cGMP rescues mitochondrial dysfunction induced by glucose and insulin in myocytes

Masanori Mitsuishi, Kazutoshi Miyashita, Hiroshi Itoh

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)840-845
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume367
Issue number4
DOIs
Publication statusPublished - 2008 Mar 21

Fingerprint

Muscle Cells
Type 2 Diabetes Mellitus
Insulin Resistance
Reactive Oxygen Species
Skeletal Muscle
Insulin
Glucose
Oxidative Phosphorylation
Organelle Biogenesis
Pathologic Processes
Medical problems
Membrane Potentials
Muscle
Mitochondria
Nitric Oxide
Up-Regulation
Adenosine Triphosphate
Genes
Cells
Association reactions

Keywords

  • Calorie restriction
  • cGMP
  • Diabetes
  • Insulin resistance
  • Mitochondria
  • Mitochondrial biogenesis
  • PGC1
  • Reactive oxygen species
  • Skeletal muscle

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

cGMP rescues mitochondrial dysfunction induced by glucose and insulin in myocytes. / Mitsuishi, Masanori; Miyashita, Kazutoshi; Itoh, Hiroshi.

In: Biochemical and Biophysical Research Communications, Vol. 367, No. 4, 21.03.2008, p. 840-845.

Research output: Contribution to journalArticle

@article{611ddda3c1c14cd784187b8f965a51a4,
title = "cGMP rescues mitochondrial dysfunction induced by glucose and insulin in myocytes",
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.",
keywords = "Calorie restriction, cGMP, Diabetes, Insulin resistance, Mitochondria, Mitochondrial biogenesis, PGC1, Reactive oxygen species, Skeletal muscle",
author = "Masanori Mitsuishi and Kazutoshi Miyashita and Hiroshi Itoh",
year = "2008",
month = "3",
day = "21",
doi = "10.1016/j.bbrc.2008.01.017",
language = "English",
volume = "367",
pages = "840--845",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - cGMP rescues mitochondrial dysfunction induced by glucose and insulin in myocytes

AU - Mitsuishi, Masanori

AU - Miyashita, Kazutoshi

AU - Itoh, Hiroshi

PY - 2008/3/21

Y1 - 2008/3/21

N2 - 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.

AB - 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.

KW - Calorie restriction

KW - cGMP

KW - Diabetes

KW - Insulin resistance

KW - Mitochondria

KW - Mitochondrial biogenesis

KW - PGC1

KW - Reactive oxygen species

KW - Skeletal muscle

UR - http://www.scopus.com/inward/record.url?scp=38749150314&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38749150314&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2008.01.017

DO - 10.1016/j.bbrc.2008.01.017

M3 - Article

VL - 367

SP - 840

EP - 845

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -