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. PKCα may regulate IRS activity in response to insulin. We investigated the possibility that PKCα may be important in insulin signaling. Studies were conducted on skeletal muscle in adult mice and on L6 skeletal cells. PKCα is constitutively associated with IRS-1, and insulin stimulation of PKCα causes disassociation of the two proteins within 5 min. Blockade of PKCα inhibited insulin-induced disassociation of PKCα from IRS1. Selective inhibition of PKCα increased the ability of insulin to reduce blood glucose levels. Insulin stimulation activates PKB and increases the association of PKCα with PKB. Blockade of PKCα increased threonine phosphorylation of PKB. We suggest that PKCα regulates insulin signaling in skeletal muscle through its disassociation from IRS-1 and association with PKB.