Dendrobium officinale polysaccharide attenuates type 2 diabetes mellitus via the regulation of PI3K/Akt-mediated glycogen synthesis and glucose metabolism

•DOP alleviated hyperglycemia, insulin resistance and hyperlipidemia.•DOP regulated the expression of the proteins associated with glycogen synthesis.•DOP regulated the activity of hepatic enzymes involved in glycolysis and gluconeogenesis.•DOP improved glucose metabolism disorder by activating PI3K/Akt signaling pathway both in vivo and in vitro.•DOP might be a potential natural agent for the prevention and treatment of type 2 diabetes. This study aimed to explore the therapeutic effects of Dendrobium officinale polysaccharide (DOP), an active ingredient isolated from the water extract of Dendrobium officinale, in streptozotocin (STZ)-induced type 2 diabetic BALB/c mice and its potential mechanisms. Our results showed that DOP had beneficial effects in ameliorating hyperglycemia, insulin resistance and dyslipidemia. Additionally, DOP promoted glycogen synthesis via regulating the expression of glycogen synthase kinase 3 beta (GSK-3β), glycogen synthase (GS) and glucose transporter 4 (GLUT4) in the liver or muscle. Moreover, DOP reduced the blood glucose levels via the regulation of glucose metabolizing enzyme activity including pyruvate kinase (PK), hexokinase (HK) and phosphoenolpyruvate carboxykinase (PEPCK) in the liver. Furthermore, mechanistic studies illustrated that DOP could up-regulate the expression of PI3K/Akt signaling proteins both in vivo and in vitro. Our findings revealed that DOP improves glucose metabolism disorder by promoting glycogen synthesis and regulating the activity of glucose metabolism enzymes.