Effects of streptozocin-induced diabetes and islet cell transplantation oninsulin signaling in rat skeletal muscle

Streptozocin-induced diabetes is associated with alterations in insulin sig naling in rat skeletal muscle, including increased insulin receptor substra te-1 phosphorylation and phosphotidylinositol 3-kinase activity. In the cur rent study, we determined the effects of streptozocin-induced diabetes and treatment of diabetes by islet cell transplantation on several proximal ins ulin-activated signaling proteins. Three groups of male Lewis rats (untreat ed streptozocin-diabetic animals, islet cell-transplanted diabetic rats, an d nondiabetic control rats) were studied in the basal state or 30 min after ip insulin injection (20 U/rat). Mixed hindlimb skeletal muscle lysates we re used to determine the expression and enzymatic activities of the extrace llular regulated kinase 2 (ERK2), p90 ribosomal S6 kinase (RSK2), Akt, and p70 S6 kinase (p70<SUP>S6k</SUP>). In all three groups of rats, insulin sig nificantly increased ERK2, RSK2, Akt, and p70<SUP>S6k</SUP> activities.<SUP ></SUP> There was no effect of diabetes on insulin-stimulated ERK2 activity or ERK2 protein levels. RSK2 expression and insulin-stimulated RSK2 activi ty were significantly elevated in diabetic rats compared with those in the control animals. Insulin-stimulated Akt activity was also significantly gre ater in the diabetic animals, but there was no change in protein expression . In contrast, there was a decrease in insulin-stimulated p70<SUP>S6k</SUP> activity With no change in protein expression in the diabetic rats. Islet transplantation partially (RSK2) or fully (Akt, p70<SUP>S6k</SUP>) normaliz ed these diabetes-induced changes in insulin signaling proteins. We conclud e that streptozocin diabetes results in the dysregulation of several critic al insulin-activated proteins in rat skeletal muscle, but islet cell transp lantation is an effective therapy to partially correct these alterations in insulin signaling.