IGF-dependent and IGF-independent actions of IGF-binding protein-1 and -2: implications for metabolic homeostasis

Wheatcroft, Stephen; Kearney, Mark T.

doi:10.1016/j.tem.2009.01.002

Cited by 243 publications

(240 citation statements)

References 105 publications

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“…The reduction in serum IGF-1 could indicate amelioration of an IGF-1 signaling defect in skeletal muscle (10,26). Alternatively, the increase in IGFBP-1 could stimulate IGF-1 action at the cellular level, despite lower serum IGF-1 (27,28). Higher serum IGFBP-1 could reflect improved insulin sensitivity (28), which has been shown with the treatment of acidosis and would reduce muscle proteolysis (29,30).…”

Section: Discussionmentioning

confidence: 98%

“…Alternatively, the increase in IGFBP-1 could stimulate IGF-1 action at the cellular level, despite lower serum IGF-1 (27,28). Higher serum IGFBP-1 could reflect improved insulin sensitivity (28), which has been shown with the treatment of acidosis and would reduce muscle proteolysis (29,30). It should be noted that the decrease in serum IGF-1 in our study contrasts with previous findings of an acidosis-induced impairment of growth hormone (GH)-stimulated IGF-1 expression (31).…”

Section: Discussionmentioning

confidence: 99%

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Effects of Oral Sodium Bicarbonate in Patients with CKD

Abramowitz

Melamed

Bauer³

et al. 2013

Clinical Journal of the American Society of Nephrology

121

106

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SummaryBackground and objectives Metabolic acidosis contributes to muscle breakdown in patients with CKD, but whether its treatment improves functional outcomes is unknown. The choice of dose and tolerability of high doses remain unclear. In CKD patients with mild acidosis, this study evaluated the dose-response relationship of alkali with serum bicarbonate, its side effect profile, and its effect on muscle strength. Conclusions NaHCO 3 supplementation produces a dose-dependent increase in serum bicarbonate and improves lower extremity muscle strength after a short-term intervention in CKD patients with mild acidosis. Long-term studies are needed to determine if this finding translates into improved functional status.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Effects of Oral Sodium Bicarbonate in Patients with CKD

Abramowitz

Melamed

Bauer³

et al. 2013

Clinical Journal of the American Society of Nephrology

121

106

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“…Normal nerve (Figure 1d, upper right panel) and traumatic neuroma (Figure 1d, middle right panel) expressed IGFBP-1 weakly compared with schwannoma. As IGFBP-2 acts via the same integrins as IGFBP-1 (Perks et al, 2007), displaying some similarities in signalling (Wheatcroft and Kearney, 2009), we tested whether Schwann and schwannoma cells release IGFBP-2. We demonstrated that both cell types release IGFBP-2 equally (Figure 1e).…”

Section: Igfbp-1 Is Upregulated and Released Only From Schwannoma Cellsmentioning

confidence: 99%

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates human schwannoma proliferation, adhesion and survival

et al. 2011

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Merlin is a tumour suppressor involved in the development of a variety of tumours including mesotheliomas. Neurofibromatosis type 2 (NF2), a dominantly inherited tumour disease, is also caused by loss of merlin. NF2 patients suffer from multiple genetically well-defined tumours, schwannomas are most frequent among those. Using our in vitro model for human schwannoma, we found that schwannoma cells display enhanced proliferation because of the overexpression/activation of platelet-derived growth factor receptor and ErbB2/3, increased cell-matrix adhesion because of the overexpression of integrins, and decreased apoptosis. Mechanisms underlying schwannomas basal proliferation and cell-matrix adhesion are not understood. Here, we investigated insulin-like growth factor-binding protein-1 (IGFBP-1), which is expressed and released from central nervous system tumours and strongly overexpressed in schwannoma at the mRNA level. IGFBP-1 acts via b1-integrin and focal-adhesion-kinase (FAK), which are strongly overexpressed and basally activated in schwannoma. Using short hairpin RNA knockdown, small inhibitors and recombinant IGFBP-1, we demonstrate that schwannoma cells, in contrast to Schwann cells, release IGFBP-1 that activates the Src/FAK pathway, via integrin b1, potentiating schwannoma's proliferation and cell-matrix adhesion. We show that FAK localizes to the nucleus and Src triggers IGFBP-1 production. Further, we observed downregulation of the tumour-suppressor phosphatase and tensin homolog in schwannoma cells leading to increased activity of antiapoptotic AKT. Thus, IGFBP-1/integrin b1/Src/FAK pathway has a crucial role in merlin-related tumourigenesis and therefore represents an important therapeutic target in the treatment of merlin-deficient tumours.

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“…In this work, evidence is provided for the coupling of pleiotropic functions of IGFBP‐2 being mediated by the RGD‐motif, which is primarily considered to be IGF‐independent (Wheatcroft & Kearney, 2009). However, coupling of reproductive development and lifespan has been clearly demonstrated in Caenorhabditis elegans (Dillin et al ., 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Also, in breast cancer, IGFBP‐2 exerts malignant potential, and again, this depends on the RGD‐motif but involves regulation of estrogen receptors as demonstrated by the Perks laboratory (Foulstone et al ., 2013). In addition, the RGD‐domain has been discussed in a context with metabolic functions of IGFBP‐2 (Wheatcroft & Kearney, 2009). In fact, by direct comparison of D‐ and E‐mice, we were able to demonstrate that the RGD‐motif present in IGFBP‐2 is involved in the regulation of GLUT4 trafficking and glucose clearance after oral glucose administration (Reyer et al ., 2015).…”

Section: Introductionmentioning

confidence: 99%

Dissociation of somatic growth, time of sexual maturity, and life expectancy by overexpression of an RGD ‐deficient IGFBP ‐2 variant in female transgenic mice

et al. 2015

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SummaryImpaired growth is often associated with an extension of lifespan. However, the negative correlation between somatic growth and life expectancy is only true within, but not between, species. This can be observed because smaller species have, as a rule, a shorter lifespan than larger species. In insects and worms, reduced reproductive development and increased fat storage are associated with prolonged lifespan. However, in mammals the relationship between the dynamics of reproductive development, fat metabolism, growth rate, and lifespan are less clear. To address this point, female transgenic mice that were overexpressing similar levels of either intact (D‐mice) or mutant insulin‐like growth factor‐binding protein‐2 (IGFBP‐2) lacking the Arg‐Gly‐Asp (RGD) motif (E‐ mice) were investigated. Both lines of transgenic mice exhibited a similar degree of growth impairment (−9% and −10%) in comparison with wild‐type controls (C‐mice). While in D‐mice, sexual maturation was found to be delayed and life expectancy was significantly increased in comparison with C‐mice, these parameters were unaltered in E‐mice in spite of their reduced growth rate. These observations indicate that the RGD‐domain has a major influence on the pleiotropic effects of IGFBP‐2 and suggest that somatic growth and time of sexual maturity or somatic growth and life expectancy are less closely related than thought previously.

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IGF-dependent and IGF-independent actions of IGF-binding protein-1 and -2: implications for metabolic homeostasis

Cited by 243 publications

References 105 publications

Effects of Oral Sodium Bicarbonate in Patients with CKD

Effects of Oral Sodium Bicarbonate in Patients with CKD

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates human schwannoma proliferation, adhesion and survival

Dissociation of somatic growth, time of sexual maturity, and life expectancy by overexpression of an RGD ‐deficient IGFBP ‐2 variant in female transgenic mice

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