Therefore, fat-induced hepatic insulin resistance may be due to activation of the protein kinase C (PKC)-epsilon and/or c-Jun N-terminal kinase-1, highly expressed in liver, which may in turn lead to impaired insulin receptor substrate (IRS)-1 and IRS-2 tyrosine phosphorylation by the insulin receptor kinase (IRTK). The gene discussed is IRS1; the disease is Insulin resistance.