HUGO ID Detailed Result 5464


HUGO ID 5464
Symbol IGF1
Name insulin-like growth factor 1 (somatomedin C)
#Occurrence 198
#Paper 8

 


PMID Match String Actual String Score Flanking text Edited by Edit
11173059IGF1IGF-11.2ciliary neurotrophic factor (CNTF), CNTF and insulin-like growth factor-1 (IGF-1) IGF-1 enhance motor neuron survival in vitro and can also exert 
15572176IGF1IGF-10.3SOD-1 mice expressing increased levels of insulin growth factor-1 (IGF-1) IGF-1 in spinal motor neurons and skeletal muscle 67 
15572176IGF1IGF-10.3whether these effects are due to an increased release of IGF-1 to the surrounding neuropil targeting glial cells or to a 
15657392IGF1Igf-13.5Muscle-specific expression of local Igf-1 (mIgf-1) mIgf-1 isoform also stabilized neuromuscular junctions reduced inflammation in 
15657392IGF1Igf-13.5acidic protein Igf insulin-like growth factor mIgf-1 local isoform of Igf-1 MyHC myosin heavy chain SOD1 superoxide dismutase1 wt wild-type 
15657392IGF1Igf-13.5Among these insulin-like growth factor 1 (Igf-1) Igf-1 has been implicated in anabolism of muscle and nerve tissues 
15657392IGF1Igf-13.5SOD1 mutant mouse muscle with an adeno-associated virus carrying an Igf-1 gene prolonged life and delayed disease progression ( Kaspar et 
15657392IGF1Igf-13.5However it is not clear from that study which Igf-1 isoform was used or whether the effects of Igf-1 expressed 
15657392IGF1Igf-13.5which Igf-1 isoform was used or whether the effects of Igf-1 expressed in motor neurons were cell autonomous 
15657392IGF1Igf-13.5Two major isoforms of Igf-1 originating from alternative splicing have been described differing in structure 
15657392IGF1Igf-13.5as circulating (class class 2 and local (class class 1 Igf-1 
15657392IGF1Igf-13.5Igf-1 class 2 transcripts predominate in the liver are highly growth 
15657392IGF1Igf-13.5The contribution to more localized accumulation of Igf-1 class 1 seems due to the combination of exon 1 
15657392IGF1Igf-13.5To assess the effects of supplemental Igf-1 directly on atrophic SOD1 skeletal muscle we exploited a transgenic 
15657392IGF1Igf-13.5mouse expressing a full-length precursor of the local isoform of Igf-1 (mIgf-1) mIgf-1 that is normally induced transiently in response to 
15657392IGF1Igf-13.5autocrine paracrine manner circumventing the adverse side effects of systemic Igf-1 administration 
15657392IGF1Igf-13.5attenuation of motor neuronal degradation and underscore the importance of Igf-1 isoform selection when designing therapeutic strategies for ALS 
15657392IGF1Igf-13.5mIgf-1 or indirect action either through distal activation of endogenous Igf-1 expression or through other trophic factors secreted by SOD /mIgf-1 
15657392IGF1Igf-13.5The Igf-1 cDNA used by Kaspar et al 
15657392IGF1Igf-13.5The importance of Igf-1 isoform choice in designing therapeutic strategies cannot be overstressed because 
15657392IGF1Igf-13.5Organization of the Igf-1 gene 
15657392IGF1Igf-13.5As its name implies Igf-1 is similar to insulin in structure 
15657392IGF1Igf-13.5The mature Igf-1 is a single-chain protein of 70 aa and differs from 
15657392IGF1Igf-13.5The rodent Igf-1 gene contains six exons separated by five introns (Fig Fig 
15657392IGF1Igf-13.5to all isoforms as well as part of the mature Igf-1 peptide 
15657392IGF1Igf-13.5region of the E-peptide which is also common to all Igf-1 mRNAs 
16877542IGF1IGF12.0products damage proteins such as insulin-like growth factor 1 (IGF1) IGF1 receptors which are located on motor neurons 
16877542IGF1IGF12.0data indicate that such an oxidative modification hinders the IGF1/Akt IGF1 Akt survival pathway in motor neurons 
16877542IGF1IGF12.0Phosphorylation of Akt and cell viability in response to IGF1 recombinant and to H 2 O 2 or activated BV2 
