Effects of covalently linked insulin dimers on receptor kinase activity and receptor down regulation.
Certain covalently linked insulin dimers have previously been found to have a greater ability to bind to the insulin receptor than to stimulate lipogenesis in adipocytes. The present report presents data indicating that the same insulin dimers also have a greater ability to bind to the receptor than to stimulate the kinase activity of the insulin receptor. In particular, one such covalently linked insulin dimer had less than 1% the potency of native insulin in stimulating the receptor kinase although it could bind to the solubilized receptor with 30% the potency of native insulin. In contrast, this dimer could down regulate the insulin receptor with approximately 30% the potency of native insulin. These results suggest that stimulation of the receptor kinase may require more than simple occupancy of the receptor binding site whereas down regulation of the receptor may require only the binding of ligand to the receptor.
D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D046911:Macromolecular Substances; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D010920:Placenta / Q000032:analysis; D011247:Pregnancy; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*
D007328:Insulin; D046911:Macromolecular Substances; D010770:Phosphotransferases; D011972:Receptor, Insulin