To examine the direct actions of insulin in diabetic encephalopathy (DE) and elucidate signaling pathways downstream of the IR, we used a model for conditional removal of the IGF-1R in vitro by adenoviral introduction of the Cre-recombinase to primary rat PC-12 cell derived from mice carrying floxed IGF-1R alleles. Here, INS is linked to diabetic encephalopathy.