Exercise Suppresses Insulin Resistance: A Potential Mechanism for Improving the Interaction Between Type 2 Diabetes and Alzheimer’s Disease

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, hyperinsulinemia, and impaired insulin sensitivity. Although classified as a metabolic disorder, T2DM also contributes to cognitive decline. Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. T2DM is strongly associated with AD and is considered a major risk factor for its development. AD is therefore recognized as a metabolic disorder mediated by cerebral insulin resistance, often termed "type 3 diabetes". T2DM and AD exhibit crosstalk, sharing overlapping molecular mechanisms including insulin resistance, mitochondrial dysfunction, oxidative stress, chronic inflammation, autophagy dysregulation, tau hyperphosphorylation, and β-amyloid deposition. Among these, insulin resistance may play a potential role in this interplay. As a non-pharmacological intervention, exercise demonstrates distinct advantages in preventing and managing metabolic and neurological disorders. Exercise maintains glucose homeostasis by mitigating insulin resistance, enhances insulin sensitivity, and concurrently reduces tau hyperphosphorylation and β-amyloid aggregation, thereby improving cognitive function. Building on current literature, this review explores how exercise mitigates insulin resistance to prevent and manage both T2DM and AD. It further proposes that insulin resistance may serve as a potential mechanistic link through which exercise modulates the pathological crosstalk between the two disorders.