Insulin induces tyrosine phosphorylation of the insulin receptor and SHC, and SHC/GRB2 association in cerebellum but not in forebrain cortex of rats

A growth-related branch of the insulin-signaling pathway was studied in the forebrain cortex and cerebellum of Wistar rats. Anesthetized rats received a bolus injection of saline or insulin through the cava vein after which f ragments of cerebellum and forebrain cortex were excised and immediately ho mogenized. Insulin receptor and p46(SHCA) phosphorylation, and p46(SHCA)/GR B2 association were detected by immunoprecipitation and blotting with speci fic antibodies. Insulin stimulated the rapid phosphorylation of its recepto r in cerebellum, followed by p46(SHCA) phosphorylation and GRB2 recruitment . The optimal insulin dose for the induction of p46(SHCA)/GRB2 binding was 60 mu g, and time-course experiments showed that maximum phosphorylation/bi nding occurred 2-3 min after stimulation. Although insulin receptors and SH C were present in forebrain cortex, there was no increase in their phosphor ylation, nor was there any recruitment of GRB2 following stimulation with i nsulin. Thus, although elements involved in the early intracellular respons e to insulin are present in the central nervous system, differences in thei r activation/regulation may account for the functional roles of insulin in these tissues. (C) 1999 Published by Elsevier Science B.V. All rights reser ved.