By regulating the production of IGFBPs or the removal of IGFBPs. Among the ten current known IGFBPs, at least six of them bind IGFs with high affinity. While the full range of functional roles of the binding proteins remains to be clarified, some of their actions are known. First, IGFBPs can function as IGF carriers, protecting the IGFs from degradation while they are being transported through tissues. It is well known that binding proteins can also act as stores of IGFs within the tissue, which helps to smooth any fluctuations in IGF production or transport over time. It has been demonstrated theoretically, using a reactivediffusion transport model, that reversible binding between IGFs and diffusible IGFBPs can significantly increase the uptake rate of free IGF into a tissue). Most importantly, targeted degradation of IGF binding proteins can lead to substantial increases in the free IGF concentration in the tissue, compared to the concentration in the plasma, with the rate of degradation of the binding proteins controlling the free IGF concentration in the tissue. That is, tissue can potentially tune their exposure to IGF by modifying the rate of degradation of the IGF binding partner. Different IGFBP proteases may selectively target IGFBPs for degradation, potentially giving fine control over the total IGF concentration in the tissue and the ratio of IGF-I/IGF-II. For example, serine protease is reported to be mainly responsible for cleavage of IGFBP5, whilst metalloproteinase ADAM 12-S primarily degrades IGFBP3 and IGFBP5 but not IGFBP1, 22, 24 and 26. In addition, matrix metalloproteinases are capable of increasing bioavailability of IGF-I by degrading IGFBP 1, 23, and 25. IGFBP6 is an O-linked glycoprotein. It is known that O-glycosylation inhibits human IGFBP6 degradation by chymotryspin and tryspin. In addition, Oglycosylation also helps maintain IGFBP6 in soluble form by inhibiting its binding to glycosaminoglycans and cell membranes. These targeted mechanisms provide tissue with the means to adjust their free IGF concentration. That is, cells in tissues can ‘tune’their IGF exposure, effectively independently to the plasma concentration, to suit the tissue’s particular needs. It is Cinoxacin expected that these tuning processes would contribute to the maintenance of tissue homeostasis. IGFBPs are also capable of blocking IGFs access to IGF receptors through sequestration. IGFs have a 2�C50 fold greater affinity for IGFBPs than that of the IGF-IR receptor itself. It has been theoretically demonstrated that extracellular matrix fixed IGFBPs within the tissue have no influence on the steady-state free IGF-I and �CII concentrations in the tissue if the half-lives of these ECM fixed IGFBPs are prolonged by ECM proteins. IGF-independent cellular actions of the IGFBPs have also been reported. Among six IGFBPs, IGFBP1-5 have approximately similar affinities for IGF-I and �CII, but IGFBP6 has a 20�C 100 fold higher affinity for IGF-II than for IGF-I. Because of the similar affinities, as a good Pimozide approximation for many purposes, one may simply sum the concentrations of IGFBP1�C5, and treat this as one functional group of BPs, and treat IGFBP6 as a second functional group. In our previous study, we have theoretically demonstrated that Bhakt et al’s experimental results for equilibrium competitive binding can be successfully reproduced using a reversible Langmuir sorption isotherm involving these two ‘functional groupings’of IGFBPs. The effect of this competitive binding on ligand and complex formation will be included in this study. A third possible mechanism to regulate the IGF-IR receptor complex concentration in the tissue is to regulate the IGF-IR receptor density.