Covalent linking of photoreactive insulin to adipocytes produces a prolonged signal

Abstract

The first step of insulin's many cellular functions is specific binding to receptors on the plasma membrane of target cells. The subsequent molecular basis of insulin action, particularly the coupling mechanism(s) involved in transmitting the biological message, remains largely unknown. Our approach to the problem centres on the application of a series of well characterized photo-insulins carrying an aryl-azido or nitro-aryl-azido group in positions A1, B1, B2 or B29 (refs 2--4). Specific binding to membrane components could be demonstrated with B1-, B29- (ref. 5) and A1-photo-insulins as well as a B2-derivative. We now report that lipogenesis is increased to, and maintained at, near-maximal levels for several hours after photoinduced covalent binding of B2- (2-nitro,4-azidophenylacetyl)-des-PheB1-insulin (Napa-DP-insulin) to living adipocytes.