cGMP rescues mitochondrial dysfunction induced by glucose and insulin in myocytes.
Mitochondrial dysfunction in the skeletal muscle has been implicated in a wide variety of pathological processes including insulin resistance in type 2 diabetes. A recent report indicates that calorie restriction can modulate mitochondrial function through the nitric oxide/cGMP-dependent pathway. Following up on these findings, we examined whether cGMP could rescue mitochondrial dysfunction in C2C12 myotubular cells induced by conditions of high-glucose and high-insulin. Treatment of the cells with cGMP promoted mitochondrial biogenesis and ATP synthesis without enhancing production of reactive oxygen species (ROS) in association with up-regulation of the genes involved in oxidative phosphorylation and ROS reduction. The increased mitochondria were revealed to have lower membrane potential, which is similar to the effect of calorie restriction, and reversed mitochondrial dysfunction caused by high-glucose and high-insulin. These results indicated that augmented cGMP-dependent cascades in the skeletal muscle may attenuate insulin resistance observed in patients with type 2 diabetes and metabolic syndrome.
Mitsuishi
Masanori
M
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinano-machi, Research Park 5N8, Shinjuku-ku, Tokyo 160-8582, Japan.
Miyashita
Kazutoshi
K
Itoh
Hiroshi
H
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
D007328:Insulin; D017382:Reactive Oxygen Species; D006152:Cyclic GMP; D005947:Glucose