16877542IGF1IGF12.0NADPH Oxidase Impairs the Insulin-Like Growth Factor 1 (IGF1)/Akt IGF1 Akt Pathway in Transgenic SOD1 G93A Mice 
16877542IGF1IGF12.0by damaging essential surviving pathways for motor neurons such as IGF1 
16877542IGF1IGF12.0After IGF1 was immunoprecipitated from spinal cord extracts it was probed for 
16877542IGF1IGF12.0This approach failed to reveal evidence of IGF1 oxidation in any of the studied mouse genotypes (data data 
16877542IGF1IGF12.0carbonyl adducts were evident in the _amp_#x003b1 -chain of the IGF1 tyrosine kinase cognate receptor in the spinal cord of symptomatic 
16877542IGF1IGF12.0B similar results were obtained for the _amp_#x003b2 -chain of IGF1 receptor (data data not shown 
16877542IGF1IGF12.0This finding might be quite significant because IGF1 receptors in mouse spinal cords were detected almost exclusively on 
16877542IGF1IGF12.0Contrasting with the IGF1 receptor findings oxidation indices in the intracellular serine/threonine serine threonine 
16877542IGF1IGF12.0in the intracellular serine/threonine serine threonine kinase Akt which transduces IGF1 receptor signaling ( 15 did not differ between symptomatic transgenic 
16877542IGF1IGF12.0These results suggest that the entire IGF1 molecular pathway is not oxidatively modified by inflammation in this 
16877542IGF1IGF12.0Next we compared selected IGF1 transduction events among the different mouse groups 
16877542IGF1IGF12.0Although mutant SOD1 is expressed in all cells markers of IGF1 transduction such as phospho-IGF1 receptor phospho-Akt (data data not shown 
16877542IGF1IGF12.0These data further support the idea that oxidative modification of IGF1 receptor in symptomatic transgenic SOD1 G93A /gp91 gp91 phox mice 
16877542IGF1IGF12.0Microglial-Derived ROS Recapitulate the IGF1/Akt IGF1 Akt Pathway Defect in Vitro 
16877542IGF1IGF12.0To test the idea that NADPH oxidase-derived ROS could impair IGF1 pathway function an in vitro cell system using the neuron-like 
16877542IGF1IGF12.0were briefly incubated with 0.1_amp_#x02013 100 _amp_#x003bc M human recombinant IGF1 in the presence of overnight-preconditioned serum-free medium supplemented with or 
16877542IGF1IGF12.0to provide a constant flux of H 2 O 2 IGF1 pathway responsiveness was monitored by Akt phosphorylation 
16877542IGF1IGF12.0Exposure to IGF1 caused a dose-dependent phosphorylation of Akt in SH-SY5Y cells ( 
16877542IGF1IGF12.0Conversely IGF1 barely increased Akt phosphorylation in the neuroblastoma cell lines that 
16877542IGF1IGF1-mediated1.5of H 2 O 2 ( Fig 5 E attenuated IGF1-mediated Akt phosphorylation in the neuroblastoma cell line ( Fig 5 
16877542IGF1IGF12.0to LPS-activated microglial-conditioned medium the Akt phosphorylation response to the IGF1 recombinant remained depressed and at 72 h a reduction of 
16877542IGF1IGF12.0a reduction of cell viability indistinguishable from the condition without IGF1 was observed ( Fig 5 F 
16877542IGF1IGF1-mediated1.5However both the alteration of IGF1-mediated Akt phosphorylation and the loss of cell viability mediated by 
16877542IGF1IGF12.0Relevant to the latter scenario are our results for IGF1 a trophic factor that is known to promote motor neuron 
16877542IGF1IGF12.0In this study we indeed found that receptors for IGF1 were primarily expressed on motor neurons in mouse spinal cords 
16877542IGF1IGF12.0in mouse spinal cords (Fig Fig 8 and that the IGF1 signaling pathway was impaired by a NADPH oxidase-dependent mechanism in 
16877542IGF1IGF12.0Although IGF1 per se did not seem to be damaged by inflammation 
16877542IGF1IGF12.0by inflammation NADPH oxidase did stimulate the oxidative modification of IGF1 receptors ( Fig 4 
