Glycosaminoglycans increase levels of free and bioactive IGF-I in vitro
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Glycosaminoglycans increase levels of free and bioactive IGF-I in vitro. / Møller, Anne Vestergård; Jørgensen, Søren Peter; Chen, Jian Wen; Larnkjær, Anni; Ledet, Thomas; Flyvbjerg, Allan; Frystyk, Jan.
In: European Journal of Endocrinology, Vol. 155, No. 2, 2006, p. 297-305.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Glycosaminoglycans increase levels of free and bioactive IGF-I in vitro
AU - Møller, Anne Vestergård
AU - Jørgensen, Søren Peter
AU - Chen, Jian Wen
AU - Larnkjær, Anni
AU - Ledet, Thomas
AU - Flyvbjerg, Allan
AU - Frystyk, Jan
PY - 2006
Y1 - 2006
N2 - Background: It is unclear how IGFs become separated from their IGF-binding proteins (IGFBPs) in vivo. However, the IGFBPs possess binding sites for glycosaminoglycans (GAGs) and interaction with GAGs alters IGFBP ligand affinity. Accordingly, GAGs may control IGF bioavailability. To test this hypothesis, we investigated the effect of GAGs on serum levels of free and bioactive IGF-I, total IGF-I, and IGFBPs in vitro. Methods: Serum was incubated with increasing concentrations of six different GAGs (heparin, tinzaparin (Innohep®), dermatan sulfate, heparan sulfate, non-anticoagulant (nac) heparin, and nac low-molecular weight heparin). To investigate for reversibility, heparin was co-incubated with protamine sulfate (PS). Finally, the effect of heparin was studied in serum from pregnant and post partum women, normal subjects and patients with type 1 diabetes. Results: All GAGs increased free IGF-I in a dose-dependent manner (P < 0.0001), whereas total IGF-I and IGFBP levels remained unchanged. However, the potency of the GAGs differed significantly (P < 0.0001) and did not relate to their anti-coagulating activity. The effect of heparin on free IGF-I was fully reversed by PS. Heparin increased free and bioactive IGF-I in all tested sera (P < 0.0001), but the increase was most pronounced in samples from pregnant women (P < 0.0001). Conclusion: All tested GAGs stimulated the release of free and bioactive IGF-I in several types of serum, most likely by reversible interaction with the IGFBPs. The effect was most pronounced in pregnancy sera, which are characterized by extensive IGFBP-3 proteolysis. Our findings support the view that GAGs localized in the vessel wall and attached to the extracellular matrix control IGF-I tissue accessibility and bioactivity
AB - Background: It is unclear how IGFs become separated from their IGF-binding proteins (IGFBPs) in vivo. However, the IGFBPs possess binding sites for glycosaminoglycans (GAGs) and interaction with GAGs alters IGFBP ligand affinity. Accordingly, GAGs may control IGF bioavailability. To test this hypothesis, we investigated the effect of GAGs on serum levels of free and bioactive IGF-I, total IGF-I, and IGFBPs in vitro. Methods: Serum was incubated with increasing concentrations of six different GAGs (heparin, tinzaparin (Innohep®), dermatan sulfate, heparan sulfate, non-anticoagulant (nac) heparin, and nac low-molecular weight heparin). To investigate for reversibility, heparin was co-incubated with protamine sulfate (PS). Finally, the effect of heparin was studied in serum from pregnant and post partum women, normal subjects and patients with type 1 diabetes. Results: All GAGs increased free IGF-I in a dose-dependent manner (P < 0.0001), whereas total IGF-I and IGFBP levels remained unchanged. However, the potency of the GAGs differed significantly (P < 0.0001) and did not relate to their anti-coagulating activity. The effect of heparin on free IGF-I was fully reversed by PS. Heparin increased free and bioactive IGF-I in all tested sera (P < 0.0001), but the increase was most pronounced in samples from pregnant women (P < 0.0001). Conclusion: All tested GAGs stimulated the release of free and bioactive IGF-I in several types of serum, most likely by reversible interaction with the IGFBPs. The effect was most pronounced in pregnancy sera, which are characterized by extensive IGFBP-3 proteolysis. Our findings support the view that GAGs localized in the vessel wall and attached to the extracellular matrix control IGF-I tissue accessibility and bioactivity
UR - http://www.scopus.com/inward/record.url?scp=33747734653&partnerID=8YFLogxK
U2 - 10.1530/eje.1.02203
DO - 10.1530/eje.1.02203
M3 - Journal article
C2 - 16868144
AN - SCOPUS:33747734653
VL - 155
SP - 297
EP - 305
JO - Acta Endocrinologica, Supplement
JF - Acta Endocrinologica, Supplement
SN - 0804-4635
IS - 2
ER -
ID: 249251955