Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have found that over one-half of the total cell surface 125I-insulin-like growth factor I (IGF-I) binding to BHK cells represents binding to IGF binding proteins (IGFBPs) rather than to the IGF-I receptor. In addition to a number of secreted IGFBPs, we have now characterized two cell-associated IGFBPs with unique characteristics. The cell-associated IGFBPs have molecular weights of 30,000 (30K) and 25,000 (25K), as determined by the Western ligand blot technique. IGFBP-30K is located at the cell surface and can be readily labeled by affinity cross-linking with 125I-IGF-I. Surface expression of IGFBP-30K increases 5.4 +/- 1.2-fold (n = 11) with serum starvation. This induction is fully evident by 4 h, plateauing by 24 h, and is completely inhibitable by cycloheximide. The fasting-induced increase in IGFBP-30K is inhibited by IGF-I and by des-IGF-I and, to a lesser extent, by insulin. Unlike cell-associated IGFBP-30K, secretion of IGFBP was stimulated (6.8 +/- 0.5-fold, n = 2) by IGF-I, whereas IGFBP secretion was inhibited 54% by insulin. These results demonstrate coordinate regulation of IGFBP by serum starvation and IGF-I, such that at low concentrations of IGF-I, cell surface binding protein increases whereas binding protein secretion decreases. At high concentrations of IGF-I, IGFBP secretion increases and cell surface IGF-I receptor, as well as IGFBP, decreases. Taken together, these regulatory events regulate the availability of IGF-I for biologic signalling.
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PMID:Characterization of insulin-like growth factor (IGF) binding proteins and their role in modulating IGF-I action in BHK cells. 128 Nov 61

Human breast cancer MCF-7 cells, growth-arrested by serum starvation, were stimulated with recombinant human insulin-like growth factor-I (IGF-I). An increase in DNA synthesis was induced 20 hr later, which was as effective as that induced by serum. The increase in DNA synthesis was significantly inhibited either by antibody to the IGF-I receptor or by the tyrosine kinase inhibitor, methyl-2,5-dihydroxycinnamate (2,5-MeC). The IGF-I-induced DNA synthesis coincided with an elevated level of phosphorylation of p53 on tyrosine and an alteration in the subcellular distribution of the protein from the nucleus to the cytoplasm. Whereas the increases in DNA synthesis and p53 phosphorylation were inhibited by antibody to the IGF-I receptor and by 2,5-Mec, the nuclear exclusion of p53 was prevented by the antibody and also, although not significantly, by 2,5-Mec. The results suggest that growth stimulation of MCF-7 cells by IGF-I is accompanied by tyrosine phosphorylation and nuclear exclusion of p53.
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PMID:Association of insulin-like growth-factor-I-induced DNA synthesis with phosphorylation and nuclear exclusion of p53 in human breast cancer MCF-7 cells. 837 29

Insulin-like growth factor-I (IGF-I) exerts its effect through the IGF-I receptor. To investigate the effects of nutritional status on chicken IGF-I receptor gene expression, a solution hybridization/RNase protection assay for IGF-I receptor mRNA was developed. A cDNA clone corresponding to the carboxyl-terminal region of the IGF-I receptor was obtained by reverse transcription-PCR (RT-PCR). Sequence analysis of the clone showed that this region of the chicken IGF-I receptor is highly divergent from the human IGF-I receptor. IGF-I receptor mRNA was detected in all tissues examined from newly hatched chickens. The rank order of the IGF-I receptor mRNA levels was liver < thigh muscle < stomach < heart < lung < kidney < brain. In 1-week-old chickens, 5 days of starvation caused a 2.5- to 3-fold increase in the mRNA in muscle and kidney. Starvation of 4-week-old chickens for 5 days caused a 1.7 to 2.2-fold increase in IGF-I receptor mRNA levels in kidney, liver, and muscle. In contrast, IGF-I receptor mRNA levels in brain failed to change. The mRNA levels were reduced to the control level by refeeding of the starved chickens for 24h. These data suggest a tissue- and development-specific response of chicken IGF-I receptor gene expression to nutritional status.
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PMID:Nutritional regulation of insulin-like growth factor-I receptor mRNA levels in growing chickens. 869 14

