucose transporter and on glucose transport activity in skeletal muscles of female Long-Evans rats. Relative amounts of immunoreactive GLUT-4 protein were measured in muscle homogenates of 1-, 10-, and 25-mo-old rats by immunoblotting with a polyclonal antibody directed against GLUT-4. In the epitrochlearis, plantaris, and the red and white regions of the quadriceps muscles, GLUT-4 immunoreactivity decreased by 14-33% between 1 and 10 mo of age and thereafter remained constant. In flexor digitorum brevis (FDB) and soleus muscles, GLUT-4 concentration was similar at all three ages studied. Glucose transport activity was assessed in epitrochlearis and FDB muscles by incubation with 2-deoxyglucose under the following conditions: basal, submaximal insulin, and either maximal insulin or maximal insulin combined with contractile activity. Glucose transport in the epitrochlearis muscle decreased by approximately 60% between 1 and 4 mo of age and then did not decline further between 4 and 25 mo of age. Transport activity in the FDB assessed with a maximally effective insulin concentration decreased only slightly (< 20%) between 1 and 7 mo of age. Aging, i.e., the transition from young adulthood to old age, was not associated with a decrease in glucose transport activity in either the epitrochlearis or the FDB.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of insulin-like growth factor receptors in primary human thyroid neoplasms

1989 ◽  
Vol 121 (1) ◽  
pp. 112-120 ◽  
Author(s):  
Tohru Yashiro ◽  
Yoshito Ohba ◽  
Hitomi Murakami ◽  
Takao Obara ◽  
Toshio Tsushima ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Binding Capacity ◽  
Specific Binding ◽  
Human Thyroid ◽  
Scatchard Analysis ◽  
Type I ◽  
Single Class ◽  
Normal Tissues ◽  
Igf I ◽  
Cancer Tissues

Abstract. The presence of IGF-I receptors was demonstrated in normal and neoplastic tissues of human thyroid. Binding of [125I]IGF-I to thyroid membranes was dependent on time and temperature of incubation, and maximal binding was achieved at 4°C and 18 h of incubation. [125I] IGF-I binding was dose-dependently displaced by unlabelled IGF-I; half-maximal inhibition occurred at concentrations of 10–20 μg/l. IGF-II and insulin had relative potencies of 5 and 1% compared with IGF-I. Scatchard analysis of binding data revealed a single class of IGF-I receptors with high affinity (Ka: 1.2–8.6 × 109 1/mol) in normal thyroid tissues. Affinity cross-linking and autoradiography demonstrated the type I IGF receptors. Specific binding of [125I] IGF-I in thyroid cancer tissues (9.69 ± 2.07% per 200 μg protein; mean ± sem, N = 8) was significantly (p <0.05) higher than that in the surrounding normal tissues (3.03 ± 0.35%, N = 8). In contrast, there was no difference in the binding between adenoma tissues (4.19 ± 0.53%, N = 5) and the adjacent normal tissues (2.94 ± 0.24%, N = 5). The higher IGF-I binding in cancer tissues was due to an increase in the binding capacity without any change in the affinity. The presence of IGF-I receptors suggests a possible role of IGF-I and its receptors in the growth of thyroid cancer cells.

Glucose transport with brief dietary restriction: heterogenous responses in muscles

1994 ◽  
Vol 266 (6) ◽  
pp. E946-E952 ◽  
Author(s):  
G. D. Cartee ◽  
D. J. Dean
Keyword(s):  
Glucose Transport ◽  
Dietary Restriction ◽  
Time Course ◽  
Abdominal Fat ◽  
Transport Activity ◽  
Fischer 344 ◽  
Flexor Digitorum Brevis ◽  
Ad Libitum ◽  
Ad Libitum Intake ◽  
Flexor Digitorum

The time course (1, 5, or 20 days) for the effect of dietary restriction (DR; approximately 25% reduction below ad libitum intake) on epitrochlearis and flexor digitorum brevis (FDB) muscle glucose transport activity was studied in female Fischer 344 rats (8 mo old). Epitrochlearis glucose transport activity with 100 microU/ml insulin was increased by 38% after 5 days of DR (P < 0.05) despite no change in glucose transport activity with 0 or 20,000 microU/ml insulin. The increase with 100 microU/ml insulin was not further enhanced by 20 days of DR. DR did not result in a significant increase in the glucose transport activity of the FDB with 0, 100, or 20,000 microU/ml insulin. Abdominal fat content was significantly (P < 0.01) reduced below ad libitum levels only after 20 days of DR. These results demonstrate that DR-induced improvement in epitrochlearis glucose transport activity with a physiological insulin concentration can occur very rapidly, preceding detectable changes in basal or maximal insulin-stimulated glucose transport activity or abdominal fat pad mass, and the enhancement of insulin action does not occur simultaneously in all muscles.

Erythrocytes from patients with low serum concentrations of IGF-I have an increase in receptor sites for IGF-I

1991 ◽  
Vol 125 (4) ◽  
pp. 354-358 ◽  
Author(s):  
R. Eshet ◽  
Z. Dux ◽  
A. Silbergeld ◽  
R. Koren ◽  
B. Klinger ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Specific Binding ◽  
Hormone Deficiency ◽  
Scatchard Analysis ◽  
Isolated Growth Hormone Deficiency ◽  
Receptor Sites ◽  
Igf I ◽  
The Mean ◽  
Low Serum

Abstract. The binding characteristics of insulin-like growth factor I on erythrocytes were studied in 11 patients with long-term IGF-I deprivation and low serum IGF-I levels. Six patients had Laron type dwarfism and 5 idiopathic isolated growth hormone deficiency, with a mean (± sem) serum IGF-I level of 6.01±1.01 nmol/l as compared with that in 25 normal controls of 26.35±2.73 nmol/l (p=0.00001). The mean (± sem) [125I]IGF-I specific binding at a concentration of 4×1012 cell/l was 12.11±1.29% for the patient group compared with 8.75±0.62% for the controls (p=0.005). Scatchard analysis showed a curvilinear plot. Using a non-linear curve fit, the mean (± sem) number of high-affinity receptor sites per cell was found to be 7.34±1.80 in the IGF-I-deprived patients and 2.84±0.29 in the controls (p=0.0005). The mean ± sem dissociation constant was found to be 0.33±0.10 nmol/l for the patients and 0.26±0.08 nmol/l for the controls (NS). This study has demonstrated that the low serum concentration of IGF-I in Laron type dwarfism and isolated growth hormone deficiency is associated with an increase in receptor sites for IGF-I on the erythrocytes. The application of this property as a diagnostic aid remains to be established.

scholarly journals Development of the hormone-sensitive glucose transport activity in differentiating 3T3-L1 murine fibroblasts. Role of the two transporter species and their subcellular localization

1990 ◽  
Vol 270 (2) ◽  
pp. 331-336 ◽  
Author(s):  
M Weiland ◽  
A Schürmann ◽  
W E Schmidt ◽  
H G Joost
Keyword(s):  
Glucose Transport ◽  
Plasma Membranes ◽  
Glucose Transporter ◽  
Transport Activity ◽  
Intracellular Compartment ◽  
Differentiated Cells ◽  
Murine Fibroblasts ◽  
Igf I ◽  
Undifferentiated Cells ◽  
Hormone Sensitive

