title: Role of the Insulin-Like Growth Factor Type 1 Receptor in the Pathogenesis of Diabetic Encephalopathy.
abstract: 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.
authors.affiliation: Department of Radiology, Affiliated Hospital of BeiHua University, JiLin 132011, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Zhang
authors.affiliation: College of Basic Medical Sciences, Changchun University of Chinese Medicine, Changchun, Jilin 130117, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Radiology, Affiliated Hospital of BeiHua University, JiLin 132011, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Meng