Androgen Receptor Network Collapse as a Driver of Sarcopenia and Multi‐Organ Metabolic Dysfunction: Implications for Organ Crosstalk in Glucose Homeostasis and Diabetes Pathogenesis

ABSTRACT Age‐related sarcopenia and late‐onset hypogonadism are increasingly recognized as interconnected drivers of metabolic dysfunction. According to the androgen receptor (AR)‐centric feed‐forward mechanism proposed in this review, decreasing testosterone levels induce receptor instability, followed by proteasomal degradation and sustained epigenetic silencing of AR, ultimately impairing anabolic signaling and promoting progressive muscle atrophy. Beyond its structural purpose, skeletal muscle serves as an endocrine organ that communicates with the pancreas, liver, and adipose tissue to control glucose homeostasis. These inter‐organ communication pathways are disrupted by AR network collapse, which increases inflammation, insulin resistance, hepatic gluconeogenesis, β‐cell stress, and metabolic rigidity. All of these pathways point to skeletal muscle AR failure as a key factor in the pathophysiology of diabetes and glucose dysregulation.