Proanthocyanidins from Chinese dwarf cherry [ <i>Cerasus humilis</i> (Bge.) Sok.] pomace ameliorate hepatic glucose-lipid metabolism abnormalities in T2DM mice via PI3K/Akt/FoxO1 and AMPK/ACC signaling pathways

Background Chinese dwarf cherry ( Cerasus humilis ) pomace is rich in proanthocyanidins, which exhibit antidiabetic activity. Objective This study investigates the protective effect of proanthocyanidins extracted from C. humilis pomace by regulating hepatic glucose-lipid metabolism in streptozotocin (STZ)-induced type 2 diabetic mellitus (T2DM) mice fed a high-fat diet (HFD). Methods The antidiabetic activities of Cerasus humilis pomace proanthocyanidins (CPPs) were evaluated through fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and biochemical analysis, including AST, ALT, C-peptide, and hepatic glycogen in mouse serum, TC, TG, HDL-C, and LDL-C levels in the liver, as well as MDA and SOD levels. Thereafter, transcriptomic analysis, coupled with western blot and RT-qPCR, was employed to validate the molecular mechanism by which CPPs improved T2DM pathology in mice. Results CPPs significantly attenuated body weight gain, hyperglycemia, hepatic lipid accumulation, and liver injury in T2DM mice. Transcriptomics implicated the PI3K/Akt/FoxO1 and AMPK/ACC signaling pathways in mediating CPPs’ anti-diabetic effects. Subsequently, western blot, immunohistochemistry, and RT-qPCR analyses confirmed that CPPs regulate these pathways and demonstrated significant suppression of key gluconeogenic enzymes, PEPCK and G6Pase. Conclusion CPPs can effectively ameliorate T2DM by suppressing hepatic glucolipid metabolism abnormalities, primarily through regulation of the PI3K/Akt/FoxO1 and AMPK/ACC signaling pathways.