Baicalin ameliorates hepatic insulin resistance and gluconeogenic activity through inhibition of p38 MAPK/PGC-1α pathway

Background: Although the results of our and other studies show that baicalin can enhance glucose uptake and insulin sensitivity in skeletal muscle and adipocytes of mice, the specific metabolic contribution of baicalin on hepatic insulin resistance and gluconeogenic activity is still unclear. Purpose: The aim of this study is to investigate whether baicalin is involved in regulation of hepatic insulin resistance and gluconeogenic activity and its underlying mechanisms. Study Design/Methods: In the present study, high-fat diet-induced obese mice were given 50 mg/kg baicalin intraperitoneally (i.p.) once a day for 21 consecutive days, and hepatocytes were treated with baicalin (100 mu M) or metformin (100 mu M) in the presence of glucagon (200 nM) for 12 h. Then insulin resistance indexes and genes related to gluconeogenesis were examined in liver tissues. Results: The present findings showed that baicalin decreased body weight, HOMA-IR, and alleviated high fat diet-induced glucose intolerance, hyperglycemia and insulin resistance in diet-induced obese mice. Furthermore, baicalin markedly suppressed p-p38 MAPK, p-CREB, FoxO1, PGC-1 alpha, PEPCK and G6Pase expression in liver of obese mice and hepatocytes. Moreover, inhibition of gluconeogenic genes by baicalin was also strengthened by p38MAPK inhibitor in hepatocytes. Conclusion: Baicalin suppressed expression of PGC-1a and gluconeogenic genes, and reduced glucose production in high-fat diet-induced obese mice. Baicalin ameliorated hepatic insulin resistance and gluconeogenic activity mainly through inhibition of p38 MAPK/PGC-1 alpha signal pathway. This study provides a possibility of using baicalin to treat hyperglycemia and hepatic insulin resistance in clinic.