Insulin action is mimicked by polyclonal antireceptor antibodies that activate the insulin receptor tyrosine kinase.
The insulin-like properties of anti-insulin receptor antibodies (P95 Ab) that have been characterized as being directed against the receptor beta-subunit, were studied as probes to assess the interrelationship between insulin action and receptor phosphorylation. When tested on intact cells, P95 Ab mimicked insulin effects. On isolated fat cells, they stimulated 2-deoxyglucose (2-DG) transport and lipogenesis and the P95 antibody maximal effects (173 and 232% of the control values, respectively) represented about 50% of the maximal effects elicited by insulin (317 and 475% of the control values). On cultured Zajdela hepatoma cells (ZHC cells), P95 Ab also mimicked insulin action on the incorporation of [U-14C]glucose into glycogen (158 and 207% of the control value for antibody- and insulin-treated cells, respectively). In all cases the antibody effects were dose-dependent, specific and, when maximal, were not additive with those elicited by insulin. When tested in a cell-free system, P95 Ab faithfully reproduced insulin action on the phosphorylation of the receptor beta-subunit. The maximal antibody and insulin effects (317 and 328% of the control value, respectively) were not additive. P95 Ab were also equally potent as insulin to stimulate the receptor-mediated phosphorylation of an exogenous substrate (365 and 379% of the control value in P95 antibody- and insulin-treated receptors, respectively). As well, P95 Ab proved as able as insulin in stimulating the tyrosine kinase activity of the receptor (89% of the hormone effect) when the activation was carried out in vivo. Taken together, these results are consistent with a role for the kinase activity of the insulin receptor in mediating the action of insulin.
Caron
M
M
Laboratoire de Biochimie, INSERM U181, Faculté de Médecine Saint-Antoine, Paris, France.
Cherqui
G
G
Melin
B
B
Wicek
D
D
Capeau
J
J
Picard
J
J
D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000502:physiology*; D002478:Cells, Cultured / Q000378:metabolism; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000502:physiology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin; D013552:Swine
D000906:Antibodies; D007328:Insulin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D005947:Glucose