title: Insulin-ricin B hybrid molecules mediate an insulin-associated effect on cells which do not bind insulin.
abstract: A hybrid molecule was constructed by covalently linking, by a disulfide bridge, the hormone insulin to the binding subunit B of the plant toxin ricin (specificity: Gal, GalNAc). Monolayer-cultured MDCK cells, which lack detectable levels of specific plasma membrane 125I-insulin binding but which readily bind 125I-insulin-ricin B, were used in these studies. Binding of insulin-ricin B to these cells could be displaced by lactose and ricin B, but not by insulin. The biological activity of the hybrid, as measured by [14C]glucose incorporation into glycogen, was stimulated in a dose-dependent manner by the hybrid (10(-11)-10(-8) M), whereas glycogen production was not stimulated by insulin alone. The stimulated glycogen labeling in response to the hybrid was also inhibited by lactose and ricin B. When ricin B alone was tested over the same range of concentrations, stimulation of glycogen synthesis was not observed, nor was there any evidence for stimulation when insulin and ricin B were added simultaneously. These data suggested that alternate cell surface receptors (i.e. ricin B receptors) may substitute for specific receptors (i.e. insulin receptors) to convey intracellular metabolic control signals in this cell line.
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D006003:Glycogen / Q000096:biosynthesis; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D007668:Kidney; D055503:Protein Multimerization; D011972:Receptor, Insulin / Q000378:metabolism*; D012276:Ricin / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007328:Insulin; C008147:insulin, iodo-; D006003:Glycogen; D012276:Ricin; D011972:Receptor, Insulin