Procyanidin B1 and p‐Coumaric Acid from Highland Barley Grain Showed Synergistic Effect on Modulating Glucose Metabolism via IRS‐1/PI3K/Akt Pathway

Introduction Phenolic extract in highland barley grain has showed hypoglycemic effect, while little information is available about the active compounds and whether there exist additive or synergistic effect on modulating glucose metabolism. Methods and Results Procyanidin B1 (PB) and p‐coumaric acid (CA) are the active compounds in highland barley grain and show synergistic effect on improving glucose uptake and glycogen synthesis by upregulating glucose transporter (GLUT4) and downregulating glycogen synthase kinase‐3β (GSK‐3β) protein expression, respectively. The mechanism may be attributed to target insulin receptor (IRβ) and regulate insulin receptor substrate‐1 (IRS‐1)/phosphatidylinositol 3‐kinase (PI3K)/ protein kinase B (Akt) pathway. Furthermore, PB + CA exhibits synergistic effect on restoring glucose intolerance and insulin resistance, and improving hepatic glycogen synthesis in impaired glucose tolerance (IGT) mice. The postprandial blood glucose (PBG), homeostasis model assessment (HOMA)‐IR values and serum insulin contents in PB + CA‐treated IGT mice with dosage of 300 mg kg ‐1 BW are reversed to normal levels. Additionally, PC + CA shows additive effect on inhibiting gluconeogenesis in vitro and in vivo. Conclusion PB + CA in highland barley grain synergistically modulate glucose metabolism. These results may provide evidence of whole highland barley grain diet achieve superior effect on restoring IGT than isolated components.