title: Capsaicin stimulates glucose uptake in C2C12 muscle cells via the reactive oxygen species (ROS)/AMPK/p38 MAPK pathway.
abstract: Capsaicin has been reported to regulate blood glucose levels and to ameliorate insulin resistance in obese mice. This study demonstrates that capsaicin increases glucose uptake directly by activating AMP-activated protein kinase (AMPK) in C2C12 muscle cells, which manifested as an attenuation of glucose uptake when compound C, an AMPK inhibitor, was co-administered with capsaicin. However, the insulin signaling molecules insulin receptor substrate-1 (IRS-1) and Akt were not affected by capsaicin. Additional results showed that p38 mitogen-activated protein kinase (MAPK) is also involved in capsaicin-induced glucose transport downstream of AMPK because capsaicin increased p38 MAPK phosphorylation significantly and its specific inhibitor SB203580 inhibited capsaicin-mediated glucose uptake. Treatment with an AMPK inhibitor reduced p38 MAPK phosphorylation, but the p38 MAPK inhibitor had no effect on AMPK. Capsaicin stimulated ROS generation in C2C12 muscle cells, and when ROS were captured using the nonspecific antioxidant NAC, the increase in both capsaicin-induced AMPK phosphorylation and capsaicin-induced glucose uptake was attenuated, suggesting that ROS function as an upstream activator of AMPK. Taken together, these results suggest that capsaicin, independent of insulin, increases glucose uptake via ROS generation and consequent AMPK and p38 MAPK activations.
authors: Nutrition and Metabolism Research Group, Korea Food Research Institute, Gyeonggi-do 463-746, Republic of Korea.
authors: Soon-Hee
authors: SH
authors: Kim
authors: Jin-Taek
authors: JT
authors: Hwang
authors: Hee Sook
authors: HS
authors: Park
authors: Dae Young
authors: DY
authors: Kwon
authors: Myung-Sunny
authors: MS
authors: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000493:pharmacokinetics*; D007093:Imidazoles / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D007093:Imidazoles; D007328:Insulin; D011725:Pyridines; D017382:Reactive Oxygen Species; D055372:AMP-Activated Protein Kinases; D005947:Glucose; C093642:SB 203580; D002211:Capsaicin
keywords: AMPK; Capsaicin; Glucose uptake; ROS; p38 MAPK