Frontiers in Endocrinology (Jun 2023)

Cognitive dysfunction in diabetes: abnormal glucose metabolic regulation in the brain

  • Shan Zhang,
  • Yueying Zhang,
  • Zhige Wen,
  • YaNan Yang,
  • Tianjie Bu,
  • Xiangwei Bu,
  • Qing Ni

DOI
https://doi.org/10.3389/fendo.2023.1192602
Journal volume & issue
Vol. 14

Abstract

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Cognitive dysfunction is increasingly recognized as a complication and comorbidity of diabetes, supported by evidence of abnormal brain structure and function. Although few mechanistic metabolic studies have shown clear pathophysiological links between diabetes and cognitive dysfunction, there are several plausible ways in which this connection may occur. Since, brain functions require a constant supply of glucose as an energy source, the brain may be more susceptible to abnormalities in glucose metabolism. Glucose metabolic abnormalities under diabetic conditions may play an important role in cognitive dysfunction by affecting glucose transport and reducing glucose metabolism. These changes, along with oxidative stress, inflammation, mitochondrial dysfunction, and other factors, can affect synaptic transmission, neural plasticity, and ultimately lead to impaired neuronal and cognitive function. Insulin signal triggers intracellular signal transduction that regulates glucose transport and metabolism. Insulin resistance, one hallmark of diabetes, has also been linked with impaired cerebral glucose metabolism in the brain. In this review, we conclude that glucose metabolic abnormalities play a critical role in the pathophysiological alterations underlying diabetic cognitive dysfunction (DCD), which is associated with multiple pathogenic factors such as oxidative stress, mitochondrial dysfunction, inflammation, and others. Brain insulin resistance is highly emphasized and characterized as an important pathogenic mechanism in the DCD.

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