Disease relevance of Igf1

• These data support the hypothesis that hypoxia regulation of IGFBP-1 may be a mechanism operating in the human fetus to restrict insulin-like growth factor-mediated growth in utero under conditions of chronic hypoxia and limited substrate availability [1].
• Insulin-like growth factor I is a comitogen for hepatocyte growth factor in a rat model of hepatocellular carcinoma [2].
• Hormonal regulation of insulin-like growth factor II and insulin-like growth factor binding protein expression by breast cancer cells in vivo: evidence for stromal epithelial interactions [3].
• The uterotrophic toxicity of chronic estradiol or tamoxifen treatment may be causally related to both the inhibition of uterine IGFBP-3 expression and the stimulation of uterine IGF-I expression by these compounds [4].
• In Rat 1 fibroblasts, stimulation of mitogen-activated protein (MAP) kinase via the IGF1 receptor and the Gi-coupled receptor for lysophosphatidic acid (LPA), but not via the EGF receptor, is sensitive both to pertussis toxin treatment and to cellular expression of a specific G beta gamma subunit-binding peptide [5].
• This work indicates that Akt, GSK-3beta, and beta-catenin probably contribute together to the IGF-I anti-atrophic effect in GC-induced muscle atrophy [6].

Psychiatry related information on Igf1

• We tested the hypothesis that low nephron number is already present during fetal development, and the expression pattern of important molecules of the IGF system is altered in MWF rat during the critical period of kidney development [7].
• In addition, alcohol consumption decreased IGF-I mRNA abundance in liver and muscle (approximately 50%) [8].
• The results indicate that high-amplitude pulses of GH were nearly abolished and that concentrations of GH, IGF-I, PRL, and leptin all were suppressed by sleep deprivation [9].
• IGF-I mRNA levels in the GH plus T group were not significantly different from those in the GH-treated group [10].
• We wondered: a) to what extent hypoxia effects on the GH-IGF-I axis differed from those of food deprivation alone; and b) whether administration of exogenous GH mitigates alterations of the GH-IGF-I axis caused by hypoxia or food restriction [11].

High impact information on Igf1

• Growth hormone and insulin act mainly by modulating the hepatic synthesis of IGF-I [12].
• IGF-I appears to mediate the effects of growth hormone on cartilage to promote skeletal growth whereas IGF-II may have a special role in fetal development and in the central nervous system [13].
• Prolactin-stimulated production of somatomedin by rat liver [14].
• Growth hormone and the insulin-like growth factor system in myogenesis [15].
• GH and IGF-I cause kidney growth, and circulating and/or renal IGF-I appear to contribute to renal hypertrophy and compensatory renal growth in experimental animal models [16].

Chemical compound and disease context of Igf1

• PURPOSE: In the present study, a recently described model of diabetic eye disease was used to investigate the distribution of the insulin-like growth factor (IGF) system in the eyes of transgenic (mRen-2)27 rats (exhibiting hypertension and elevated serum and ocular renin levels) with streptozotocin-induced diabetes [17].
• Double-stranded ribonucleic acid decreases C6 rat glioma cell numbers: effects on insulin-like growth factor I gene expression and action [18].
• While normalization of serum IGF-I levels does result in modest skeletal growth, selective organ growth and increased serum IGFBP-3, growth stimulation does not equal that seen with GH (body weight) or thyroid hormone (skeletal growth) [19].
• Genetic low nephron number hypertension is associated with dysregulation of the hepatic and renal insulin-like growth factor system during nephrogenesis [7].
• We investigated whether the prevention of glucocorticoid-induced muscle atrophy by glutamine infusion is associated with alterations in serum levels of insulin-like growth factor (IGF)-I and its binding proteins (IGFBPs) [20].

Biological context of Igf1

• Igf1 and Igfbp1 mRNA levels were upregulated during proliferative phase (Days 6-12) of rat gestation [21].
• Insulin-like growth factor I gene expression in isolated rat renal collecting duct is stimulated by epidermal growth factor [22].
• We have found that insulin-like growth factor I (IGF-I) can protect fibroblasts from apoptosis induced by UV-B light [23].
• The 24-kd IGFBP was found to comigrate with IGFBP-4, a recently identified binding protein that inhibits IGF action [24].
• IGF-I gene expression was highly dependent on cell density: IGF-I mRNA transcripts decreased markedly as a function of cell confluence [24].

Anatomical context of Igf1

• METHODS: The expression of the mammalian insulin-related genes (Ins, Igf1 and Igf2) was analysed in the thymus of inbred Wistar Furth rats (WF), diabetes-resistant BB (BBDR) and diabetes-prone BB (BBDP) rats [25].
• Insulin-like growth factor binding proteins from cultured human fibroblasts. Characterization and hormonal regulation [26].
• By multiple criteria, the species of IGF binding proteins produced by human fibroblasts are distinct from the HepG2/amniotic fluid IGF binding protein, but share many characteristics with the growth hormone-dependent IGF binding protein forms predominant in normal adult human plasma [26].
• Control smooth muscle cells or cells exposed to IGF-I alone did not have such effects.(ABSTRACT TRUNCATED AT 250 WORDS)[27]
• Insulin-like growth factor I inhibits induction of nitric oxide synthase in vascular smooth muscle cells [27].

