RRC ID 43230
Author Mitsuishi M, Miyashita K, Itoh H.
Title cGMP rescues mitochondrial dysfunction induced by glucose and insulin in myocytes.
Journal Biochem Biophys Res Commun
Abstract 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.
Volume 367(4)
Pages 840-5
Published 2008-3-21
DOI 10.1016/j.bbrc.2008.01.017
PII S0006-291X(08)00035-1
PMID 18194668
MeSH Animals Cell Line Cells, Cultured Cyclic GMP / administration & dosage* Dose-Response Relationship, Drug Glucose / administration & dosage* Insulin / administration & dosage* Insulin Resistance / physiology* Mice Mitochondria, Muscle / drug effects Mitochondria, Muscle / metabolism* Muscle Fibers, Skeletal / drug effects Muscle Fibers, Skeletal / metabolism* Reactive Oxygen Species / metabolism*
IF 2.985
Times Cited 30
WOS Category BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells