scholarly journals INSULIN GROWTH FACTOR I AND ITS RECEPTOR ARE ANTAGONISTIC MODULATORS OF GLUCOSE HANDLING BY ASTROCYTES

2015 ◽  
Author(s):  
Edwin Hernandez ◽  
Ana M Fernandez ◽  
Alberto Perez Alvarez ◽  
Sara Mederos ◽  
Paloma Perez Domper ◽  
...  
Keyword(s):  
Growth Factor ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Brain Slices ◽  
Glucose Transporter 1 ◽  
Factor I ◽  
Igf I ◽  
Pharmacological Blockade ◽  
Growth Factor I

Reducing insulin-like growth factor I receptor (IGF-IR) levels or administration of IGF-I show beneficial effects in the brain. We now provide evidence to help resolve this paradox. The unliganded IGF-IR inhibits glucose uptake by astrocytes while its stimulation with IGF-I, in concert with insulin activation of the insulin receptor, produces the opposite effect. In vivo imaging showed that shRNA interference of brain IGF-IR increased glucose uptake by astrocytes while pharmacological blockade of IGF-IR reduced it. Brain 18FGlucose-PET of IGF-IR shRNA injected mice confirmed an inhibitory role of unliganded IGF-IR on glucose uptake, whereas glucose-dependent recovery of neuronal activity in brain slices was blunted by pharmacological blockade of IGF-IR. Mechanistically, we found that the unliganded IGF-IR retains glucose transporter 1 (GLUT1), the main glucose transporter in astrocytes, inside the cell while IGF-I, in cooperation with insulin, synergistically stimulates MAPK/PKD to promote association of IGF-IR with GLUT 1 via Rac1/GIPC1 and increases GLUT1 availability at the cell membrane. These findings identify IGF-I and its receptor as antagonistic modulators of brain glucose uptake.

scholarly journals Regulation of Human Trophoblast GLUT1 Glucose Transporter by Insulin-Like Growth Factor I (IGF-I)

PLoS ONE ◽  
2014 ◽  
Vol 9 (8) ◽  
pp. e106037 ◽  
Author(s):  
Marc U. Baumann ◽  
Henning Schneider ◽  
Antoine Malek ◽  
Vidya Palta ◽  
Daniel V. Surbek ◽  
...  
Keyword(s):  
Growth Factor ◽  
Glucose Transporter ◽  
Insulin Like Growth Factor ◽  
Human Trophoblast ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Glut1 Glucose Transporter

Recombinant growth hormone and insulin-like growth factor I do not alter gonadotrophin stimulation of the baboon testis in vivo

1994 ◽  
Vol 131 (4) ◽  
pp. 405-412 ◽  
Author(s):  
Bronwyn A Crawford ◽  
David J Handelsman
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Recombinant Growth Hormone ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Human Primate ◽  
Stimulation Of

Crawford BA, Handelsman DJ. Recombinant growth hormone and insulin-like growth factor I do not alter gonadotrophin stimulation of the baboon testis in vivo. Eur J Endocrinol 1994;131:405–12. ISSN 0804–4643 In vitro studies indicate a physiological role for insulin-like growth factor I (IGF-I) in paracrine regulation of testicular function and recent clinical studies suggest a potential role for growth hormone (GH) and/or IGF-I in the treatment of hypogonadotrophic states in males. This study aimed to examine the effects of pretreatment with recombinant human GH (rhGH) or rhIGF-I on the response to gonadotrophins of the non-human primate testis in vivo. Using a balanced Latin square design with repeated measures, six prepubertal male hamadryas baboons (Papio hamadryas hamadryas) were treated in a cross-over sequence for periods of 18 days with daily im injections of rhGH (0.4 IU·kg−1 · day−1), rhIGF-I (0.1 mg·kg−1 · day−1) or saline with a 2-week washout period between each treatment. A single im injection of hCG (1500 IU) increased serum testosterone (p = 0.0002) but neither rhGH nor rhIGF-I influenced the timing or magnitude of this response (p > 0.5). A single im dose of FSH (75 IU) stimulated immunoreactive inhibin (p = 0.01) but also was unaffected in magnitude or timing by pretreatment with rhGH or rhIGF-I (p> 0.2). Circulating IGF-I levels were increased independently by hCG (p = 0.01) and FSH (p < 0.0001) administration. These findings indicate that neither GH nor IGF-I pre-treatment enhance acute gonadal responses to gonadotrophin stimulation of the prepubertal non-human primate testis in vivo. These findings suggest that GH or IGF-I treatment of hypogonadotrophic men without somatotrophin deficiency is unlikely to be beneficial. David J Handelsman, Andrology Unit, Royal Prince Alfred Hospital, Departments of Medicine and Obstetrics and Gynaecology, University of Sydney, Sydney 2006, Australia

