Our GSEA analysis of T1D murine brain transcriptomes revealed significant enrichment of PI3K/Akt/mTOR pathway components following TREM2 ablation, a finding corroborated by biochemical assays demonstrating TREM2-dependent mTOR activation under sustained hyperglycemia without concurrent modulation of Erk1/2 or GSK3β phosphorylation states. Here, AKT1 is linked to type 1 diabetes mellitus.