Format

Send to

Choose Destination
PLoS One. 2015 May 19;10(5):e0126732. doi: 10.1371/journal.pone.0126732. eCollection 2015.

Enhanced mitochondrial superoxide scavenging does not improve muscle insulin action in the high fat-fed mouse.

Author information

1
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America.
2
Department of Physiology, East Carolina University, Greenville, North Carolina, United States of America; East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, United States of America.
3
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America; Mouse Metabolic Phenotyping Center, Vanderbilt University, Nashville, Tennessee, United States of America.

Abstract

Improving mitochondrial oxidant scavenging may be a viable strategy for the treatment of insulin resistance and diabetes. Mice overexpressing the mitochondrial matrix isoform of superoxide dismutase (sod2(tg) mice) and/or transgenically expressing catalase within the mitochondrial matrix (mcat(tg) mice) have increased scavenging of O2(˙-) and H2O2, respectively. Furthermore, muscle insulin action is partially preserved in high fat (HF)-fed mcat(tg) mice. The goal of the current study was to test the hypothesis that increased O2(˙-) scavenging alone or in combination with increased H2O2 scavenging (mtAO mice) enhances in vivo muscle insulin action in the HF-fed mouse. Insulin action was examined in conscious, unrestrained and unstressed wild type (WT), sod2(tg), mcat(tg) and mtAO mice using hyperinsulinemic-euglycemic clamps (insulin clamps) combined with radioactive glucose tracers following sixteen weeks of normal chow or HF (60% calories from fat) feeding. Glucose infusion rates, whole body glucose disappearance, and muscle glucose uptake during the insulin clamp were similar in chow- and HF-fed WT and sod2(tg) mice. Consistent with our previous work, HF-fed mcat(tg) mice had improved muscle insulin action, however, an additive effect was not seen in mtAO mice. Insulin-stimulated Akt phosphorylation in muscle from clamped mice was consistent with glucose flux measurements. These results demonstrate that increased O2(˙-) scavenging does not improve muscle insulin action in the HF-fed mouse alone or when coupled to increased H2O2 scavenging.

PMID:
25992608
PMCID:
PMC4437982
DOI:
10.1371/journal.pone.0126732
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center