Intestinal transport of Monascus vinegar melanoidins and their amelioration of insulin resistance in HepG2 cells via IRS-1/PI3K/Akt and AMPK pathways

The small intestinal digestion melanoidins (IDM), a product of Monascus vinegar melanoidins (LVM) digestion, were subjected to an analysis of their transport mode in intestinal epithelial cells, as well as their effect and mechanism of mitigating insulin resistance (IR) in HepG2 cells. The results show that IDM undergoes intestinal epithelial cell transport through a transcellular pathway, involving multiple endocytic mechanisms. IDM (200 - 400 µg/mL) increased glucose uptake and consumption, promoted glycogen synthesis, and inhibited gluconeogenesis in IR-HepG2 cells. After endocytosis into HepG2 cells, IDM initiates downstream reactions by promoting IRS-1 tyrosine phosphorylation. The PI3K/Akt pathway serves as the core pathway for improving IR in HepG2 cells. Activation of the PI3K/Akt pathway enhances GLUT4 translocation to promote glucose uptake and promotes glycogen synthesis by inhibiting p-GS expression. Additionally, IDM attenuates gluconeogenesis by activating the AMPK pathway, thereby regulating the nuclear protein HNF-4α and key enzymes. In vivo, oral administration of LVM effectively improved IR and liver metabolic disorders in T2DM mice. These findings indicate that Monascus vinegar melanoidins can serve as a potential functional factor for preventing and improving IR, providing a scientific basis for the development of new functional foods and dietary additives.