PPARGC1A and type 2 diabetes mellitus: Interestingly, another study in UCD-T2DM rats showed that with the progression of brain insulin resistance, AMPK phosphorylation and SIRT levels in hippocampal neurons decreased, and mitochondrial biogenesis-related PGC-1α and TFAM expressions were significantly decreased, leading to increased lipid peroxidation and decreased synaptic plasticity in hippocampal neurons [138].