Disease relevance of Igfbp1

• Cell culture studies show that cytokines exert direct effects on the production of IGFBP-1 by HepG2 hepatoma cells, increasing IGFBP-1 levels in conditioned medium and the abundance of IGFBP-1 mRNA approximately 3-fold [1].
• Transgenic mice that overexpressed IGFBP-1 are hyperinsulinemic in the first week of life and gradually develop fasting hyperglycemia [2].
• Evidence indicates that elevated levels of IGF-I with concomitant lowering of IGF binding protein (IGFBP)-3 are associated with increased risk for prostate cancer development and progression [3].
• The role of insulin-like growth factor-binding protein (IGFBP)-5 in human breast cancer cell growth is unclear [4].
• In addition, induction was seen for several genes not yet recognized to be involved in liver fibrosis, such as insulin-like growth factor-binding proteins (IGFBP) and antagonists of bone morphogenic proteins: follistatin and gremlin [5].

Psychiatry related information on Igfbp1

• Food deprivation resulted in increased levels of mouse IGFBP-1 mRNA but the total IGFBP-1 mRNA levels were not significantly different in Tg and Wt mice [6].

High impact information on Igfbp1

• Both MMP-9 and TGF-beta1 expression were suppressed by IGFBP-1 treatment, supporting their role in the apoptotic process [7].
• Within 3 hours of Fas agonist treatment, elevated expression of active TGF-beta1, a hepatocyte apoptogen, was observed in IGFBP-1-deficient livers that correlated with the appearance of the apoptotic process [7].
• Massive hepatic apoptosis associated with TGF-beta1 activation after Fas ligand treatment of IGF binding protein-1-deficient mice [7].
• IGF binding protein-1 (IGFBP-1), a hepatocyte-derived secreted protein, is required for normal liver regeneration [7].
• These data suggest that overexpression of IGFBP-1 attenuates the hypoglycemic effect of endogenous IGF-I, which is initially compensated for by enhanced pancreatic insulin production [2].

Chemical compound and disease context of Igfbp1

• Polyethylene glycol conjugated insulin-like growth factor binding protein-1 (IGFBP-1) inhibits growth of breast cancer in athymic mice [8].
• Hyperglycemia and impaired glucose tolerance in IGF binding protein-1 transgenic mice [9].

Biological context of Igfbp1

• Igfbp1 and 3 are found in the proximal part of chromosome 1 [10].
• Thus, despite only modest changes in IGF and IGFBP concentrations, the Igfbp5-overexpressing mice displayed a phenotype more extreme than that observed for other Igfbp genetic models [11].
• IGFBP mRNA and protein abundances were unaffected by genotype [12].
• PAPPA2, an enzyme that cleaves an insulin-like growth-factor-binding protein, is a candidate gene for a quantitative trait locus affecting body size in mice [13].
• This occurred without a change in IGF-I binding sites, suggesting a role for IGF binding protein (IGFBP) [14].

Anatomical context of Igfbp1

• Regulation of insulin-like growth factor binding protein secretion by a murine mammary epithelial cell line [15].
• Using two in vitro models, primary mouse preadipocytes and the 3T3-L1 preadipocyte cell line stimulated to differentiate with IGF-I, we studied IGF and IGFBP expression before and during differentiation [16].
• The goal of these studies was to determine the patterns and levels of IGFBP expression during postnatal growth of the murine mammary gland [17].
• Characterization of insulin-like growth factor binding proteins (IGFBP) and regulation of IGFBP-4 in bone marrow stromal cells [18].
• There were no differences in abundance between control and dexamethasone-treated ileum with regard to mRNA localization or abundance for IGFBP-1, -2, -3, and -6 [19].

Associations of Igfbp1 with chemical compounds

• Three lactogenic hormones (insulin, 154 nM; prolactin, 4.3 nM; and cortisol, 1.4 microM) in all combinations were tested to determine their effects on IGFBP secretion [15].
• Strikingly different patterns of IGFBP immunolocalization were observed between control and dexamethasone-treated animals [19].
• Here we examine IGFBP expression during regression of androgen-dependent Shionogi carcinoma tumors after castration [20].
• Insulin-like growth factor binding proteins (IGFBPs) -3 and -5 are known to interact with various components of the extracellular matrix (ECM; e.g. heparin and heparan sulphate) and this interaction is believed to affect the affinity of both IGFBP species for their cognate ligands--IGF-I and -II [21].
• In general, these data support the prediction made that chronically elevated exposure to IGF-I in IGF-I transgenic mice renders them less susceptible to the effects of ethanol than their non-transgenic siblings, and that overexpression of IGF binding protein 1 has the opposite effect [22].

Physical interactions of Igfbp1

• The IGF binding proteins (IGFBP's) showed weak mRNA expression for IGFBP-1 and -6 [23].

Enzymatic interactions of Igfbp1

• These findings have functional significance since alpha(2)M protects IGFBP-1 from proteolysis and abrogates the inhibitory effect of phosphorylated IGFBP-1 on IGF-I stimulated 3T3-L1 cell proliferation [24].

Regulatory relationships of Igfbp1

• Thus, variations in local IGF-I levels do not appear to regulate muscle IGFBP expression [12].
• Circulating IGFBP protease activity was induced in male PPARalpha-/- mice during refeeding [25].
• In conclusion we have shown that transformation of 3T3 cells with Ha-ras induced the synthesis of a new IGF binding protein in medium conditioned by normal 3T3 cells [26].
• IGFBP-1 inhibits EGF mitogenic activity in cultured endometrial stromal cells [27].
• Furthermore, the effect of conditioned medium on Akt phosphorylation could be inhibited by either LY-294002 or IGF-binding protein [28].

Other interactions of Igfbp1

• We have shown that all the genes studied, IGF-I, IGF-II, IGF receptor (IGFR) and IGF-binding protein (IGFBP)-1 to -6, were expressed in every stage, albeit at greatly differing levels and displaying unique expression profiles between developmental stages [29].
• Also, renal IGFBP-3 mRNA levels remained unchanged in most GHRA administration groups, whereas IGFBP-1, -4 and -5 mRNA levels were significantly increased in the 5 and 10 mg/kg/day GHRA administration groups [30].
• IGFBP-1 and insulin concentrations were higher in males than females, and were increased by PPARalpha knockout, suggesting significant hepatic insulin resistance [25].
• Northern blotting confirms that hepatic IGFBP-1 mRNA abundance also is increased acutely in both IL-1 alpha- and TNF alpha-treated animals [1].
• The regulation of insulin-like growth factor binding protein (IGFBP) secretion by mammogenic and lactogenic hormones was investigated in a mouse mammary epithelial cell line (COMMA-D/MME) [15].

Analytical, diagnostic and therapeutic context of Igfbp1

• IGFBP-1 to -5 proteins were detected in mammary tissue by immunoblotting during both pubertal and pregnancy-induced growth; however, the regulation of each IGFBP was distinct through these developmental periods [17].
• Tissue sections of ileum from both treatment conditions were processed in parallel for immunolocalization of each of the six IGFBP peptides and for in situ hybridization of each of the six IGFBP transcripts [19].
• Western ligand blotting and immunoprecipitation with specific antisera revealed that serum levels of IGFBP-1 (but not IGFBP-2, -3, -4, -5 or -6) are increased approximately 4 fold 2 h after treatment and then decline [1].
• Electrical stimulation modulates IGF binding protein transcript levels in C2C12 myotubes [31].
• Additionally, an IGFBP of approximately 27 K appeared during gestation; after treatment with Endoglycosidase F, this IGFBP decreased to 24 K [32].

References