Associations of Igf1 with chemical compounds

• In comparison, HepG2 IGF binding activity was enhanced by progesterone, decreased by insulin, and unaffected by growth hormone or glucocorticoid treatment [26].
• Two IGF-I-related proteins, IGF-II and insulin, also inhibited, but to a smaller extent, the release of nitrite and the formation of L-citrulline stimulated by IL-1 beta [27].
• This result is consistent with prior reports indicating that the uterotrophic effects of estradiol are mediated at least in part by estradiol-stimulated uterine IGF-I gene expression [4].
• The tyrosine 950 residue and serines 1280-1283 in the COOH terminus of the receptor are required for IGF-I-induced differentiation at 39 degrees C, although they are dispensable for IGF-I-mediated growth at 34 degrees C. Both domains have to be mutated to inactivate the differentiating function [28].
• The early renal growth in streptozotocin (STZ)-induced diabetic rats is preceded by a transient rise in renal tissue insulin-like growth factor (IGF)-I concentration [29].
• IGF-1 protected OPCs from TNFalpha cytotoxicity in a dose-dependent manner as measured by the XTT and TUNEL assays [30].

Physical interactions of Igf1

• The experiments reported herein were conducted to determine how corticosterone regulates growth and plasma insulin-like growth factor (IGF) I and IGF-binding protein (IGFBP) concentrations in normal and streptozotocin (STZ)-induced diabetic rats [31].
• Distinct sites of insulin-like growth factor (IGF)-II expression and localization in lesioned rat brain: possible roles of IGF binding proteins (IGFBPs) in the mediation of IGF-II activity [32].
• We show in this study that insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) accumulates to high levels in culture medium of growth-arrested type 2 cells [33].
• This indicates that glycosylation of IGFBP-4 does not affect its binding to IGF-I [34].
• The purpose of this work was to study the effect of insulin-like growth factor 1 (IGF-1) and its binding protein (IGFBP-3) on the recovery of erectile function in a rat model for neurogenic impotence [35].

Enzymatic interactions of Igf1

• However, EtOH attenuated the ability of IGF-I to phosphorylate ribosomal S6 kinase (S6K)-1 on residues T389 ( approximately 62%) and T421/S424 ( approximately 40%), and also reduced ribosomal protein S6 phosphorylation [36].
• By comparison, IGF-I increased the levels of the phosphorylated forms of ERK-1 and -2, and Akt/PKB [37].
• These data demonstrate that phosphorylation of IRS-1 plays an essential role in IGF-I and insulin signaling in oocyte maturation and that this effect occurs through interactions of the phosphorylated YMXM/YXXM motifs of IRS-1 with SH2 domains of PtdIns 3-kinase or some related molecules [38].
• Muscle levels of IGF-I mRNA and phosphorylated Akt were markedly reduced in ND animals with no change following anti-TNF-alpha therapy [39].
• Glutamate induces loss of sensitivity to IGF-I by phosphorylating the IGF-I receptor docking protein insulin-receptor-substrate (IRS)-1 in Ser(307) through a pathway involving activation of PKA and PKC in a hierarchical fashion [40].

Regulatory relationships of Igf1

• We hypothesized that IGF-I may play a role in regulating HGF-SF activity and HCC progression [2].
• Conversely, such negative regulation was silent in dedifferentiated VSMCs, where IGF-I activated both MAPKs via IRS-1/Grb2/Sos interaction-linked Ras activation, leading to proliferation and migration [41].
• These results suggest that IGF-I gene expression is down-regulated by Poly(IC) treatment and that IGF-I bioavailability and action in C6 cells are also altered due to decreases in IGF-I receptor and binding protein levels [18].
• Therefore, GH is able to activate the IGF-I/IGFBP-3 system in these cerebral cells and induce a physiological action of IGF-I [42].
• IGF-I promotes SC survival and protects IGFBP-5 in SC-conditioned medium from proteolysis [43].

Other interactions of Igf1

• Antiapoptotic signalling by the IGF-I receptor depended on receptor kinase activity, as cells overexpressing kinase-defective receptor mutants could not be protected by IGF-I [23].
• IGF-I also evoked a concentration-dependent increase in the abundance of IGFBP-3 in confluent, but not sparse, SMCs without affecting IGFBP-3 mRNA [44].
• The insulin-like growth factor, multiplication stimulating activity (MSA), and insulin were recently shown to stimulate proteoglycan synthesis in monolayer cultures of chondrocytes derived from the Swarm rat chondrosarcoma [45].
• IGFBP-5, the most conserved of six IGFBPs characterized to date, uniquely potentiates the anabolic actions of IGF-I for skeletal cells [46].
• Plasma IGFBP-2 was elevated and IGF-I was reduced in the nondiabetic Ax rats compared with sham Ax controls, but plasma IGFBP-3 and -4 were not significantly changed [31].

Analytical, diagnostic and therapeutic context of Igf1

• RESULTS: RT-PCR analyses of total RNA from WF, BBDP and BBDR thymi revealed that Igf1 and Ins mRNAs are present in 15/15 thymi from 2-day-old, 5-day-old and 5-week-old WF, BBDR and BBDP rats [25].
• The protease does not affect the structure of IGF-I as determined by reverse-phase high-performance liquid chromatography and size-exclusion chromatography of 125I-IGF-I incubated for up to 24 hours with SMC-conditioned medium containing IGFBP-4 [44].
• IGF-I stimulated chromogranin A gene expression by Northern blot analysis 3.7-fold [47].
• Combining these mutations in both domains (N+C-Term mutant) has a cumulative effect and leads to a 126-fold reduction in IGF-I binding as measured by biosensor [48].
• Because of the physiologic importance of IGF-I and its potential therapeutic properties, the renal sites of mRNA synthesis for IGF-I, IGF-IR, and IGFBP-I through IGFBP-5 were characterized in rat kidney by in situ hybridization [49].

References