Korean Diabetes J.  2009 Jun;33(3):198-205. 10.4093/kdj.2009.33.3.198.

Nitric Oxide Increases Insulin Sensitivity in Skeletal Muscle by Improving Mitochondrial Function and Insulin Signaling

Affiliations
  • 1Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea. wjlee@amc.seoul.kr
  • 2Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.

Abstract

BACKGROUND
Accumulating evidence has suggested that nitric oxide (NO) is involved in the regulation of insulin sensitivity in skeletal muscle. Recent studies also suggested NO as an important molecule regulating mitochondrial biogenesis. This study examined the effect of the NO donor, 3-morpholinosydnonimine (SIN-1), on glucose metabolism in skeletal muscle and tested the hypothesis that NO's effect on glucose metabolism is mediated by its effect on mitochondrial function. METHODS: In Sprague-Dawley (SD) rats treated with SIN-1 for 4 weeks, insulin sensitivity was measured by a glucose clamp study. Triglyceride content and fatty acid oxidation were measured in the skeletal muscle. In addition, mitochondrial DNA content and mRNA expression of mitochondrial biogenesis markers were assessed by real-time polymerase chain reaction and expression of insulin receptor substrate (IRS)-1 and Akt were examined by Western blot analysis in skeletal muscle. In C2C12 cells, insulin sensitivity was measured by 2-deoxyglucose uptake and Western blot analysis was used to examine the expression of IRS-1 and Akt. RESULTS: SIN-1 improved insulin sensitivity in C2C12 cells and skeletal muscles of SD rats. In addition, SIN-1 decreased triglyceride content and increased fatty acid oxidation in skeletal muscle. Mitochondrial DNA contents and biogenesis in the skeletal muscle were increased by SIN-1 treatment. Moreover, SIN-1 increased the expression of phosphor-IRS-1 and phosphor-Akt in the skeletal muscle and muscle cells. CONCLUSION: Our results suggest that NO mediates glucose uptake in skeletal muscle both in vitro and in vivo by improving mitochondrial function and stimulating insulin signaling pathways.

Keyword

Insulin resistance; Mitochondria; Muscles; Nitric oxide; Signal transduction

MeSH Terms

Animals
Organelle Biogenesis
Blotting, Western
Deoxyglucose
DNA, Mitochondrial
Glucose
Glucose Clamp Technique
Humans
Insulin
Insulin Resistance
Mitochondria
Muscle Cells
Muscle, Skeletal
Muscles
Nitric Oxide
Rats
Real-Time Polymerase Chain Reaction
Receptor, Insulin
RNA, Messenger
Signal Transduction
Tissue Donors
DNA, Mitochondrial
Deoxyglucose
Glucose
Insulin
Nitric Oxide
RNA, Messenger
Receptor, Insulin
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