Insulin-like growth factor-I (IGF-I) receptors and insulin receptors belong to the same subfamily of receptor tyrosine kinases and share a similar set of intracellular signaling pathways, despite their distinct biological actions. In the present study, we evaluated T cell death-associated gene 51 (TDAG51), which we previously identified by cDNA microarray analysis as a gene specifically induced by IGF-I. We characterized the signaling pathways by which IGF-I induces TDAG51 gene expression and the functional role of TDAG51 in IGF-I signaling in NIH-3T3 (NWTb3) cells, which overexpress the human IGF-I receptor. Treatment with IGF-I increased TDAG51 mRNA and protein levels in NWTb3 cells. This effect of IGF-I was specifically mediated by the IGF-IR, because IGF-I did not induce TDAG51 expression in NIH-3T3 cells overexpressing a dominant-negative IGF-I receptor. Through the use of specific inhibitors of various protein kinases, we found that IGF-I induced TDAG51 expression via the p38 MAPK pathway. The ERK, JNK, and phosphatidylinositol 3-kinase pathways were not involved in IGF-I-induced regulation of TDAG51. To assess the role of TDAG51 in IGF-I signaling, we used small interfering RNA (siRNA) expression vectors directed at two different target sites to reduce the level of TDAG51 protein. In cells expressing these siRNA vectors, TDAG51 protein levels were decreased by 75-80%. Furthermore, TDAG51 siRNA expression abolished the ability of IGF-I to rescue cells from serum starvation-induced apoptosis. These findings suggest that TDAG51 plays an important role in the anti-apoptotic effects of IGF-I.
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PMID:TDAG51 mediates the effects of insulin-like growth factor I (IGF-I) on cell survival. 1503 19

The insulin-like signaling pathway is known to regulate fat metabolism, dauer formation, and longevity in Caenorhabditis elegans. Here, we report that this pathway is also involved in salt chemotaxis learning, in which animals previously exposed to a chemoattractive salt under starvation conditions start to show salt avoidance behavior. Mutants of ins-1, daf-2, age-1, pdk-1, and akt-1, which encode the homologs of insulin, insulin/IGF-I receptor, PI 3-kinase, phosphoinositide-dependent kinase, and Akt/PKB, respectively, show severe defects in salt chemotaxis learning. daf-2 and age-1 act in the ASER salt-sensing neuron, and the activity level of the DAF-2/AGE-1 pathway in this neuron determines the extent and orientation of salt chemotaxis. On the other hand, ins-1 acts in AIA interneurons, which receive direct synaptic inputs from sensory neurons and also send synaptic outputs to ASER. These results suggest that INS-1 secreted from AIA interneurons provides feedback to ASER to generate plasticity of chemotaxis.
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PMID:The insulin/PI 3-kinase pathway regulates salt chemotaxis learning in Caenorhabditis elegans. 1695 Jan 59

Insulin-like growth factor 1 receptor (IGF-1R) is critical for cancer cell proliferation; however, recent clinical anti-IGF-1R trials did not show clear clinical benefit in cancer therapy. We hypothesized that IGF-1R signaling-mediated proliferative response is heterogeneous in neuroblastoma (NB) cells, and analyzed the cell growth of 31 NB cell lines cultured in three different media, including Hybridoma-SFM medium (with insulin) and RPMI1640 with/without 10% FBS. Three growth patterns were found. In response to IGF and insulin, cell proliferation and Akt phosphorylation were upregulated in 13 cell lines, and suppressed by MK2206 (Akt inhibitor) and picropodophyllin (IGF-1R inhibitor). Interestingly, 3 of these 13 cell lines showed Akt self-phosphorylation and cell proliferation in RPMI1640; their proliferation was downregulated by anti-IGF-1 or anti-IGF-2 neutralizing antibody, suggesting the existence of an autocrine loop in the IGF-1R/Akt pathway. Eighteen NB cell lines did not proliferate in RPMI1640, even though Akt phosphorylation was upregulated by IGF and insulin. Based on the heterogeneous response of the IGF-1R/Akt pathway, the 31 NB cell lines could be classified into group 1 (autocrine IGF-mediated), group 2 (exogenous IGF-mediated) and group 3 (partially exogenous IGF-mediated) NB cell lines. In addition, group 3 NB cell lines were different from group 1 and 2, in terms of serum starvation-induced caspase 3 cleavage and picropodophyllin-induced G2/M arrest. These results indicate that the response of the IGF-1R/Akt pathway is an important determinant of the sensitivity to IGF-1R antagonists in NB. To our knowledge, this is the first report describing heterogeneity in the IGF-1R/Akt-mediated proliferation of NB cells.
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PMID:Heterogeneity of neuroblastoma cell lines in insulin-like growth factor 1 receptor/Akt pathway-mediated cell proliferative responses. 2371 Jul 10