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Published on: January 23, 2018
cGMP rescues mitochondrial dysfunction induced by glucose and insulin in myocytes
Masanori Mitsuishi1, Kazutoshi Miyashita, Hiroshi Itoh
1Department of Internal Medicine, School of Medicine, Keio University, 35 Shinano-machi, Research Park 5N8, Shinjuku-ku, Tokyo 160-8582, Japan.
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.
Insights
Cyclic guanosine monophosphate (cGMP) can reverse mitochondrial dysfunction in skeletal muscle cells. This finding suggests cGMP may help treat insulin resistance in type 2 diabetes.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Research
Background:
- Mitochondrial dysfunction is linked to insulin resistance in type 2 diabetes.
- Calorie restriction impacts mitochondrial function via the nitric oxide/cGMP pathway.
Purpose of the Study:
- To investigate if cGMP can reverse high-glucose and high-insulin-induced mitochondrial dysfunction in C2C12 myotubular cells.
- To explore the effects of cGMP on mitochondrial biogenesis, ATP synthesis, and reactive oxygen species (ROS) production.
Main Methods:
- Treatment of C2C12 myotubular cells with cGMP under high-glucose and high-insulin conditions.
- Analysis of mitochondrial biogenesis, ATP synthesis, ROS production, gene expression related to oxidative phosphorylation, and mitochondrial membrane potential.
Main Results:
- cGMP treatment promoted mitochondrial biogenesis and ATP synthesis.
- ROS production was not enhanced; genes for oxidative phosphorylation and ROS reduction were upregulated.
- Increased mitochondria exhibited lower membrane potential, mimicking calorie restriction effects.
- cGMP reversed mitochondrial dysfunction caused by high-glucose and high-insulin.
Conclusions:
- Augmented cGMP-dependent pathways in skeletal muscle may mitigate insulin resistance.
- This suggests a potential therapeutic strategy for type 2 diabetes and metabolic syndrome.
