Monascus-fermented grain vinegar enhances glucose homeostasis through the IRS-1/PI3K/Akt and AMPK signaling pathways in HepG2 cell and db/db mice.

MV was reported to have beneficial effects in ameliorating insulin resistance in db/db mice, but the intrinsic mechanisms for glucose homeostasis are unclear. This study examined the anti-diabetic mechanism of MV using HepG2 cells and C57BL/KsJ-db/db mice. MV increased insulin sensitivity by promoting insulin-dependent glucose uptake and activating glycogen accumulation in HepG2 cells. Furthermore, the glucose homeostasis was enhanced in db/db mice administered 1 mg/kg/day of MV for eight weeks by activating the IRS-1/PI3K/Akt and AMPK pathways in the skeletal muscle and liver tissue. In addition, MV promoted glycogen synthesis by regulating the key enzymes, including GSK-3ß and GS, and suppressed gluconeogenesis by inhibiting the mRNA expressions of G6pase and PEPCK. These findings show that MV regulates both signaling pathways and improves the glucose metabolism disorder. Thus, MV might be an alternative functional food or nutraceutical in ameliorating T2DM. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01146-4.