Camel milk exosomes regulate glucose metabolism by inhibiting mitochondrial complex I in hepatocytes

Camel milk is known to have hypoglycemic properties. Previous studies found that camel milk exosomes (CM-exo) may regulate cellular glucose metabolism through the inhibition of mitochondrial complex I, but this hypothesis has not been verified by other experiments. The

By inhibiting the activity of mitochondrial complex I in hepatocytes, CM-exo inhibited oxidative phosphorylation, oxidation of NADH to NAD+ and synthesis of ATP, enhanced glycolysis, activated AMPK and resulted in decreased gluconeogenesis and increased glycogen synthesis.

The results of this study showed that a high dose of CM-exo inhibited the viability of AML12 cells. It promoted glucose consumption, glycogen content and lactate release in AML12 cells, inhibited complex I activity, ATP content, NAD+ content, and NAD+/NADH ratio, and increased NADH content. The CM-exo increased the protein levels of p-AMPK, p-GSK3β, the protein expression ratio of p-AMPK/AMPK, p-GSK3β/GSK3β and decreased the glucose content and the protein expression levels of intracellular TET3, HNF4α-P2, PEPCK and G6PC. Conclusions: By inhibiting the activity of mitochondrial complex I in hepatocytes, CM-exo inhibited oxidative phosphorylation, oxidation of NADH to NAD+ and synthesis of ATP, enhanced glycolysis, activated AMPK and resulted in decreased gluconeogenesis and increased glycogen synthesis.