title: Baicalin attenuates high fat diet-induced insulin resistance and ectopic fat storage in skeletal muscle, through modulating the protein kinase B/Glycogen synthase kinase 3 beta pathway.
abstract: Insulin resistance is the pathophysiological basis of many diseases. Overcoming early insulin resistance highly significant in prevention diabetes, non-alcoholic fatty liver, and atherosclerosis. The present study aimed at evaluating the therapeutic effects of baicalin on insulin resistance and skeletal muscle ectopic fat storage in high fat diet-induced mice, and exploring the potential molecular mechanisms. Insulin resistance in mice was induced with a high fat diet for 16 weeks. Animals were then treated with three different doses of baicalin (100, 200, and 400 mg·kg(-1)·d(-1)) for 14 weeks. Fasting blood glucose, fasting serum insulin, glucose tolerance test (GTT), insulin tolerance test (ITT), and skeletal muscle lipid deposition were measured. Additionally, the AMP-activated protein kinase/acetyl-CoA carboxylase and protein kinase B/Glycogen synthase kinase 3 beta pathways in skeletal muscle were further evaluated. Baicalin significantly reduced the levels of fasting blood glucose and fasting serum insulin and attenuated high fat diet induced glucose tolerance and insulin tolerance. Moreover, insulin resistance was significantly reversed. Pathological analysis revealed baicalin dose-dependently decreased the degree of the ectopic fat storage in skeletal muscle. The properties of baicalin were mediated, at least in part, by inhibition of the AMPK/ACC pathway, a key regulator of de novo lipogenesis and activation of the Akt/GSK-3β pathway, a key regulator of Glycogen synthesis. These data suggest that baicalin, at dose up to 400 mg·kg(-1)·d(-1), is safe and able to attenuate insulin resistance and skeletal muscle ectopic fat storage, through modulating the skeletal muscle AMPK/ACC pathway and Akt/GSK-3β pathway.
authors: Department of Pharmacology, Medical School, Southeast University, Nanjing 210009, China; Department of Pharmacy, Affiliated Drum Tower Hospital of Nanjing University, Nanjing 210008, China.
authors: You-Li
authors: YL
authors: Xi
authors: Department of Pharmacology, Medical School, Southeast University, Nanjing 210009, China.
authors: Hong-Xia
authors: HX
authors: Li
authors: Center of Medical Functional Experiment, Southeast University, Nanjing 210009, China.
authors: Chen
authors: C
authors: Chen
authors: Department of Pharmacology, Medical School, Southeast University, Nanjing 210009, China.
authors: Ya-Qun
authors: YQ
authors: Liu
authors: Department of Pharmacology, Medical School, Southeast University, Nanjing 210009, China.
authors: Hong-Mei
authors: HM
authors: Lv
authors: Department of Pharmacology, Medical School, Southeast University, Nanjing 210009, China.
authors: Shi-Qi
authors: SQ
authors: Dong
authors: Department of Pharmacology, Medical School, Southeast University, Nanjing 210009, China.
authors: Er-Fei
authors: EF
authors: Luo
authors: Department of Pharmacology, Medical School, Southeast University, Nanjing 210009, China.
authors: Ming-Bo
authors: MB
authors: Gu
authors: Department of Pharmacology, Medical School, Southeast University, Nanjing 210009, China; Center of Medical Functional Experiment, Southeast University, Nanjing 210009, China. Electronic address: liuhua1036@163.com.
authors: Hua
authors: H
authors: Liu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D059305:Diet, High-Fat; D005419:Flavonoids / Q000494:pharmacology*; D000071679:Glycogen Synthase Kinase 3 beta / Q000502:physiology*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D005419:Flavonoids; C038044:baicalin; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase
keywords: Baicalin; Glycogen synthase kinase 3 beta; Insulin resistance; Protein kinase B; Skeletal muscle ectopic fat storage