J Gao1,2, M Liu2, Z Guo2, C Hu2, Z Feng2, J Yan2. 1. Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. 2. Cooperation Research Center of Shanghai University of Traditional Chinese Medicine//Department of Endocrinology, Traditional Chinese Medicine Hospital of Jiading District, Shanghai 201899, China.
Abstract
OBJECTIVE: To explore the role of fetuin B-AMPK/ACC signaling pathway in mediating the effect of puerarin on hepatic insulin resistance in mice with type 2 diabetes mellitus (T2DM). OBJECTIVE: Forty C57BL/6J mouse models of T2DM induced by high-fat diet and intraperitoneal injection of streptozotocin were randomized into diabetic model (HFD) group and 3 puerarin groups for treatment with low-, moderate- and high- dose puerarin (50, 100 and 200 mg/kg, respectively), with another 10 mice fed a normal diet as the control group. After treatment for 8 weeks, the mice were examined for fasting blood glucose (FBG), fasting insulin (FINS), liver triglycerides (TG), cholesterol (TC) and free fatty acids (FFA) levels. The expression of fetuin B in the liver was detected by immunohistochemistry. RT-qPCR was used to detect the expressions of fetuin B, AMPK, and ACC mRNA in the liver, and the protein expressions of fetuin B, AMPKα1, ACC, P-AMPKαT183/T172, and P-ACC S79 were determined with Western blotting. OBJECTIVE: Treatment with moderate- and high-dose puerarin significantly lowered TG, TC, FFA and FBG levels in diabetic mice (P < 0.01). Puerarin at all the 3 doses significantly lowered FINS and HOMA-IR of the mice (P < 0.01). In diabetic mice, hepatic expressions of fetuin B and ACC mRNA increased and AMPK mRNA decreased significantly (P < 0.01); the protein expressions of fetuin B and ACC increased while those of AMPKα1, P-AMPKαT183/T172 and P-ACC S79 decreased significantly (P < 0.01). Puerarin dose-dependently inhibited the mRNA and protein expressions of fetuin B and ACC, increased AMPK mRNA and protein expressions of AMPKα1, P-AMPKαT183/ T172, and P-ACC S79, and lowered fetuin B content in the liver of diabetic mice (P < 0.01). OBJECTIVE: Puerarin alleviates insulin resistance and improves glucolipid metabolism in T2DM mice by modulating hepatic fetuin B-AMPK/ACC signaling pathway.
OBJECTIVE: To explore the role of fetuin B-AMPK/ACC signaling pathway in mediating the effect of puerarin on hepatic insulin resistance in mice with type 2 diabetes mellitus (T2DM). OBJECTIVE: Forty C57BL/6J mouse models of T2DM induced by high-fat diet and intraperitoneal injection of streptozotocin were randomized into diabetic model (HFD) group and 3 puerarin groups for treatment with low-, moderate- and high- dose puerarin (50, 100 and 200 mg/kg, respectively), with another 10 mice fed a normal diet as the control group. After treatment for 8 weeks, the mice were examined for fasting blood glucose (FBG), fasting insulin (FINS), liver triglycerides (TG), cholesterol (TC) and free fatty acids (FFA) levels. The expression of fetuin B in the liver was detected by immunohistochemistry. RT-qPCR was used to detect the expressions of fetuin B, AMPK, and ACC mRNA in the liver, and the protein expressions of fetuin B, AMPKα1, ACC, P-AMPKαT183/T172, and P-ACC S79 were determined with Western blotting. OBJECTIVE: Treatment with moderate- and high-dose puerarin significantly lowered TG, TC, FFA and FBG levels in diabeticmice (P < 0.01). Puerarin at all the 3 doses significantly lowered FINS and HOMA-IR of the mice (P < 0.01). In diabeticmice, hepatic expressions of fetuin B and ACC mRNA increased and AMPK mRNA decreased significantly (P < 0.01); the protein expressions of fetuin B and ACC increased while those of AMPKα1, P-AMPKαT183/T172 and P-ACC S79 decreased significantly (P < 0.01). Puerarin dose-dependently inhibited the mRNA and protein expressions of fetuin B and ACC, increased AMPK mRNA and protein expressions of AMPKα1, P-AMPKαT183/ T172, and P-ACC S79, and lowered fetuin B content in the liver of diabeticmice (P < 0.01). OBJECTIVE:Puerarin alleviates insulin resistance and improves glucolipid metabolism in T2DM mice by modulating hepatic fetuin B-AMPK/ACC signaling pathway.