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

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 (INK) pathway. Main methods: Treatment effect of CK on type 2 diabetic (T2D) mice and palmitate-induced MIN6 beta-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 beta-cell viability, apoptosis and caspase-3 activity and activation of AMPK and INK 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 beta-cell apoptosis via inhibition of the AMPK-JNK pathway. (C) 2014 Elsevier Inc. All rights reserved.