16877542IGF1IGF12.0The ligand-dependent kinase activation of IGF1 receptor relies on its arrangement into a heterotetrameric 2_amp_#x003b1;/2_amp_#x003b2;-chain 2_amp_#x003b1 
16877542IGF1IGF12.0It may thus be predicted that oxidation of the IGF1 receptor main extracellular domains (i.e., i.e. the _amp_#x003b1 -chains could 
16877542IGF1IGF12.0molecular events that are normally elicited by ligation of the IGF1 receptor including autophosphorylation and Akt phosphorylation were indeed abated by 
16877542IGF1IGF12.0data also show that microglial NADPH oxidase by impairing the IGF1 signaling pathway renders SH-SY5Y cells in our in vitro system 
16877542IGF1IGF12.0Muscle-specific expression of IGF1 stabilizes neuromuscular junctions reduces inflammation in the spinal cord and 
16877542IGF1IGF12.0did not find any evidence that the rescue of the IGF1 pathway by abrogating NADPH oxidase was associated with muscle hypertrophy 
16877542IGF1IGF12.0transgenic SOD1 G93A mice with an adeno-associated virus carrying an IGF1 gene prolongs survival in these animals ( 20 24 
16877542IGF1IGF12.0but instead may blunt the motor neuron survival response to IGF1 in ALS 
16877542IGF1IGF12.0progression that is seen in patients treated with human recombinant IGF1 ( 25 may be related to the issue raised above 
16877542IGF1IGF12.0It may thus be argued that optimal therapeutic response to IGF1 in diseases such as ALS may rely on a concomitant 
16877542IGF1IGF12.0Modulation of the IGF1/Akt IGF1 Akt pathway by NADPH oxidase-derived ROS 
16877542IGF1IGF12.0( A Immunoprecipitation of IGF1 receptor _amp_#x003b1 -chain followed by OxyBlot (upper upper blot and 
16877542IGF1IGF12.0by OxyBlot (upper upper blot and immunoblot for spinal cord IGF1 receptor _amp_#x003b1 -chain (lower lower blot 
16877542IGF1IGF12.0Glucose oxidase- and microglial-derived ROS impair the IGF1 Akt pathway in vitro 
16877542IGF1IGF1-treated1.5upper blot and total Akt (lower lower blot immunoblots of IGF1-treated SH-SY5Y cells exposed or not exposed to 75 _amp_#x003bc M 
16877542IGF1IGF12.0ROS reactive oxygen species SOD1 superoxide dismutase 1 IGF1 insulin-like growth factor 1 
17015226IGF1IGF-11.2hypertrophy induced by agents such as insulin-like growth factor-1 (IGF-1) IGF-1 or growth hormone ( Dobrowolny et_amp_#xa0 al. 2005 Kaspar et_amp_#xa0 
17015226IGF1IGF-11.2For the IGF-1 studies not only was there muscle hypertrophy but also concomitant 
17015226IGF1IGF-11.2Although in one instance IGF-1 synthesis was mediated by a transgene expressed only by the 
17015226IGF1IGF-11.2al. 2005 it has not been established if the secreted IGF-1 acts on the muscle the motor neuron or both 
17015226IGF1IGF-11.2al. 2003 and Veldink et_amp_#xa0 al. 2003 with_amp_#xa0 exercise and IGF-1 exhibiting a synergistic effect resulting in an increase in median 
17015226IGF1IGF-11.2to nearly uniform disappointment providing little or no benefit for IGF-1 ( Borasio et_amp_#xa0 al. 1998 and Lai et_amp_#xa0 al. 1997 
17015226IGF1IGF-11.2was found to be without benefit but ICV infusion of IGF-1 extended survival in mice ( Nagano et_amp_#xa0 al. 2005a and 
17015226IGF1IGF-11.2precursors including those engineered to produce trophic factors such as IGF-1 are now sensible approaches 
17018025IGF1IGF-13.5O 2 _amp_middot _amp_#8722 and decreased insulin-like growth factor-1 (IGF-1) IGF-1 release from microglial cultures and induced motoneuron injury in microglia-motoneuron 
17018025IGF1IGF-13.5Although IL-4 enhanced release of free IGF-1 from microglia in the absence of lipopolysaccharide it did not 
17018025IGF1IGF-13.5in the absence of lipopolysaccharide it did not enhance free IGF-1 release in the presence of lipopolysaccharide 
17018025IGF1IGF-13.5of TNF-A and up-regulation of insulin-like growth factor 1 (IGF-1) IGF-1 from microglia ( Butovsky et al 2005 2006 
