Umbelliferone stimulates glucose uptake; modulates gluconeogenic and nucleotide-hydrolyzing enzymes activities, and dysregulated lipid metabolic pathways in isolated psoas muscle

The ability of umbelliferone to stimulate muscle glucose uptake and its effect on glucose and fatty acid metabolism as well as nucleotide hydrolysis and cholinergic activity were investigated in isolated psoas muscles. Incubation of umbelliferone with muscles led to increase glucose uptake, elevated GSH, SOD and catalase activities, as well as depleted malondialdehyde and nitric oxide levels. It also led to decrease ATPase activity with concomitant increase in ENTPDase and 5'nucleotidiase activities. The activities of chymotrypsin and acetylcholinesterase, glycogen phosphorylase, glucose-6-phosphatase, fructose-1,6-phosphatase and lipase were also suppressed. Umbelliferone reversed the altered lipid metabolites, and deactivated pathways induced by incubation with glucose. These were however reversed in umbelliferone-incubated muscles with concomitant deactivation of steroid biosynthesis. Taken together, these results further support the antidiabetic properties of umbelliferone. Its antidiabetic mechanism involves stimulation of muscle glucose uptake, with concomitant modulation of lipid metabolism and nucleotide hydrolysis, while stalling gluconeogenesis and oxidative stress.