Insulin-like Growth Factor Binding Protein-2 (IGFBP-2) is a Marker for the Metabolic Syndrome

Heald, Adrian; Kaushal, Kalpana; Siddals, Kirk; Rudenski, A; Anderson, Simon; Gibson, John M.

doi:10.1055/s-2006-924320

Cited by 117 publications

(109 citation statements)

References 22 publications

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“…When we silenced FASN in the PCa cells, however, we found no reduction in the protective effect conferred by hyperglycaemia (in contrast to the amelioration of the effect that we observed with the breast cancer cells; data not shown). The IGF axis is strongly associated with PCa, and IGFBP2 is an established mitogen and survival factor for PCa (Chatterjee et al 2004, Uzoh et al 2011 and has been reported to be associated with metabolic status (Heald et al 2006). IGFBP2 can act in both: an IGF-IR-dependent manner in PC3 cells and intrinsically (independent of IGF interaction) in DU145 cells (Uzoh et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Hyperglycaemia-induced chemoresistance of prostate cancer cells due to IGFBP2

Biernacka¹,

Uzoh²,

Zeng³

et al. 2013

Endocrine-Related Cancer

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Clinically relevant prostate cancer (PCa) is more frequent in Westernised societies and increasingly men have co-morbidities associated with a Western lifestyle, primarily diabetes, characterised by hyperinsulinaemia and hyperglycaemia. IGFs and their binding proteins (IGFBPs) are important mediators of the effects of nutrition on growth and play a key role in the development of PCa. We used DU145, PC3 and LNCaP PCa cell lines to examine how hyperglycaemia altered their response to docetaxel. Trypan Blue dye-exclusion assay was used to determine the percentage of cell death. Protein abundance was determined using western immunoblotting. Levels of IGFBP2 were measured using an ELISA. IGFBP2 gene silencing was achieved using siRNA technology. DNA methylation was assessed using combined bisulphide restriction analysis. Acetylation status of histones H3 and H4 associated with IGFBP2 gene was assessed using chromatin immunoprecipitation assay. Hyperglycaemia reduced docetaxel-induced apoptosis by 40% for DU145 cells and by 88% for LNCaP cells. This reduced cell death was mediated by a glucose-induced up-regulation of IGFBP2, as silencing IGFBP2 negated the survival effect of high glucose. Glucose increased IGFBP2 via increasing the acetylation of histones associated with the IGFBP2 gene promoter. This finding could have important implications in relation to therapeutic strategies as epigenetic modulation could be reversible.

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Section: Discussionmentioning

confidence: 99%

Hyperglycaemia-induced chemoresistance of prostate cancer cells due to IGFBP2

Biernacka¹,

Uzoh²,

Zeng³

et al. 2013

Endocrine-Related Cancer

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“…These include parameters of obesity and products released by adipose tissue, plasma insulin levels and insulin-like growth factors, liver enzymes, C-reactive protein and circulating metabolites, several components of circulating lipoproteins, microalbuminuria, and markers of increased cellular inflammation. [51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] The status of these biomarkers as causative factors, either in generation of the metabolic syndrome or directly in atherogenesis, at present is uncertain. Some of them have been implicated as causes, but others as a reflection of a metabolic abnormality.…”

mentioning

confidence: 99%

Gamma-Glutamyl Transferase

Grundy

2007

ATVB

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“…25) Heald et al showed that a lower concentration of IGFBP2 in serum is a marker for elevating serum fasting glucose in patients with type 2 diabetes. 24) Therefore, these results suggest that lower IGFBP2 in serum might be influenced by lower IGFBP2 gene expression in the liver.…”

Section: Discussionmentioning

confidence: 82%

“…22,23) In particular, Nr4a3 and Adrb3 genes were involved in responses to stimulus (GO:50896), and Adiponectin genes were involved in lipid metabolism (GO:6629). Cluster 3 included the IGFBP2 gene, 24,25) however, there were no statistically overrepresented genes (more than 10 genes) within a specific GO term (pϽ0.01). Cluster 4 included the Pla2g7 26) gene, which was not assigned a GO term.…”

Section: Microarray Analysis Of Gene Expression Profiles In Diabetes-mentioning

confidence: 95%

DNA Microarray Analysis of Whole Blood Cells and Insulin-Sensitive Tissues Reveals the Usefulness of Blood RNA Profiling as a Source of Markers for Predicting Type 2 Diabetes

Hayashi

Kajimoto

Iida

et al. 2010

Biological & Pharmaceutical Bulletin

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To determine if gene expression profiling of whole blood cells is a useful source of markers for the early diagnosis of the onset of type 2 diabetes, we examined gene expression profiling of whole blood cells and type 2 diabetes-related organs, such as liver, adipose tissue, and skeletal muscle, of Otsuka Long-Evans Tokushima Fatty (OLETF) rats. At the age of 6 weeks, RNA was isolated from tissues of fasted OLETF and control LongEvans Tokushima Otsuka (LETO) rats. Gene expression was analyzed using the Agilent rat oligo microarray. Gene ontology analysis showed that gene expression of biologically meaningful groups of genes in liver, adipose tissue, and skeletal muscle, which are involved in the pathogenesis of type 2 diabetes, differed between OLETF and LETO rats. Three hundred genes of whole blood cells were differentially expressed. Four out of these 300 genes were related to the insulin-signaling pathway and 57 out of 300 genes were up-or down-regulated in at least one tissues in OLETF rats. These results support our hypothesis that gene expression profiling of whole blood cells might be a useful source of markers to predict the onset of type 2 diabetes.

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Insulin-like Growth Factor Binding Protein-2 (IGFBP-2) is a Marker for the Metabolic Syndrome

Cited by 117 publications

References 22 publications

Hyperglycaemia-induced chemoresistance of prostate cancer cells due to IGFBP2

Hyperglycaemia-induced chemoresistance of prostate cancer cells due to IGFBP2

Gamma-Glutamyl Transferase

DNA Microarray Analysis of Whole Blood Cells and Insulin-Sensitive Tissues Reveals the Usefulness of Blood RNA Profiling as a Source of Markers for Predicting Type 2 Diabetes

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