Adipokine dysregulation and oxidative stress in type 2 diabetes: Implications for neurodegeneration and neuroprotective eff ects of antidiabetic therapies.

Abstract

Neurodegeneration is accelerated by Type 2 diabetes mellitus through adipokine dysregulation, insulin resistance, oxidative stress, and neuroinfl ammation. This could link metabolic imbalance to Alzheimer's disease, Parkinson's disease, and cognitive decline. The aim of this review is to clarify the roles of adipokines in type 2 diabetes-induced neurodegeneration, their molecular pathways, and the possible neuroprotective potential of antidiabetic agents. Literature was searched in PubMed, Google Scholar, and Scopus for Englishlanguage articles published up to November 2025, using keywords like adipokines, diabetes mellitus, neurodegeneration, neuroinfl ammation, and antidiabetics. Results highlight those elevated levels of pro-infl ammatory adipokines, such as TNF-α, IL-6, and resistin, together with reduced levels of neuroprotective adipokines, including adiponectin and leptin, may drive NF-kB activation, suppression of Nrf2 signaling, and amyloid and tau pathology. This is further exacerbated by oxidative stress and mitochondrial dysfunction. Antidiabetic agents like metformin, GLP-1 agonists, thiazolidinediones, and SGLT2 inhibitors restore adipokine balance, enhance AMPK/PPARγ signaling, and show cognitive benefi ts in mild cognitive impairment cohorts per clinical trials. In conclusion, repurposing antidiabetics via biomarker-guided multiple therapies off ers disease-modifying promise for type 2 diabetes-linked neurodegeneration, necessitating large randomized controlled trials in prediabetic populations. (Neuropsychopharmacol Hung 2026; 28(2): 102-114) Keywords: Adipokines, Type 2 diabetes mellitus, Neurodegeneration, Neuroinfl ammation, Antidiabetic agents.