Despite the significant increase in the activation of the conventional PKC isoforms PKCα and PKCβ in FR-fed BL6 mice, hepatic insulin signalling was unaffected by FR-feeding in both strains in our study, potentially indicating that PKCɛ is indeed the critical hepatic PKC isoform that antagonises insulin signalling during the development of insulin resistance, as proposed previously9, 37, 38, 39. Here, INS is linked to Insulin resistance.