title: Compound K protects pancreatic islet cells against apoptosis through inhibition of the AMPK/JNK pathway in type 2 diabetic mice and in MIN6 β-cells.
abstract: OBJECTIVE
  Compound K (CK) is known to possess anti-diabetic activities but the mechanism for this action is unknown. The present study observed the protective effect of CK on islet cell apoptosis through the AMP-activated protein kinase (AMPK) mediated C-Jun N-terminal kinase (JNK) pathway.
  
  
  METHODS
  Treatment effect of CK on type 2 diabetic (T2D) mice and palmitate-induced MIN6 β-cells injury was observed. Fasting plasma glucose, triacylglycerol, total cholesterol, insulin levels and glucose tolerance test were evaluated. The expression of AMPK and JNK was detected in islet and MIN6 cells.
  
  
  RESULTS
  CK treatment (30 mg/kg) decreased fasting plasma glucose, triacylglycerol, total cholesterol, elevated plasma insulin levels and improved glucose tolerance in T2D mice. CK treatment attenuated islet cell apoptosis and caspase-3 activity accompanied by a decrease in AMPK and JNK activation. Meanwhile, CK treatment attenuated the palmitate-induced reduction in MIN6 β-cell viability, apoptosis and caspase-3 activity and activation of AMPK and JNK. The AMPK activator AICAR attenuated the CK-mediated inhibition of palmitate-induced apoptosis.
  
  
  CONCLUSIONS
  These data suggest that CK treatment provides a beneficial anti-diabetic effect in mice with T2D and this protective effect may be mediated through prevention of β-cell apoptosis via inhibition of the AMPK-JNK pathway.
authors.affiliation: Department of Pharmacology, Key Laboratory of Pathobiology, Ministry of Education, Basic Medicine College, Jilin University, Changchun 130021, China.
authors.forename: Feng Ying
authors.initials: FY
authors.lastname: Guan
authors.affiliation: Department of Pharmacology, Key Laboratory of Pathobiology, Ministry of Education, Basic Medicine College, Jilin University, Changchun 130021, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.affiliation: College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130018, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Key Laboratory of Pathobiology, Ministry of Education, Basic Medicine College, Jilin University, Changchun 130021, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Key Laboratory of Pathobiology, Ministry of Education, Basic Medicine College, Jilin University, Changchun 130021, China.
authors.forename: Yingshi
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Pharmacology, Key Laboratory of Pathobiology, Ministry of Education, Basic Medicine College, Jilin University, Changchun 130021, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Key Laboratory of Pathobiology, Ministry of Education, Basic Medicine College, Jilin University, Changchun 130021, China. Electronic address: chen_lab@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacology & Therapeutics, University of Manitoba, Manitoba Institute of Child Health, Winnipeg, Manitoba, Canada.
authors.forename: Grant M
authors.initials: GM
authors.lastname: Hatch
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat; D036145:Ginsenosides / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010168:Palmitates / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D055372:AMP-Activated Protein Kinases; D001786:Blood Glucose; D053148:Caspase 3; D002784:Cholesterol; D036145:Ginsenosides; D007328:Insulin; D048031:JNK Mitogen-Activated Protein Kinases; D010168:Palmitates; C112772:ginsenoside compound K; C505409:Casp3 protein, mouse
keywords: AMP-activated protein kinase; C-Jun N-terminal kinase; Compound K; Type 2 diabetes; β-cell apoptosis