17018025IGF1IGF-13.5release more nitric oxide and and lower levels of free IGF-1 an active form of the neurotrophic factor 
17018025IGF1IGF-13.5This anti-inflammatory cytokine also enhanced free IGF-1 without lipopolysaccharide stimulation 
17018025IGF1IGF-13.5However with lipopolysaccharide there was a minimal increase in free IGF-1 yet the cytokine was still neuroprotective 
17018025IGF1IGF-13.5ELISA for free IGF-1 IGF-1 ELISA Duoset kit (R R _amp_ D Systems Minneapolis 
17018025IGF1IGF-13.5ELISA for free IGF-1 IGF-1 ELISA Duoset kit (R R _amp_ D Systems Minneapolis MN 
17018025IGF1IGF-13.5MN USA was used to determine the concentration of free IGF-1 protein in cell culture supernatant 
17018025IGF1IGF-13.5h 100 _amp_#x03BC L of either sample or standard rat IGF-1 (Diagnostic Diagnostic Systems Laboratories Webster TX USA was added to 
17018025IGF1IGF-13.5Lipopolysaccharide-activated microglia increased production of nitric oxide and decreased free IGF-1 In our previous study we demonstrated that nitric oxide plays 
17018025IGF1IGF-13.5In the present experiments levels of free IGF-1 as well as nitric oxide were measured in microglia activated 
17018025IGF1IGF-13.5We also assayed the levels of free IGF-1 in microglia cultures given that only free IGF-1 is active 
17018025IGF1IGF-13.5of free IGF-1 in microglia cultures given that only free IGF-1 is active 
17018025IGF1IGF-13.5the presence of 1 _amp_#x03BC;g/mL _amp_#x03BC g mL lipopolysaccharide free IGF-1 concentrations were significantly lower than untreated microglia ( Fig 1b 
17018025IGF1IGF-13.5In MN Mc cocultures lipopolysaccharide decreased free IGF-1 in a dose-dependent manner ( Fig 2b 
17018025IGF1IGF-13.5m MN lipopolysaccharide 1.02 _amp_plusmn 0.10 _amp_#x03BC m and free IGF-1 levels (MN MN only 1.95 _amp_plusmn 0.31 pg/mL, pg mL 
17018025IGF1IGF-13.5were all close to background indicating that nitrite nitrate and IGF-1 were produced by microglia 
17018025IGF1IGF-13.5Free IGF-1 did not increase after addition of IL-4 to lipopolysaccharide-activated microglia 
17018025IGF1IGF-13.5to lipopolysaccharide-activated microglia In Fig 1b we noted less free IGF-1 in the culture media following microglial activation with lipopolysaccharide 
17018025IGF1IGF-13.5To determine whether IGF-1 production was influenced by IL-4 the levels of free IGF-1 
17018025IGF1IGF-13.5IGF-1 production was influenced by IL-4 the levels of free IGF-1 were measured in microglia monocultures or MN Mc cocultures 
17018025IGF1IGF-13.5In cultures without lipopolysaccharide IL-4 significantly increased levels of free IGF-1 ( Fig 9a b 
17018025IGF1IGF-13.5The free IGF-1 of motoneuron only cultures were close to background level in 
17018025IGF1IGF-13.5indicating that microglia were the source of the increased free IGF-1 after IL-4 treatment 
17018025IGF1IGF-13.5However the levels of free IGF-1 did not change significantly in lipopolysaccharide-activated microglia or in MN 
17018025IGF1IGF-13.5Similar results were seen when IGF-1 mRNA levels were measured with and without IL-4 (data data 
17018025IGF1IGF-13.5finding in the current study is that IL-4 increased free IGF-1 the active form of this neuroprotective factor in untreated microglia 
17018025IGF1IGF-13.5factor in untreated microglia cultures and that lipopolysaccharide decreased free IGF-1 
17018025IGF1IGF-13.5At first we hypothesized that the induction of free IGF-1 in microglia might be another aspect of IL-4 neuroprotection however 
17018025IGF1IGF-13.5lipopolysaccharide-treated MN Mc cocultures however IL-4 did not increase free IGF-1 levels in the same cocultures 
17018025IGF1IGF-13.5In addition we saw no increase in IGF-1 mRNA in these lipopolysaccharide-activated cultures although it has been reported 
