Osthole enhances glucose uptake through activation of AMP-activated protein kinase in skeletal muscle cells.

Abstract

AMP-activated protein kinase (AMPK) is an energy sensor that regulates cellular metabolism. Activation of AMPK in skeletal muscles, the liver, and adipose tissues results in a favorable metabolic milieu for preventing and treating type 2 diabetes, i.e., decreased levels of circulating glucose, plasma lipids, and ectopic fat accumulation and enhanced insulin sensitivity. Osthole was extracted from a Chinese herbal medicine, and we found that it had glucose lowering activity in our previous study. However, the detailed glucose lowering mechanisms of osthole are still unclear. In this study, we used skeletal muscle cells to examine the underlying molecular mechanisms of osthole's glucose lowering activity. A Western blot analysis revealed that osthole significantly induced phosphorylation of AMPK and acetyl-CoA carboxylase (ACC). Next, we found that osthole significantly increased the level of translocation of glucose transporter 4 (GLUT4) to plasma membranes and glucose uptake in a dose-dependent manner. Osthole-induced glucose uptake was reversed by treatment with Compound C, an AMPK inhibitor, suggesting that osthole-induced glucose uptake was mediated in an AMPK-dependent manner. The increase in the AMP:ATP ratio was involved in osthole's activation of AMPK. Finally, we found that osthole counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that the increase in the AMP:ATP ratio by osthole triggered activation of the AMPK signaling pathway and led to increases in plasma membrane GLUT4 content and glucose uptake level. Therefore, osthole might have potential as an antidiabetic agent for treating diabetes.

• Authors: Wei-Hwa Lee, Ren-Jye Lin, Shyr-Yi Lin, Yu-Chien Chen, Hsiu-Ming Lin, Yu-Chih Liang
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 59 Issue 24 Pg. 12874-81 (Dec 28 2011) ISSN: 1520-5118 [Electronic] United States
• PMID: 22098542 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Coumarins
• Glucose Transporter Type 4
• Hypoglycemic Agents
• AMP-Activated Protein Kinases
• Acetyl-CoA Carboxylase
• Glucose
• osthol

Topics

• AMP-Activated Protein Kinases (metabolism)
• Acetyl-CoA Carboxylase (metabolism)
• Animals
• Blood Glucose (analysis)
• Cell Line
• Cnidium (chemistry)
• Coumarins (pharmacology, therapeutic use)
• Diabetes Mellitus, Experimental (blood, drug therapy)
• Enzyme Activation (drug effects)
• Glucose (metabolism)
• Glucose Transporter Type 4 (metabolism)
• Hep G2 Cells
• Humans
• Hyperglycemia (drug therapy)
• Hypoglycemic Agents
• Male
• Mice
• Mice, Inbred ICR
• Muscle, Skeletal (drug effects, enzymology, metabolism)
• Phosphorylation (drug effects)
• Taiwan