BIOLOGICAL-ACTIVITY OF IMMUNOREACTIVE INSULIN-LIKE ACTIVITY EXTRACTEDFROM RAT SUBMANDIBULAR-GLAND

Earlier studies indicate the presence of an insulin-like immunoreactiv ity (ILI) in rat submandibular salivary glands (STZ). Previous observa tions also showed that streptozotocin (STZ)-induced diabetes was accom panied by an increase in SSG ILI concentrations. In the present work w e studied the effect of SSG ILI from normal and STZ diabetic rats (ILI -N and ILI-D, respectively) on insulin receptor binding and function i n LMH cell line. ILI-N and ILI-D inhibited I-125-insulin binding to in tact cells and wheat germ agglutinin (WGA)-purified insulin receptors with a high affinity. Furthermore, ILI-N and ILI-D activated, although weakly, the beta-subunit autophosphorylation of solubilized and WGA-p urified insulin receptors. An ATP hydrolytic activity was present in I LI-N and, to a greater extent, in ILI-D extracts, which can at least i n part explain their low potency for activating autophosphorylation an d kinase activity of insulin receptors in vitro. However, after ILI tr eatment of intact cells and immunoprecipitation of insulin receptors, ILI induced a dose-dependent tyrosine phosphorylation of the insulin r eceptor beta-subunit. Finally,; ILI-N and ILI-D stimulated amino acid uptake and lipogenesis in LMH cells. These findings suggest that SSG I LI is biologically active and can participate in metabolic regulations .