17018025IGF1IGF-13.5lipopolysaccharide-activated cultures although it has been reported that IL-4 up-regulated IGF-1 mRNA in both untreated and lipopolysaccharide-activated microglia ( Butovsky et 
17018025IGF1IGF-13.5Additionally even though free IGF-1 was up-regulated by IL-4 in untreated microglia cocultured with motoneurons 
17018025IGF1IGF-13.5Finally we also found a poor correlation between free IGF-1 levels and motoneuron survival in MN Mc cocultures 
17018025IGF1IGF-13.5Therefore these results suggest that IGF-1 may not be the primary mechanism of IL-4 neuroprotection 
17018025IGF1IGF-13.5Firstly IGF-1 is clearly a generally neuroprotective trophic factor that has been 
17018025IGF1IGF-13.5that there may have been an immediate local increase in IGF-1 that was quickly sequestered by binding proteins it is likely 
17018025IGF1IGF-13.5sequestered by binding proteins it is likely that the free IGF-1 levels induced by IL-4 either before or after lipopolysaccharide in 
17018025IGF1IGF-13.5Secondly because free IGF-1 levels are determined by total IGF-1 and the levels of 
17018025IGF1IGF-13.5Secondly because free IGF-1 levels are determined by total IGF-1 and the levels of the five known binding proteins ( 
17018025IGF1IGF-13.5et al 2005 there may have been increases in both IGF-1 and one or more of the binding proteins that resulted 
17018025IGF1IGF-13.5binding proteins that resulted in no net change in free IGF-1 
17018025IGF1IGF-13.5Finally it is possible that neurotrophic factors other than IGF-1 may enhance the neuroprotective actions of this anti-inflammatory cytokine 
17018025IGF1IGF-13.5free radicals released from microglia and may not involve free IGF-1 
17018025IGF1IGF-13.5IL-10 increased microglial release and also decreased rather than increased IGF-1 release from microglia (data data not shown 
17555556IGF1IGF-11.2nitric oxide more superoxide and less insulin-like growth factor-1 (IGF-1) IGF-1 than wild-type microglia 
17555556IGF1IGF-11.2The supernatants were collected for nitric oxide and IGF-1 assays and the cells were collected for western analyses 
17555556IGF1IGF-11.2supernatants of the co-cultures were collected for nitric oxide and IGF-1 assays and the cells on the coverslips were fixed with 
17555556IGF1IGF-11.2ELISA for IGF-1 Insulin-like growth factor-1 ELISA Duoset kit (R R _amp_ D 
17555556IGF1IGF-11.2Minneapolis MN USA was used to determine the concentrations of IGF-1 in cell culture supernatants 
17555556IGF1IGF-11.2the addition of 100 _amp_#x03BC L of samples or mouse IGF-1 standard and incubated for 2 h at 22_amp_deg C 
17555556IGF1IGF-11.2Mutant SOD1 G93A microglia produce more neurotoxins and less IGF-1 than wild-type microglia 
17555556IGF1IGF-11.2other previous studies demonstrated that microglia produce significant amounts of IGF-1 ( Butovsky et al 2005 Zhao et al 2006 we 
17555556IGF1IGF-11.22005 Zhao et al 2006 we measured the presence of IGF-1 in the supernatants of the untreated and LPS-treated microglia cultures 
17555556IGF1IGF-11.2There was 1100 _amp_plusmn 180 pg/mL pg mL IGF-1 in the untreated wild-type microglia supernatants which was set at 
17555556IGF1IGF-11.2Untreated mSOD1 G93A microglia released 22% less IGF-1 compared with untreated wild-type microglia ( p _lt_ 0.01 ( 
17555556IGF1IGF-11.2with 10 or 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS less IGF-1 was measured in both wild-type and mSOD1 G93A microglia 
17555556IGF1IGF-11.2either concentrations of LPS mSOD1 G93A microglia released significantly less IGF-1 than wild-type microglia (10 10 ng/mL ng mL LPS 21 
17555556IGF1IGF-11.22.4% from wild-type microglia a 22% decrease in production of IGF-1 p _lt_ 0.01 1 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS 18 
