The citrus fruit flavonoid naringenin suppresses hepatic glucose production from Fao hepatoma cells.
Hepatic gluconeogenesis is the major source of fasting hyperglycemia. Here, we investigated the role of the citrus fruit flavonoid naringenin, in the attenuation of hepatic glucose production from hepatoma (Fao) cells. We show that naringenin, but not its glucoside naringin, suppresses hepatic glucose production. Furthermore, unlike insulin-mediated suppression of hepatic glucose production, incubation of hepatocytes with the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor Ly294002 had no effect on the ability of naringenin to suppress hepatic glucose production. Further, naringenin did not increase phosphorylation of Akt at Ser473 or, Thr308, indicating this down-stream target of PI3-kinase is also not a player in naringenin-mediated suppression of hepatic glucose production. Importantly, like the dimethylbiguanide, metformin, naringenin significantly decreased cellular ATP levels without increasing cell cytotoxicity. Together, these results suggest that the aglycone, naringenin, has a role in the attenuation of hyperglycemia and may exert this effect in a manner similar to the drug, metformin.
Purushotham
Aparna
A
Department of Human Nutrition, The Ohio State University, Columbus, OH 43210, USA.
Tian
Min
M
Belury
Martha A
MA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000235:genetics; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D008687:Metformin / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D051381:Rats; D015398:Signal Transduction
D044950:Flavanones; D007004:Hypoglycemic Agents; D008687:Metformin; D019869:Phosphatidylinositol 3-Kinases; D005952:Glucose-6-Phosphatase; D010729:Phosphoenolpyruvate Carboxykinase (GTP); C005273:naringenin; D005947:Glucose