Research Progress on Causes and Mechanisms of Brain Insulin Resistance

WANG Xizhong; RUAN Caishun; WANG Yunqi; DUAN Tingjin

doi:10.3969/j.issn.2096-305X.2025.05.018

Abstract：Brain insulin resistance is characterized by the weakened effect of insulin in the brain,and is regarded as a common pathological feature of metabolic disorders and neurodegenerative diseases.To explore the causes and pathological mechanisms of brain insulin resistance,we collected and analyzed the literature on brain insulin resistance in the PubMed database from 1946 to 2024.The result shows that apart from a small amount produced by some brain tissues,most of the insulin in the brain enters through the blood-brain barrier under the regulation of receptors;the lack of insulin in the brain due to insulin receptor resistance and reduced permeability of the blood-brain barrier,as well as the reduced insulin sensitivity of brain tissues themselves,are the two main manifestations of brain insulin resistance;the molecular mechanisms regulating the formation of brain insulin resistance involve multiple aspects such as inflammatory factors,oxidative stress,microtubule-associated protein Tau,glycogen synthase kinase 3β,sugar transporters 4,and neurotoxic substances;from a macroscopic perspective,behavioral factors such as high-sugar and high-fat diets,as well as tissue lesions such as fatty liver,aging,and brain trauma,can also lead to the situation of brain insulin resistance.This study systematically explored the formation mechanism,molecular mechanism and main regulatory factors of brain insulin resistance,aiming to provide a theoretical basis for future targeted intervention of brain insulin resistance to address metabolic disorders or related brain function diseases.