Chlorogenic acid and β-glucan from highland barley grain ameliorate β-cell dysfunction via inhibiting apoptosis and improving cell proliferation

Recent studies have reported that highland barley as a whole grain diet has anti-hyperglycemic effects, however little information is available about the active compounds that ameliorate pancreatic β-cell dysfunction and the related mechanisms. In this study, chlorogenic acid (CA) and β-glucan (BG) were identified as the active compounds that ameliorated β-cell dysfunction. CA ameliorated β-cell dysfunction by inhibiting cell apoptosis and improving glucose-stimulated insulin secretion via targeting G protein-coupled receptor 40 (GPR40) and regulating the phospholipase C β (PLCβ) pathway. BG ameliorated β-cell dysfunction by improving cell proliferation via targeting mammalian target of rapamycin (mTOR) and regulating the protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. Furthermore, CA and BG improved β-cell sensitivity and pancreatic insulin secretion, and inhibited β-cell apoptosis in impaired glucose tolerance (IGT) mice. Notably, CA restored homeostasis model assessment (HOMA)-β values and Ca2+-ATP and K+-ATP levels back to normal levels, and BG at 300 mg per kg BW restored β-cell insulin contents back to normal levels in IGT mice. Additionally, the combination of CA and BG had an additive effect on ameliorating β-cell dysfunction. These results help develop whole highland barley grain as a functional food for preventing type 2 diabetes by ameliorating pancreatic β-cell damage.