title: Berberine treatment prevents cardiac dysfunction and remodeling through activation of 5'-adenosine monophosphate-activated protein kinase in type 2 diabetic rats and in palmitate-induced hypertrophic H9c2 cells.
abstract: Diabetic cardiomyopathy is the major cause of death in type 2 diabetic patients. Berberine is an isoquinoline alkaloid extract from traditional chinese herbs and its hypoglycemic and hypolipidemic effects make it a promising drug for treatment of type 2 diabetes. We examined if berberine improved cardiac function and attenuated cardiac hypertrophy and fibrosis in high fat diet and streptozotocin induced-type 2 diabetic rats in vivo and reduced expression of hypertrophy markers in palmitate-induced hypertrophic H9c2 cells in vitro. Treatment of diabetic animals with berberine partially improved cardiac function and restored fasting blood insulin, fasting blood glucose, total cholesterol, and triglyceride levels to that of control. In addition, berberine treatment of diabetic animals increased cardiac 5'-adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B (AKT) activation and reduced glycogen synthase kinase 3 beta (GSK3β) activation compared to control. Palmitate incubation of H9c2 cells resulted in cellular hypertrophy and decreased expression of alpha-myosin heavy chain (α-MHC) and increased expression of beta-myosin heavy chain (β-MHC) compared to controls. Berberine treatment of palmitate-incubated H9c2 cells reduced hypertrophy, increased α-MHC expression and decreased β-MHC expression. In addition, berberine treatment of palmitate-incubated H9c2 cells increased AMPK and AKT activation and reduced GSK3β activation. The presence of the AMPK inhibitor Compound C attenuated the effects of berberine. The results strongly indicate that berberine treatment may be protective against the development of diabetic cardiomyopathy.
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China; Department of Pharmacology and Therapeutics, Biochemistry and Medical Genetics, Center for Research and Treatment of Atherosclerosis, University of Manitoba, DREAM Children's Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
authors.forename: Zhaojie
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yao
authors.affiliation: Department of Pharmacology and Therapeutics, Biochemistry and Medical Genetics, Center for Research and Treatment of Atherosclerosis, University of Manitoba, DREAM Children's Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada R3E 0T6.
authors.forename: Grant M
authors.initials: GM
authors.lastname: Hatch
authors.affiliation: Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun 130021, China. Electronic address: chen_lab@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D058065:Diabetic Cardiomyopathies / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D004789:Enzyme Activation / Q000187:drug effects; D005355:Fibrosis; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000473:pathology*; D010168:Palmitates / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D010168:Palmitates; D001599:Berberine; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Berberine; Cardiac function; Diabetes; Hypertrophy