Protein kinase Cα regulates insulin receptor signaling in skeletal muscle

Certain PKC isoforms are stimulated by insulin and interact with IR as well as with IRS, but it is still not clear if specific PKC isoforms regulate IR signaling directly or through IRS-1. PKC alpha may regulate IRS activity in response to insulin. We investigated the possibility that PKCa may be important in insulin signaling. Studies were conducted on skeletal muscle in adult mice and on L6 skeletal cells. PKC alpha is constitutively associated with IRS-1, and insulin stimulation of PKC alpha causes disassociation of the two proteins within 5 min. Blockade of PKCa inhibited insulin-induced disassociation of PKC alpha from IRS-1. Selective inhibition of PKC alpha increased the ability of insulin to reduce blood glucose levels. Insulin stimulation activates PKB and increases the association of PKC alpha, with PKB. Blockade of PKCa increased threonine phosphorylation of PKB. We suggest that PKC alpha regulates insulin signaling in skeletal muscle through its disassociation from IRS-1 and association with PKB. (c) 2006 Elsevier Inc. All ritlits reserved.