Insulin-like growth factor I is a dual effector of multiple myeloma cell growth

Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2856-2861 ◽  
Author(s):  
Nie-Lin Ge ◽  
Stuart Rudikoff
Keyword(s):  
Multiple Myeloma ◽  
Growth Factor ◽  
Cell Growth ◽  
Myeloma Cell ◽  
Mitogen Activated Protein Kinase ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Abstract Multiple myeloma (MM) is an invariably fatal disease that accounts for approximately 1% to 2% of all human cancers. Surprisingly little is known about the cellular pathways contributing to growth of these tumors. Although the cytokine interleukin-6 has been suggested to be the major stimulus for myeloma cell growth, the role of a second potential growth factor, insulin-like growth factor I (IGF-I), has been less clearly defined. The IGF-I signaling cascade in 8 MM cell lines was examined. In 7 of these, the IGF-I receptor (IGF-IR) was expressed and autophosphorylated in response to ligand. Downstream of IGF-IR, insulin receptor substrate 1 was phosphorylated, leading to the activation of phosphatidylinositol-3′-kinase (PI-3K). PI-3K, in turn, regulated 2 distinct pathways. The first included Akt and Bad, leading to an inhibition of apoptosis; the second included the mitogen-activated protein kinase (MAPK), resulting in proliferation. Biologic relevance of this pathway was demonstrated because in vitro IGF-I induced both an antiapoptotic and a proliferative effect. Importantly, in vivo administration of IGF-I in SCID mice inoculated with the OPM-2 line led to approximately twice the growth rate of tumor cells as in controls. These results suggest that IGF-I activates at least 2 pathways effecting myeloma cell growth and contributes significantly to expansion of these cells in vivo.

Increase in tendon protein synthesis in response to insulin-like growth factor-I is preserved in elderly men

2014 ◽  
Vol 116 (1) ◽  
pp. 42-46 ◽  
Author(s):  
Rie Harboe Nielsen ◽  
Lars Holm ◽  
Nikolaj Mølkjær Malmgaard-Clausen ◽  
Søren Reitelseder ◽  
Katja Maria Heinemeier ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Growth Factor ◽  
Age Groups ◽  
Synthesis Rate ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Old Men

Insulin-like growth factor-I (IGF-I) is known to be an anabolic factor in tendon, and the systemic levels are reduced with aging. However, it is uncertain how tendon fibroblasts are involved in tendon aging and how aging cells respond to IGF-I. The purpose of this study was to investigate the in vivo IGF-I stimulation of tendon protein synthesis in elderly compared with young men. We injected IGF-I in the patellar tendons of young ( n = 11, 20–30 yr of age) and old ( n = 11, 66–75 yr of age) men, and the acute fractional synthesis rate (FSR) of tendon protein was measured with the stable isotope technique and compared with the contralateral side (injected with saline as control). We found that tendons injected with IGF-I had significantly higher protein FSR compared with controls (old group: 0.018 ± 0.015 vs. 0.008 ± 0.008, young group: 0.016 ± 0.009 vs. 0.009 ± 0.006%/h, mean ± SE, P < 0.01). This increase in protein synthesis was seen in both young and old men, with no differences between age groups. The old group had markedly lower serum IGF-I levels compared with young (165 ± 17 vs. 281 ± 27 ng/ml, P < 0.01). In conclusion, local IGF-I stimulated tendon protein synthesis in both young and old men, despite lower systemic IGF-I levels in the old group. This could indicate that the changed phenotype in aging tendon is not caused by decreased fibroblast function.

