Monoclonal antibodies for the human insulin receptor

1985 ◽  
Vol 13 (1) ◽  
pp. 95-96
Author(s):  
MARIA SOOS ◽  
MICHAEL D. BARON ◽  
KENNETH SIDDLE
Keyword(s):  
Monoclonal Antibodies ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Human Insulin Receptor

scholarly journals Monoclonal antibodies reacting with multiple epitopes on the human insulin receptor

1986 ◽  
Vol 235 (1) ◽  
pp. 199-208 ◽  
Author(s):  
M A Soos ◽  
K Siddle ◽  
M D Baron ◽  
J M Heward ◽  
J P Luzio ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Human Placenta ◽  
Structure And Function ◽  
Beta Subunits ◽  
Intact Cells ◽  
Receptor Structure ◽  
Human Insulin Receptor ◽  
And Function

Monoclonal antibodies for the human insulin receptor were produced following immunization of mice with IM-9 lymphocytes and/or purified placental receptor. Four separate fusions yielded 28 antibodies, all of which reacted with receptor from human placenta, liver and IM-9 cells. Some antibodies cross-reacted to varying degrees with receptor from rabbit, cow, pig and sheep, but none reacted with rat receptor. At least 10 distinct epitopes were recognized as indicated by species specificity and binding competition experiments. All of these epitopes appeared to be on extracellular domains of the receptor as shown by binding of antibodies to intact cells. In some cases the epitopes were further localized to alpha or beta subunits by immunoblotting. Several antibodies inhibited binding of 125I-insulin to the receptor, some had no effect on binding, and others enhanced the binding of 125I-insulin. It is concluded that these antibodies will be valuable probes of receptor structure and function.

scholarly journals Insulin-like and insulin-inhibitory effects of monoclonal antibodies for different epitopes on the human insulin receptor

1987 ◽  
Vol 242 (1) ◽  
pp. 123-129 ◽  
Author(s):  
R Taylor ◽  
M A Soos ◽  
A Wells ◽  
M Argyraki ◽  
K Siddle
Keyword(s):  
Monoclonal Antibodies ◽  
Insulin Receptor ◽  
Human Insulin ◽  
Insulin Binding ◽  
Metabolic Effects ◽  
Alpha Subunit ◽  
Inhibitory Effects ◽  
Molar Basis ◽  
Human Insulin Receptor ◽  
Receptor Beta

Monoclonal antibodies previously shown to react with five distinct epitopes on the human insulin receptor were tested for their metabolic effects on isolated human adipocytes. Two antibodies which reacted with receptor alpha-subunit and completely inhibited 125I-insulin binding mimicked the actions of insulin to stimulate lipogenesis from [14C]glucose and to inhibit catecholamine-induced lipolysis. On a molar basis, these antibodies were comparable in potency with insulin itself. Two other antibodies which decreased insulin binding only slightly or not at all also mimicked these metabolic effects of insulin. One of these antibodies reacted with receptor beta-subunit. In contrast, a further antibody which reacted with alpha-subunit and inhibited insulin binding did not affect basal lipogenesis or catecholamine-induced lipolysis, but was able to antagonize the effects of insulin on these processes. The same antibody antagonized the insulin-like effect of another antibody with which it competed in binding to insulin receptor, but not the effect of an antibody which bound independently to the receptor. It is concluded that binding of ligand at or close to the insulin-binding site is neither necessary nor sufficient to trigger insulin-like metabolic effects, which may rather depend on some general property of antibodies, such as their ability to cross-link and aggregate receptor molecules.

Sign in / Sign up

Export Citation Format

Share Document