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

Life Sci. 2014 Jun 27;107(1-2):42-9. doi: 10.1016/j.lfs.2014.04.034. Epub 2014 May 5.

Abstract

Aims: 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.

Main 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.

Key findings: 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.

Significance: 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.

Keywords: AMP-activated protein kinase; C-Jun N-terminal kinase; Compound K; Type 2 diabetes; β-cell apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors*
  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Apoptosis / drug effects*
  • Blood Glucose / analysis
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cells, Cultured
  • Cholesterol / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / etiology
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diet, High-Fat
  • Ginsenosides / pharmacology*
  • Glucose Tolerance Test
  • Insulin / blood
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Palmitates / pharmacology
  • Phosphorylation / drug effects

Substances

  • Blood Glucose
  • Ginsenosides
  • Insulin
  • Palmitates
  • Cholesterol
  • ginsenoside M1
  • JNK Mitogen-Activated Protein Kinases
  • AMP-Activated Protein Kinases
  • Casp3 protein, mouse
  • Caspase 3