title: Enhanced mitochondrial superoxide scavenging does not improve muscle insulin action in the high fat-fed mouse.
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.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Lark
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Kang
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Lustig
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Bonner
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Freyja D
authors.initials: FD
authors.lastname: James
authors.affiliation: 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.
authors.forename: P Darrell
authors.initials: PD
authors.lastname: Neufer
authors.affiliation: 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.
authors.forename: David H
authors.initials: DH
authors.lastname: Wasserman
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*
chemical_list: D007328:Insulin; D013481:Superoxides