Phycocyanin Protects against High Glucose High Fat Diet Induced Diabetes in Mice and Participates in AKT and AMPK Signaling

Phycocyanin is a type of marine natural product and functional food additive. Studies have demonstrated that phycocyanin has potential regulatory effects on glycometabolism, while its function and mechanism, especially in type 2 diabetes mellitus (T2DM), is still unclear. The aim of this study was to investigate the antidiabetic roles and underlying mechanism of phycocyanin in a high glucose high fat diet induced model of T2MD in C57BL/6N mice and a high-insulin-induced insulin-resistant model of SMMC-7721 cells. The results indicated that phycocyanin reduced high glucose high fat diet induced hyperglycemia as well as ameliorated glucose tolerance and histological changes in the liver and pancreas. Meanwhile, phycocyanin also significantly decreased the diabetes-induced abnormal serum biomarker variations, including triglyceride (TG), total cholesterol (TC), aspartate transaminase (AST), and glutamic-pyruvic transaminase (ALT), and increased the superoxide dismutase (SOD) content. Furthermore, the antidiabetic function of phycocyanin was exerted through activating the AKT and AMPK signaling pathway in the mouse liver, which was also verified in the insulin-resistant SMMC-7721 cells due to increased glucose uptake and activated AKT and AMPK alpha expression. Thus, the present study is the first to indicate that phycocyanin mediates antidiabetic function via activating the AKT and AMPK pathway in high glucose high fat diet induced T2DM mice and insulin-resistant SMMC-7721 cells, which lays a scientific theoretical basis for the potential treatment of diabetes and the utilization of marine natural products.