Ginsenoside Rb1 ameliorates the abnormal hepatic glucose metabolism by activating STAT3 in T2DM mice.

[Display omitted] • Ginsenoside Rb1 improves type 2 diabetes mellitus. • Rb1 ameliorates the abnormal hepatic glucose metabolism in T2DM mice. • Rb1 promotes glycolysis and inhibits gluconeogenesis to improve hepatic glucose metabolism. • Rb1 meliorates the abnormal hepatic glucose metabolism in a STAT3-dependent manner. Ginsenoside Rb1, a major bioactive component of Panax ginseng C. A. Mey., exerts beneficial effects on type 2 diabetes mellitus (T2DM), but its underlying mechanism is unclear. STAT3 is a key factor regulating energy metabolism. Herein, we tested whether Rb1 regulates STAT3-controlled hepatic glucose metabolism to ameliorate T2DM. Rb1 ameliorated abnormal hepatic glucose metabolism, insulin resistance, and liver steatosis in T2DM mice. Hepatic STAT3 phosphorylation was decreased in T2DM and increased after Rb1 treatment. Moreover, Rb1 reversed the decreased expressions of glycolytic enzymes and the increased expressions of gluconeogenic enzymes in T2DM. STAT3 activation increased the expressions of glycolytic enzymes and decreased the expressions of gluconeogenic enzymes in vitro , and vice versa. Further, STAT3 inhibition reversed the changes of these enzymes induced by Rb1 in insulin-resistant cells. Taken together, Rb1 ameliorated abnormal hepatic glucose metabolism in T2DM in a STAT3-dependent manner, which provides experimental bases for Rb1 in treating T2DM. [ABSTRACT FROM AUTHOR]