Inhibition of gluconeogenesis in cultured chicken embryo hepatocytes by Fusarium metabolites

Four Fusarium metabolites, 2,5-anhydro-D-mannitol, 2,5-anhydro-D-sorbitol, moniliformin, and fumonisin B1, were tested for their ability to inhibit gluconeogenesis and cell viability in a primary chicken embryo hepatocyte culture system. The hepatocyte system was established from fertilized chicken eggs that were incubated for 14 days. The hepatocytes produced and secreted glucose into the supernatant of a Krebs incubation solution amended with 3 mM of either lactate or fructose as a precursor for glucose formation. 2,5-Anhydro-D-mannitol and 2,5-anhydro-D-sorbitol inhibited gluconeogenesis in these cells from both lactate and fructose. The former anhydro sugar was more inhibitory when lactate was the precursor (50% inhibition, IC50, 6 mM) and the latter anhydro sugar more inhibitory when fructose was the precursor (IC50, 12 mM). Moniliformin was more inhibitory to glucose formation from lactate (IC50, 100 microM) than from fructose in these cells. The degrees of inhibition of gluconeogenesis by the two anhydro sugars and moniliformin were greater than their effect on cell viability. Fumonisin B1 as high as 1 mM neither inhibited gluconeogenesis, nor affected cell viability.