The development of a hormone-responsive glucose transport activity during differentiation of 3T3-L1 murine fibroblasts to an insulin-sensitive adipocyte-like phenotype was studied. Glucose transport activity was insensitive to insulin or insulin-like growth factor I (IGF-I) before differentiation, and was increased by 8-10-fold after differentiation by both insulin and IGF-I via their own respective receptors. In contrast, in undifferentiated cells insulin and IGF-I stimulated a large increase of [3H]thymidine incorporation into DNA via IGF-I receptors, indicating that undifferentiated 3T3-L1 cells are equipped with fully functioning hormone (IGF-I) receptors. Thus the previously described increase in expression of insulin receptors during differentiation cannot solely account for the development of hormone-sensitive glucose transport in the 3T3-L1 cell. The total glucose transport activity reconstituted from membrane fractions was increased by about 3-fold during differentiation. In differentiated cells, more than 80% of the total reconstitutable glucose transport activity was detected in an intracellular compartment (200,000 g microsomes) as compared with about 20% in undifferentiated cells. Immunoblots with specific antiserum confirmed previous reports indicating that the adipose tissue/muscle glucose transporter (GT3) was exclusively present in the differentiated cells, whereas the erythrocyte/brain glucose transporter (GT1) was detected in both differentiated and undifferentiated cells. Upon differentiation, GT1 was redistributed from plasma membranes to the intracellular compartment. In addition, the newly formed GT3 was predominantly found (greater than 80% of total) in the microsomal fraction of differentiated cells. Both GT1 and GT3 appeared to be hormone-sensitive, since in differentiated cells insulin as well as IGF-I gave rise to their translocation from the intracellular compartment to the plasma membrane. These data suggest that, in addition to the specific expression of the GT3 transporter, the formation of a large pool of intracellular glucose transporters comprising both GT1 and GT3 contributes to the development of insulin sensitivity in the 3T3-L1 cell.

The binding of insulin-like growth factor II to the erythroleukemia cell line K562

1984 ◽  
Vol 4 (12) ◽  
pp. 1071-1077 ◽  
Author(s):  
Michael Tally ◽  
Tang Xin-Zhi ◽  
Gösta Enberg ◽  
Kerstin Hall
Keyword(s):  
Growth Factor ◽  
Cell Line ◽  
Specific Binding ◽  
Affinity Constant ◽  
Scatchard Analysis ◽  
Insulin Like Growth Factor ◽  
Factor Ii ◽  
Igf I ◽  
Erythroleukemia Cell ◽  
High Concentrations

The erythroleukemia cell line K562 was previously shown to have specific binding sites for insulin but not for insulin-like growth factor I (IGF-I). In this study the presence of specific receptors for insulin-like growth factor II (IGFqI) is established. Scatchard analysis of the competition curve for IGF-II disclosed a non-cooperative binding kinetic with a calculated affinity constant of 2.4 × 108 M−1 and a receptor number of 4.8 × 104 sites/cell. IGF-I displayed 10% crossreactivity over the IGF-II receptor but insulin did not crossreact at all. Instead insulin, present in high concentrations, enhanced the binding of IGF-II. The presence of IGF II but not IGF-I receptors makes the K562 cell line suitable for studying properties of the type-2 receptor.

Characterization of human glucose transporter (GLUT) 11 (encoded by SLC2A11), a novel sugar-transport facilitator specifically expressed in heart and skeletal muscle

2001 ◽  
Vol 359 (2) ◽  
pp. 443-449 ◽  
Author(s):  
Holger DOEGE ◽  
Andreas BOCIANSKI ◽  
Andrea SCHEEPERS ◽  
Hubertus AXER ◽  
Jürgen ECKEL ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Specific Binding ◽  
Sequence Similarity ◽  
Sugar Transport ◽  
Amino Acid Identity ◽  
Sugar Transporter ◽  
Transport Activity

Human GLUT11 (encoded by the solute carrier 2A11 gene, SLC2A11) is a novel sugar transporter which exhibits significant sequence similarity with the members of the GLUT family. The amino acid sequence deduced from its cDNAs predicts 12 putative membrane-spanning helices and all the motifs (sugar-transporter signatures) that have previously been shown to be essential for sugar-transport activity. The closest relative of GLUT11 is the fructose transporter GLUT5 (sharing 41.7% amino acid identity with GLUT11). The human GLUT11 gene (SLC2A11) consists of 12 exons and is located on chromosome 22q11.2. In human tissues, a 7.2kb transcript of GLUT11 was detected exclusively in heart and skeletal muscle. Transfection of COS-7 cells with GLUT11 cDNA significantly increased the glucose-transport activity reconstituted from membrane extracts as well as the specific binding of the sugar-transporter ligand cytochalasin B. In contrast to that of GLUT4, the glucose-transport activity of GLUT11 was markedly inhibited by fructose. It is concluded that GLUT11 is a novel, muscle-specific transport facilitator that is a member of the extended GLUT family of sugar/polyol-transport facilitators.