17555556IGF1IGF-11.22.2% in wild-type microglia a 22% decrease in production of IGF-1 p _lt_ 0.05 
17555556IGF1IGF-11.2treatment mSOD1 G93A microglia released significantly more superoxide and less IGF-1 than wild-type microglia suggesting that mSOD1 G93A microglia are more 
17555556IGF1IGF-11.2presence of 100 times less LPS although the amount of IGF-1 released was small mSOD1 G93A microglia did not release significantly 
17555556IGF1IGF-11.2was small mSOD1 G93A microglia did not release significantly more IGF-1 than wild-type microglia treated with 1 _amp_#x03BC;g/mL _amp_#x03BC g mL 
17555556IGF1IGF-11.2microglia co-cultured with motoneurons produce more nitric oxide and less IGF-1 than wild-type microglia Because we demonstrated that primary cultures of 
17555556IGF1IGF-11.2The IGF-1 levels in untreated mSOD1 G93A microglia/motoneuron microglia motoneuron co-cultures were 
17555556IGF1IGF-11.21 _amp_#x03BC;g/mL _amp_#x03BC g mL LPS both co-cultures released less IGF-1 (37 37 _amp_plusmn 2.1% in wild-type microglia and 26 _amp_plusmn 
17555556IGF1IGF-11.2However mSOD1 G93A microglia/motoneuron microglia motoneuron co-cultures released significantly less IGF-1 (30% 30% decrease than wild-type microglia/motoneuron microglia motoneuron co-cultures ( 
17555556IGF1IGF-11.2microglia co-cultured with motoneurons produced more nitric oxide and less IGF-1 than wild-type microglia we asked whether mSOD1 G93A microglia would 
17555556IGF1IGF-11.2not observe significant increase of nitric oxide superoxide or less IGF-1 from wt-hSOD1 microglia compared with their littermate controls ( Table 
17555556IGF1IGF-11.2Among these neurotrophic factors IGF-1 has been shown to have a protective effect on motoneurons 
17555556IGF1IGF-11.2IGF-1 is a potent neurotrophic and survival factor ( Vincent et 
17555556IGF1IGF-11.2In contrast free IGF-1 levels in ALS patients_amp_#8217 spinal cords and serum were shown 
17555556IGF1IGF-11.2al 1998 Wilczak et al 2003 suggesting that down-regulation of IGF-1 trophic support may lead to degeneration of motoneurons 
17555556IGF1IGF-11.2IGF-1 has been reported to prevent glutamate-induced embryonic rat spinal cord 
17555556IGF1IGF-11.2and delayed disease progression in transgenic ALS mice by enhancing IGF-1 expression in motoneurons 
17555556IGF1IGF-11.2A recent study showed that intrathecal injection of IGF-1 into the lumbar spinal cord of transgenic mice expressing the 
17555556IGF1IGF-11.2Following activation with LPS the current study demonstrated that free IGF-1 levels were significantly reduced to 20-30% of untreated controls 
17555556IGF1IGF-11.2represent the first demonstration that wild-type microglia released more free IGF-1 than microglia from mSOD1 G93A transgenic mice either with or 
17555556IGF1IGF-11.2Therefore more IGF-1 neurotrophic support from wild-type microglia may also contribute to the 
17555556IGF1IGF-11.2Additionally wild-type microglia may be more neuroprotective by secreting more IGF-1 compared to mSOD1 G93A microglia 
17555556IGF1IGF-11.2G93A microglia released more nitric oxide more superoxide and less IGF-1 
17555556IGF1IGF-11.2wt-hSOD1 microglia produce similar amounts of nitric oxide superoxide and IGF-1 compared with their wild-type littermates 
17555556IGF1IGF-11.2mice by producing more nitrite oxide and superoxide and less IGF-1 
11173059insulin-like growth factor 1insulin like growth factor 11.0neurotrophic factors such as brain derived neurotrophic factor bdnf ciliary neurotrophic factor cntf and insulin like growth factor 1 igf 1 enhance motor neuron survival in vitro and can also exert beneficial effects in mouse models of amyotrophic lateral sclerosis reviewed in yuen and mobley 1996 .  
