2014
DOI: 10.1038/srep04388
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Cyclic glycine-proline regulates IGF-1 homeostasis by altering the binding of IGFBP-3 to IGF-1

Abstract: The homeostasis of insulin-like growth factor-1 (IGF-1) is essential for metabolism, development and survival. Insufficient IGF-1 is associated with poor recovery from wounds whereas excessive IGF-1 contributes to growth of tumours. We have shown that cyclic glycine-proline (cGP), a metabolite of IGF-1, can normalise IGF-1 function by showing its efficacy in improving the recovery from ischemic brain injury in rats and inhibiting the growth of lymphomic tumours in mice. Further investigation in cell culture su… Show more

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Cited by 45 publications
(74 citation statements)
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“…MFG: middle frontal gyrus; Scale bars: 50 µm and 20 µm vascular remodelling through promoting vasogenesis and angiogenesis [3]. Other than PDGF receptors pericytes also express receptors for other growth factors such as VEGF receptors, transforming growth factor-β (TGF-β) receptors [21] and IGF-1 receptors [22,23]. Apart from the quantitative analysis the images of PD cases ( Figures 1B and 1D) also suggested the Vascular degeneration by showing the morphology of shortened capillaries with indistinct and palely stained pericytes.…”
Section: Discussionmentioning
confidence: 99%
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“…MFG: middle frontal gyrus; Scale bars: 50 µm and 20 µm vascular remodelling through promoting vasogenesis and angiogenesis [3]. Other than PDGF receptors pericytes also express receptors for other growth factors such as VEGF receptors, transforming growth factor-β (TGF-β) receptors [21] and IGF-1 receptors [22,23]. Apart from the quantitative analysis the images of PD cases ( Figures 1B and 1D) also suggested the Vascular degeneration by showing the morphology of shortened capillaries with indistinct and palely stained pericytes.…”
Section: Discussionmentioning
confidence: 99%
“…Interestingly, the activation of IGF-1R was in close correlation with cell proliferation in capillaries, in which these proliferating cells were highly associated with the pericytes (Figure 4). It is known that IGF-1Rs are present in both endothelial cells [33] and pericytes [22,23]. Activation of IGF-1R in the capillaries protects capillaries from ischemic brain injury [22].…”
Section: Discussionmentioning
confidence: 99%
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“…It has been shown that this small peptide acts, as does GPE, by modulating the amount of free IGF-I, the biologically active fraction, by regulating the binding of IGF-I to its binding proteins, particularly to IGFBP3; therefore, it normalizes the function of IGF-I in pathological conditions [86,87]. In this sense, it has been shown that cGP increases the availability of free IGF-I when it is low (as occurs in the brain of RTT patients), but inhibits it when free IGF-I is in high values; this may explain why IGF-I can show such different effects as improving the recovery of brain lesions in rats and decreasing or inhibiting the growth of some tumors in mice [87], but also why cGP improves memory in adult rats [88].…”
Section: Discussionmentioning
confidence: 99%
“…The potential role for IGF-1 in this vascular protection was then evaluated by assessing the expression of both inactivated and phosphorylated IGF-1 receptors in the capillaries after cGP treatment [76]. The IGF-1 receptors appeared to be localized on the pericytes, the capillary cells involved in angiogenesis.…”
Section: Vascular Protection Of Cgp Was Mediated Via Activation Of Igmentioning
confidence: 99%