TY - JOUR
T1 - Modulatory effects of peroxovanadates on insulin receptor binding
AU - KWONG, Daniel W J
AU - Leung, W. N.
AU - Xu, Minghua
AU - Zhu, Shang Quan
AU - Cheng, Christopher H.K.
N1 - Funding Information:
The authors wish to thank Prof Sunney I. Chan of Caltech for valuable suggestions and a critical review of the manuscript. This work was supported by a Faculty Research Grant (FRG /92-93 / R-50) from Hong Kong Baptist University SQZ was a Resident Fellow of United College, The Chinese University of Hong Kong.
PY - 1996/11/15
Y1 - 1996/11/15
N2 - The insulin-mimetic effects exhibited by vanadate, hydrogen peroxide, and some peroxovanadates have recently been shown to occur, at least in part, through an activation of the insulin receptor tyrosine kinase activity. In this study, we examine the effects of these compounds on insulin receptor binding using receptor preparations from human placental membranes. Among the 16 vanadium(V)-peroxo complexes studied, the [VO(O2)2(bipy)]- ion, where bipy = 2,2'-bipyridine, was found to increase insulin receptor binding by 24%, whereas the [VO(O2)2(en)]- ion, where en = ethylenediamine, was found to reduce insulin receptor binding by about the same amount under steady- state conditions. Scatchard analysis of the binding data indicates that the observed effect of the [VO(O2)2(bipy)]- ion on insulin receptor binding is exerted mainly at the high-capacity low-affinity sites. Furthermore, this modulatory effect is reversible and requires a continuous presence of the compound. By perturbing the membrane environment of the insulin receptor, we have shown that an intact membrane structure is essential for an observable effect. The observed modulation of insulin receptor binding by peroxovanadates is interpreted in terms of a ternary complex model in which the peroxovanadate acts as an allosteric effector modulating the binding equilibrium between insulin and its receptor.
AB - The insulin-mimetic effects exhibited by vanadate, hydrogen peroxide, and some peroxovanadates have recently been shown to occur, at least in part, through an activation of the insulin receptor tyrosine kinase activity. In this study, we examine the effects of these compounds on insulin receptor binding using receptor preparations from human placental membranes. Among the 16 vanadium(V)-peroxo complexes studied, the [VO(O2)2(bipy)]- ion, where bipy = 2,2'-bipyridine, was found to increase insulin receptor binding by 24%, whereas the [VO(O2)2(en)]- ion, where en = ethylenediamine, was found to reduce insulin receptor binding by about the same amount under steady- state conditions. Scatchard analysis of the binding data indicates that the observed effect of the [VO(O2)2(bipy)]- ion on insulin receptor binding is exerted mainly at the high-capacity low-affinity sites. Furthermore, this modulatory effect is reversible and requires a continuous presence of the compound. By perturbing the membrane environment of the insulin receptor, we have shown that an intact membrane structure is essential for an observable effect. The observed modulation of insulin receptor binding by peroxovanadates is interpreted in terms of a ternary complex model in which the peroxovanadate acts as an allosteric effector modulating the binding equilibrium between insulin and its receptor.
UR - http://www.scopus.com/inward/record.url?scp=0030589178&partnerID=8YFLogxK
U2 - 10.1016/0162-0134(96)00038-4
DO - 10.1016/0162-0134(96)00038-4
M3 - Journal article
C2 - 8893518
AN - SCOPUS:0030589178
SN - 0162-0134
VL - 64
SP - 163
EP - 180
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
IS - 3
ER -