scholarly journals Presence of insulin receptors in cultured glial C6 cells. Regulation by butyrate

1989 ◽  
Vol 258 (1) ◽  
pp. 147-155 ◽  
Author(s):  
F Montiel ◽  
J Ortiz-Caro ◽  
A Villa ◽  
A Pascual ◽  
A Aranda
Keyword(s):  
Fatty Acids ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Scatchard Analysis ◽  
Maximal Effect ◽  
C6 Cells ◽  
Receptor Affinity ◽  
Chain Fatty Acids

The presence of insulin receptor and its regulation by butyrate and other short-chain fatty acids was studied in C6 cells, a rat glioma cell line. Intact C6 cells bind 125I-insulin in a rapid, reversible and specific manner. Scatchard analysis of the binding data gives typical curvilinear plots with apparent affinities of approx. 6 nM and 70 nM for the low-affinity (approx. 90% of total) and high-affinity (approx. 10% of total) sites respectively. Incubation with butyrate results in a time- and dose-dependent decrease of insulin binding to C6 cells. A maximal effect was found with 2 mM-butyrate that decreased the receptor by 40-70% after 48 h. Butyrate decreased numbers of receptors of both classes, but did not significantly alter receptor affinity. Other short-chain fatty acids, as well as keto acids, had a similar effect, but with a lower potency. Cycloheximide caused an accumulation of insulin receptors at the cell surface, since insulin binding increased and receptor affinity did not change after incubation with the inhibitor. Simultaneous addition of butyrate and cycloheximide abolished the loss of receptors produced by the fatty acid. In cells preincubated with butyrate, cycloheximide also produced a large increase in receptor numbers, showing that in the absence of new receptor synthesis a large pool of receptors re-appears at the surface of butyrate-treated cells.

Insulin-like growth factor I receptors are more abundant than insulin receptors in human micro- and macrovascular endothelial cells

2004 ◽  
Vol 286 (6) ◽  
pp. E896-E901 ◽  
Author(s):  
Simona I. Chisalita ◽  
Hans J. Arnqvist
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Dna Synthesis ◽  
Specific Binding ◽  
Insulin Receptors ◽  
Receptor Protein ◽  
Β Subunit ◽  
Igf I ◽  
Long Acting

Micro- and macroangiopathy are major causes of morbidity and mortality in patients with diabetes. Our aim was to characterize IGF-I receptor (IGF-IR) and insulin receptor (IR) in human micro- and macrovascular endothelial cells. Cultured human dermal microvascular endothelial cells (HMVEC) and human aortic endothelial cells (HAEC) were used. Gene expression was measured by quantitative real-time RT-PCR and receptor protein by ligand-binding assay. Phosphorylation of IGF-IR β-subunit was analyzed by immunoprecipitation and Western blot. Glucose metabolism and DNA synthesis was assessed using [3H]glucose and [3H]thymidine incorporation, respectively. We detected gene expression of IGF-IR and IR in HAEC and HMVEC. IGF-IR gene expression was severalfold higher than that of IR. The specific binding of 125I-IGF-I was higher than that of 125I-insulin in HAEC and HMVEC. Insulin and the new, long-acting insulin analog glargine interacted with the IGF-IR with thousand- and hundred-fold less potency than IGF-I itself. Phosphorylation of the IGF-IR β-subunit was shown in HAEC for IGF-I (10−8 M) and insulin (10−6 M) and in HMVEC for IGF-I and glargine (10−8 M, 10−6 M). IGF-I 10−7 M stimulated incorporation of [3H]thymidine into DNA, and 10−9–10−7 M also the incorporation of [3H]glucose in HMVEC, whereas glargine and insulin had no significant effects at 10−9–10−7 M. Human micro- and macrovascular endothelial cells express more IGF-IR than IR. IGF-I and high concentrations of glargine and insulin activates the IGF-IR. Glargine has a higher affinity than insulin for the IGF-IR but probably has no effect on DNA synthesis at concentrations reached in vivo.

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