Mice bearing targeted gene mutations that affect insulin receptor (Insr) function have
contributed important new information on the pathogenesis of type 2 diabetes. Whereas
complete Insr ablation is lethal, conditional mutagenesis in selected tissues has more limited
consequences on metabolism. Studies of mice with tissue-specific ablation of Insr have
indicated that both canonical (eg muscle and adipose tissue) and noncanonical (eg liver,
pancreatic β-cells, and brain) insulin target tissues can contribute to insulin resistance, albeit …