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KMID : 0613820070170091224
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Journal of Life Science
2007 Volume.17 No. 9 p.1224 ~ p.1231
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Effects of Glucose on Insulin-like Growth Factor Binding-5 Expression in Human Fibroblasts
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Ryu Hye-Young
Hwang Hye-Jung
Kim In-Hye
Ryu Hong-Soo
Nam Tak-Jeong
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Abstract
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Insulin-like growth factor-I (IGF-I) and IGF-Ⅱ have structure like insulin. In contrast to insulin, however, the bioavaility of IGFs is modulated by the IGF-binding protein (IGFBPs). Each of IGFBPs was different with molecular masses, biological characteristics, and immunological properties.. Human fibroblasts secrete IGFBPs that can modify IGF-I action. In diabetes mellitus, the most study of IGF systems have been investigated in insulin-dependent diabetes mellitus, non-insulin-dependent diabetes mellitus, and streptozotocin-induced animals in vivo. Recently, a little research regarding the IGFs system has been proposed in portion of cell in vitro. In this study, effects of low or high glucose condition on IGFBP-5 in GM10 was investigated. By western blotting analysis, IGFBP-5 level decreased in cells cultured at high glucose, but IGFBP-5 level of mRNA didn't change. IGFBP-5 protease that cleaves IGFBP-5 in conditioned medium had was inhibited by EDTA and heparin, like serine protease and metalloprotease. Furthermore, the protease activity was increased in high glucose cultivated condition. In results of gelatin zymography, molecular weight of proteolytic metalloenzymes was indentified 69-kDa and protease activity was increased in time-dependent manner. Although the mechanism has yet to be determined, IGFBP-5 proteolysis in GM10 cells cultured with high glucose may increase effects of IGFs to decrease the glucose level through dissociation of IGFs from IGFBPs. Therefore, we suggest that IGF-Ⅰ and IGFBPs could be potential models in study of pathophysiology such as diabetes mellitus.
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KEYWORD
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IGF-Ⅰ, IGFBP-5, glucose, diabetes
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