Defective cognitive function is common in patients with diabetes, suggesting that
insulin normally exerts anabolic actions in neuron, namely,
diabetic encephalopathy. However, because
insulin can cross-activate the
insulin-like growth factor type 1 receptor (IGF-1R), which also functions in most of tissues, such as muscle and bone, it has been difficult to establish the direct (IGF-1-independent) actions of
insulin in the pathogenesis of
diabetic encephalopathy. To overcome this problem, we examined
insulin signaling and action in primary PC-12 cells engineered for conditional disruption of the
IGF-1 receptor (ΔIGF-1R). The results showed that the lower
glucose metabolism and high expression of IGF-1R occurred in the brain of the DE rat model. The results also showed the defect of IGF-1R could significantly improve the ability of
glucose consumption and enhance sensitivity to
insulin-induced IR and Akt phosphorylation in PC12 cells. And meanwhile, IGF-1R allele gene knockout (IGF-1R(neo)) mice treated with HFD/STZ had better cognitive abilities than those of wild mice. Those results indicate that
insulin exerts direct anabolic actions in neuron-like cells by activation of its cognate receptor and prove that IGF-1R plays an important role in the pathogenesis of
diabetic encephalopathy.