Insulin-receptor antibodies mimic a late insulin effect

Abstract

AUTOANTIBODIES against the insulin receptor are found in patients with a rare form of extreme insulin resistance associated with acanthosis nigricans¹. These antibodies are primarily polyclonal IgGs, compete with insulin for binding to its receptor^2,3, immunoprecipitate solubilised insulin receptors⁴, and have been used as probes of insulin action. The acute action of the antibodies is to mimic many of insulin's biological effects, particularly those which occur rapidly after hormone binding to its cell-surface receptors^5–9. In addition, insulin exerts biological effects which appear more slowly. For example, insulin treatment of 3T3-L1 fatty fibroblasts increases the activity of lipo-protein lipase maximally after 2–4 d but is without effect during the first 4 h (refs 10, 11). Some investigators have suggested that these slower effects may be mediated by different mechanisms from those involved in the production of the acute effects^12,13. We now report that autoantibodies against the insulin receptor mimic this long-term insulin effect on lipoprotein lipase.