Post-thaw culture in presence of insulin-like growth factor I improves the quality of cattle cryopreserved embryos

Zygote ◽  
2011 ◽  
Vol 20 (2) ◽  
pp. 97-102 ◽  
Author(s):  
Alexander V. Makarevich ◽  
Elena Kubovičová ◽  
Zdena Hegedušová ◽  
Juraj Pivko ◽  
František Louda
Keyword(s):  
Growth Factor ◽  
Cell Number ◽  
Embryo Cell ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
Cryopreserved Embryos

SummaryThe goal of this study was to examine the effect of insulin-like growth factor I (IGF-I; added during post-thaw culture (48 h)) on the preimplantation viability and quality of cryopreserved bovine in vivo recovered embryos. The morula stage embryos, non-surgically recovered from superovulated dairy cows of Czech Fleckvieh cattle breed, had previously been cryopreserved by a slow freezing technique and stored in liquid nitrogen since 1989–1990. Following thawing, the embryos were cultured for 48 h either alone (no IGF-I) or in the presence of IGF-I (10 or 100 ng/ml); non-cultured embryos served as a control. Thereafter, the embryos were analyzed for cleavage to the blastocyst stage, apoptosis (TUNEL), embryo cell number and quality of actin cytoskeleton. Following post-thaw culture 41% of embryos developed to advanced blastocysts. IGF-I increased this per cent and, at a higher dose, essentially reduced the per cent of degenerated embryos. In cultured embryos, IGF-I at both doses elevated the cell number compared with non-cultured embryos. However, in comparison with embryos cultured without IGF-I, only the higher IGF-I dose resulted in elevating the embryo cell number. The TUNEL index was significantly lowered by IGF-I treatment. Thawed embryos were mostly of the grade III actin type and fewer (12%) had grade II actin, whilst no grade I actin embryos were noted. The addition of IGF-I resulted in the appearance of grade I actin embryos (8.33 and 6.9% for 10 and 100 ng/ml, respectively). These observations indicate that the addition of IGF-I during post-thaw culture can improve the quality of bovine cryopreserved embryos.

In vivo expression of the insulin-like growth factor-I (IGF-I) receptor in congenital pigmented nevi

1996 ◽  
Vol 23 (1) ◽  
pp. 19-24 ◽  
Author(s):  
E. Hodak ◽  
A.B. Gottlieb ◽  
S. Colen ◽  
M. Anzilotti ◽  
J.G. Krueger
Keyword(s):  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
In Vivo Expression ◽  
Growth Factor I ◽  
Pigmented Nevi

Insulin-like growth factor-I-stimulated glucose transport in myotubes derived from chicken muscle satellite cells

1993 ◽  
Vol 137 (3) ◽  
pp. 465-472 ◽  
Author(s):  
M. J. Duclos ◽  
B. Chevalier ◽  
Y. Le Marchand-Brustel ◽  
J. F. Tanti ◽  
C. Goddard ◽  
...  
Keyword(s):  
Growth Factor ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Satellite Cells ◽  
Glucose Concentration ◽  
Insulin Like Growth Factor ◽  
Muscle Satellite Cells ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

ABSTRACT The effects of insulin and insulin-like growth factor-I (IGF-I) on glucose transport were compared in myotubes derived from chicken breast muscle satellite cells in vitro. Myotubes were incubated (for 0·5 or 4 h) with or without glucose in the presence or absence of insulin or IGF-I. Glucose uptake was subsequently measured by the incorporation of 2-[1,2-3H(N)] deoxy-d-glucose ([3H]2DG) in glucose-free medium (10 min at 20 °C). Glucose uptake was almost completely abolished by the addition of cytochalasin B or phloretin. It was increased by a decrease in glucose concentration in the incubation medium. Insulin (5 mg/l) stimulated [3H]2DG uptake to a maximum of 43 ± 10% above basal after 30-min incubation and 101 ± 15% after 4-h incubation. IGF-I and insulin at equimolar concentrations (25 μg/l and 20 μg/l respectively) were almost equipotent after 0·5 h but after 4-h incubation IGF-I was 17-fold more potent, suggesting that this 'late' effect was mediated through the IGF-I receptor. Incubation with cycloheximide suggested that the effect of IGF-I involved increased protein synthesis. The results suggest that chicken myotubes express a glucose transporter which is regulated by IGF-I and glucose concentration. However, they do not appear to express a typical insulin-responsive transport system. Journal of Endocrinology (1993) 137, 465–472

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