PKC delta has been shown to be activated by insulin and to interact with insulin receptor and IRS. PKB(Akt) plays an important role in glucose transport and glycogen synthesis. In this study, we investigated the possibility that PKC delta may be involved in insulin-induced activation of PKB. Studies were conducted on primary cultures of rat skeletal muscle. PKB was activated by insulin stimulation within 5 min and reached a peak by 15-30 min. Insulin also increased the physical association between PKC delta with PKB and with PDK1. The insulin-induced PKC delta-PKB association was PI3K dependent. PKB-PKC delta association was accounted for by the involvement of PDk1. Overexpression of dominant negative PKC delta abrogated insulin-induced association of PKC delta with both PKB and PDK1. Blockade of PKC delta also decreased insulin-induced Thr308 PKB phosphorylation and PKB translocation. Moreover, PKC delta inhibition reduced insulin-induced GSK3 phosphorylation. The results indicate that insulin-activated PKC delta interacts with PDK1 to regulate PKB. (c) 2006 Elsevier Inc. All rights reserved.