11173059insulin-like growth factor 1insulin like growth factor 11.0brain derived neurotrophic factor levels are decreased in alzheimer disease hippocampi ferrer et al. 1999 and insulin like growth factor 1 shows protective effects against _amp_#x3b2; amyloid protein neurotoxicity dore et al. 1999 .  
12137643insulin like growth factorinsulin like growth factor1.0recombinant human insulin like growth factor i rhigf i for amyotrophic lateral sclerosis/motor neuron disease.  
12137643insulin like growth factorinsulin like growth factor1.0background: trophic factors including recombinant human insulin like growth factor i have been postulated as possible disease modifying therapies for amyotrophic lateral sclerosis.  
12137643insulin like growth factorinsulin like growth factor1.0randomised clinical trials of recombinant human insulin like growth factor i in amyotrophic lateral sclerosis to date have yielded conflicting results.  
12137643insulin like growth factorinsulin like growth factor1.0objectives: the main objective of this review was to examine the efficacy of recombinant human insulin like growth factor i in amyotrophic lateral sclerosis.  
12137643insulin like growth factorinsulin like growth factor1.0search strategy: a search was carried out using the cochrane neuromuscular disease group register for randomised clinical trials of recombinant human insulin like growth factor i in amyotrophic lateral sclerosis.  
12137643insulin like growth factorinsulin like growth factor1.0enquiries were also made of authors of randomised clinical trials as well as the manufacturers of recombinant human insulin like growth factor i regarding any other randomised clinical trials which had not yet been published.  
12137643insulin like growth factorinsulin like growth factor1.0selection criteria: types of studies: all randomised controlled clinical trials involving recombinant human insulin like growth factor i treatment of amyotrophic lateral sclerosis.  
12137643insulin like growth factorinsulin like growth factor1.0types of interventions: treatment with recombinant human insulin like growth factor i or placebo.  
12137643insulin like growth factorinsulin like growth factor1.0types of outcome measures: primary: change in appel amyotrophic lateral sclerosis rating scale aalsrs total score with 0.1mg/kg/day of recombinant human insulin like growth factor i after nine months treatment.  
12137643insulin like growth factorinsulin like growth factor1.0secondary: change in aalsrs with recombinant human insulin like growth factor i 0.1mg/kg/day and 0.05mg/kg/day at 1 2 3 4 5 6 7 8 9 months change in quality of life sickness impact profile scale survival and adverse events.  
12137643insulin like growth factorinsulin like growth factor1.0main results: the primary outcome measure was change in disease progression as determined by the appel als rating scale total score with 0.1 mg/kg/day of recombinant human insulin like growth factor i subcutaneously after nine months treatment.  
12137643insulin like growth factorinsulin like growth factor1.0the level of significance was lower in the european trial which compared 59 patients on placebo with 124 on insulin like growth factor i 0.1 mg/kg/day weighted mean difference 3.30 95%ci 8.68 to 2.08 than in the north american trial which compared 90 patients on placebo with 89 on recombinant human insulin like growth factor i 0.05  
12137643insulin like growth factorinsulin like growth factor1.0 i 0.1 mg/kg/day weighted mean difference 3.30 95%ci 8.68 to 2.08 than in the north american trial which compared 90 patients on placebo with 89 on recombinant human insulin like growth factor i 0.05 mg/kg/day 89 patients and 87 patients on 0.1mg/kg/day weighted mean difference 6.00 95%ci 10.99 to 1.01 .  
