THE GENERATION OF INOSITOLGLYCAN MEDIATORS FROM RAT-LIVER PLASMA-MEMBRANES - THE ROLE OF GUANINE-NUCLEOTIDE BINDING-PROTEINS

The guanine nucleotide dependence for the generation of inositolglycan second messengers from rat liver plasma membranes has been investigated. Plasma membranes, when treated with insulin release a soluble mediator substance which activates pyruvate dehydrogenase (PDH). Guanosine 5′-[3-thio]triphosphate (GTPγS) was found to be as potent as insulin in stimulating mediator release. The stimulatory effects of GTPγS required the presence of magnesium and following preincubation of membranes with guanosine 5′-[2-thio]diphosphate (GDPβS) the stimulation of mediator release by either insulin or GTPγS was blocked. The activation of PDH by mediator fractions produced in response to either insulin or GTPγS was abolished following treatment of the fractions with anti-inositolglycan antibodies. The significance of these observations with respect to the possible involvement of a regulatory guanine-nucleotide binding protein (G-protein) in the generation of insulin mediators is discussed. © 1992.