Multiple proteins bind the insulin response element in the human IGFBP-1 promoter

Powell, David R.; Allander, Susanne V.; Scheimann, Ann O.; Wasserman, Richard M.; Durham, Susan K.; Suwanichkul, Adisak

doi:10.1016/0955-2235(95)00034-8

Cited by 26 publications

(18 citation statements)

References 27 publications

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“…The IRSs present in PEPCK, IGFBP-1, and other genes are highly homologous and have been shown to bind FKHR, HNF3, and other related factors (18,29,32,36,37,39) of the Fox(o) subgroup (61) of the forkhead/winged helix family. FKHR regulates insulin inhibition of basal IGFBP-1 activity by binding to the IRSs (38,41).…”

Section: Discussionmentioning

confidence: 99%

“…HNF3, a member of the winged helix transcription factor family (34,35), was shown to bind the IRSs present in the PEPCK and IGFBP-1 promoters as well as in other promoters (18,29,32,36,37), and mutations in the IRSs of the PEPCK or IGFBP-1 genes that reduce HNF3 binding also reduce glucocorticoid-induced transcription (18,21,32). However, transactivation by HNF3 proteins does not appear to be regulated by insulin (38).…”

mentioning

confidence: 99%

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Gene- and Activation-specific Mechanisms for Insulin Inhibition of Basal and Glucocorticoid-induced Insulin-like Growth Factor Binding Protein-1 and Phosphoenolpyruvate Carboxykinase Transcription

Yeagley¹,

Guo²,

Unterman³

et al. 2001

Journal of Biological Chemistry

105

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Gene- and Activation-specific Mechanisms for Insulin Inhibition of Basal and Glucocorticoid-induced Insulin-like Growth Factor Binding Protein-1 and Phosphoenolpyruvate Carboxykinase Transcription

Yeagley¹,

Guo²,

Unterman³

et al. 2001

Journal of Biological Chemistry

105

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“…This model, which is apparently consistent with the convergence of Foxa2 and PGC-1β in mediating hepatic insulin action on hepatic lipid metabolism (58), falls short of reconciling the phenotype of elevated plasma TG levels with the cytosolic localization of Foxa2 in insulin-resistant states (56). There are studies showing that although Foxa2 binds to the promoter of several hepatic genes, including PEPCK, G6Pase, insulin-like growth factor binding protein 1 (IGFBP-1), and tyrosine aminotransferase (TAT), its binding does not confer insulin responsiveness to target gene expression (59)(60)(61)(62)(63). Consistent with these observations, Zhang et al (64) have shown that Foxa2 does not alter its subcellular localization, as Foxa2 remains constitutively nuclear when the liver undergoes a metabolic shift from fed to fasting states.…”

Section: Figure 10mentioning

confidence: 99%

FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice

Kamagaté¹,

Qu²,

Perdomo³

et al. 2008

J. Clin. Invest.

188

241

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Excessive production of triglyceride-rich VLDL is attributable to hypertriglyceridemia. VLDL production is facilitated by microsomal triglyceride transfer protein (MTP) in a rate-limiting step that is regulated by insulin. To characterize the underlying mechanism, we studied hepatic MTP regulation by forkhead box O1 (FoxO1), a transcription factor that plays a key role in hepatic insulin signaling. In HepG2 cells, MTP expression was induced by FoxO1 and inhibited by exposure to insulin. This effect correlated with the ability of FoxO1 to bind and stimulate MTP promoter activity. Deletion or mutation of the FoxO1 target site within the MTP promoter disabled FoxO1 binding and resulted in abolition of insulin-dependent regulation of MTP expression. We generated mice that expressed a constitutively active FoxO1 transgene and found that increased FoxO1 activity was associated with enhanced MTP expression, augmented VLDL production, and elevated plasma triglyceride levels. In contrast, RNAi-mediated silencing of hepatic FoxO1 was associated with reduced MTP and VLDL production in adult mice. Furthermore, we found that hepatic FoxO1 abundance and MTP production were increased in mice with abnormal triglyceride metabolism. These data suggest that FoxO1 mediates insulin regulation of MTP production and that augmented MTP levels may be a causative factor for VLDL overproduction and hypertriglyceridemia in diabetes.

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“…IGFBP1 is expressed in the liver, kidney and decidua (Rajaram et al 1997). The liver is the major source for the circulating IGFBP1 and its synthesis is centrally regulated by insulin that represses IGFBP1 at the transcriptional level (Brismar et al 1994, Powell et al 1995. Other factors, including hypoxia, pro-inflammatory cytokines, cAMP, glucocorticoids and oxidative stress stimulate the synthesis of IGFBP1 (Mesotten et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Carnosine decreases IGFBP1 production in db/db mice through suppression of HIF-1

Forsberg¹,

Botusan²,

Wang³

et al. 2015

Journal of Endocrinology

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IGF binding protein 1 (IGFBP1) is a member of the binding proteins for the IGF with an important role in glucose homeostasis. Circulating IGFBP1 is derived essentially from the liver where it is mainly regulated negatively by insulin. Carnosine, a natural antioxidant, has been shown to improve metabolic control in different animal models of diabetes but its mechanisms of action are still not completely unraveled. We therefore investigate the effect of carnosine treatment on the IGFBP1 regulation in db/db mice. Db/db mice and heterozygous non-diabetic mice received for 4 weeks regular water or water supplemented with carnosine. Igfbp1 mRNA expression in the liver was evaluated using qPCR and the protein levels in plasma by western blot. Plasma IGF1 and insulin were analyzed using immunoassays. HepG2 cells were used to study the in vitro effect of carnosine on IGFBP1. The modulation of hypoxia inducible factor-1 alpha (HIF-1a) which is the central mediator of hypoxia-induction of IGFBP1 was analyzed using: WB, reporter gene assay and qPCR. Carnosine decreased the circulating IGFBP1 levels and the liver expression Igfbp1, through a complex mechanism acting both directly by suppressing the HIF-1a-mediated IGFBP1 induction and indirectly through increasing circulating insulin level followed by a decrease in the blood glucose levels and increased the plasma levels or IGF1. Reduction of IGFBP1 in diabetes through insulin-dependent and insulin-independent pathways is a novel mechanism by which carnosine contributes to the improvement of the metabolic control in diabetes.

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Multiple proteins bind the insulin response element in the human IGFBP-1 promoter

Cited by 26 publications

References 27 publications

Gene- and Activation-specific Mechanisms for Insulin Inhibition of Basal and Glucocorticoid-induced Insulin-like Growth Factor Binding Protein-1 and Phosphoenolpyruvate Carboxykinase Transcription

Gene- and Activation-specific Mechanisms for Insulin Inhibition of Basal and Glucocorticoid-induced Insulin-like Growth Factor Binding Protein-1 and Phosphoenolpyruvate Carboxykinase Transcription

FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice

Carnosine decreases IGFBP1 production in db/db mice through suppression of HIF-1

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