12137643insulin like growth factorinsulin like growth factor1.0the secondary outcome measures showed similar trends favouring recombinant human insulin like growth factor i but these did not reach significance at the five per cent level.  
12137643insulin like growth factorinsulin like growth factor1.0similarly the data with the 0.05mg/kg/day dose showed trends favouring recombinant human insulin like growth factor i at all time points but did not reach significance at the five per cent level at any point.  
12137643insulin like growth factorinsulin like growth factor1.0evaluation of adverse events showed an increased risk of injection site reactions/inflammation with recombinant human insulin like growth factor i relative risk 2.53 95% ci 1.40 to 4.59 .  
12137643insulin like growth factorinsulin like growth factor1.0reviewer's conclusions: recombinant human insulin like growth factor i may be modestly effective but the evidence currently available is insufficient for a definitive assessment.  
15657392insulin like growth factorinsulin like growth factor1.0here we show that muscle restricted expression of a localized insulin like growth factor igf 1 isoform maintained muscle integrity and enhanced satellite cell activity in sod1 transgenic mice inducing calcineurin mediated regenerative pathways.  
15657392insulin like growth factorinsulin like growth factor1.0abbreviations used in this paper: achr acetylcholine receptor; als amyotrophic lateral sclerosis; cna calcineurin; gfap glial fibrillary acidic protein; igf insulin like growth factor; migf 1 local isoform of igf 1; myhc myosin heavy chain; sod1 superoxide dismutase1; wt wild type.  
15657392insulin-like growth factor 1insulin like growth factor 11.0among these insulin like growth factor 1 igf 1 has been implicated in anabolism of muscle and nerve tissues inducing muscle hypertrophy and promoting neuronal survival musar_amp_ograve; and rosenthal 2002 .  
16877542insulin-like growth factor 1insulin like growth factor 11.0we also show that nadph oxidase derived oxidant products damage proteins such as insulin like growth factor 1 igf1 receptors which are located on motor neurons.  
16877542insulin-like growth factor 1insulin like growth factor 11.0nadph oxidase impairs the insulin like growth factor 1 igf1 /akt pathway in transgenic sod1 g93a mice.  
16877542insulin-like growth factor 1insulin like growth factor 11.0ros reactive oxygen species sod1 superoxide dismutase 1 igf1 insulin like growth factor 1  
17015226insulin-like growth factor 1insulin like growth factor 11.0on the other hand muscle hypertrophy induced by agents such as insulin like growth factor 1 igf 1 or growth hormone dobrowolny et_amp_#xa0;al. 2005 kaspar et_amp_#xa0;al. 2003 and kaspar et_amp_#xa0;al. 2005 has led to significant life extensions in als transgenic mice.  
17018025insulin-like growth factor 1insulin like growth factor 11.0tivated by lipopolysaccharide as well as to activated microglia cocultured with primary motoneurons. lipopolysaccharide increased nitric oxide and superoxide o 2 _amp_middot;_amp_#8722; and decreased insulin like growth factor 1 igf 1 release from microglial cultures and induced motoneuron injury in microglia motoneuron cocultures.  
17018025insulin-like growth factor 1insulin like growth factor 11.0recently it has been documented that protection of il 4 was attributed to down regulation of tnf a and up regulation of insulin like growth factor 1 igf 1 from microglia butovsky et al 2005 2006 .  
17555556insulin-like growth factor 1insulin like growth factor 11.0following activation with lipopolysaccharide msod1 g93a microglia released more nitric oxide more superoxide and less insulin like growth factor 1 than wild type microglia.  
17555556insulin-like growth factor 1insulin like growth factor 11.0our results demonstrate that msod1 g93a mouse microglia release more nitric oxide more superoxide and less insulin like growth factor 1 igf 1 than wild type microglia.  
17555556insulin-like growth factor 1insulin like growth factor 11.0elisa for igf 1 insulin like growth factor 1 elisa duoset kit r _amp_ d systems minneapolis mn usa was used to determine the concentrations of igf 1 in cell culture supernatants.  
17555556insulin-like growth factor 1insulin like growth factor 11.0insulin like growth factor 1 is a potent motoneuron trophic and survival factor.