Role of astrocytes in diabetic neuropathy: Review of their involvement in disease mechanisms

Diabetes mellitus (DM) and its complications continue to impose a substantial burden on healthcare systems worldwide. Diabetic neuropathy (DN) is one of the most common chronic microvascular and neurodegenerative complications of DM. It is clinically characterized by allodynia, hyperalgesia, and abnormal or absent nerve fiber sensation, which collectively contribute to poor quality of life, sleep disturbances, depression, and increased mortality. Although several pharmacological agents are available to alleviate DN-related symptoms, their limited long-term efficacy and adverse side effects underscore the urgent need for novel therapeutic approaches. This limitation may be attributed to an incomplete understanding of the underlying mechanisms of DN. Accumulating evidence has highlighted the contribution of glial cells including astrocytes, microglia, and oligodendrocytes to the pathogenesis of DN. However, the specific role of astrocytes remains insufficiently defined. Therefore, this review provides a comprehensive evaluation of current knowledge regarding astrocyte involvement in DN mechanisms, with the goal of clarifying their contribution to disease progression and identifying potential therapeutic targets.