Role of the Insulin-Like Growth Factor Type 1 Receptor in the Pathogenesis of Diabetic Encephalopathy.

Duo Zhang,Heng Meng,Shuang Jiang

doi:10.1155/2015/626019

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-1Rneo) 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.

Highlights

The case reports are presented in the order of increasing severity of the neuropathological changes [1, 2]
We show that PC-12 cells lacking the insulin-like growth factor type 1 receptor (IGF-1R) are two to three times more sensitive to insulin than are cells expressing both receptors
It is concluded that insulin exerts direct anabolic actions in neuron-like cells by activation of its cognate receptor; the solid data provided in the study proves that IGF-1R plays an important role of in the pathogenesis of diabetic encephalopathy (DE)

Summary

Introduction

The case reports are presented in the order of increasing severity of the neuropathological changes [1, 2]. The severe damage found on histological examination of the brains from the patients justifies the term encephalopathy [3,4,5]. Diabetes and its treatment are associated with functional and structural disturbances in the brain [8,9,10]. Many existing publications focused on changes in cerebral function and structure that develop more insidiously [10]. These changes are referred to as diabetic encephalopathy (DE), a term that encompasses functional impairment of cognition, cerebral signal conduction, neurotransmission and synaptic plasticity, and underlying structural pathology associated with diabetes [11,12,13,14]

Methods

Results

Conclusion