Lack of inducible nitric oxide synthase does not prevent aging-associated insulin resistance.
Inducible nitric oxide synthase (iNOS) is involved in obesity-induced insulin resistance. Since aging is accompanied by increased iNOS expression, the effect of iNOS gene deletion on aging-associated insulin resistance was investigated in 7-month-old (adult) and 22-month-old (old) iNOS knockout and wild-type mice using the hyperinsulinemic-euglycemic clamp. While body weight and fat mass were increased, muscle mass was reduced with aging in wild-type mice. However, body composition was not changed with aging in iNOS knockout mice due to increased locomotor activity. NO metabolites in plasma, and protein levels of iNOS and nitrotyrosine in skeletal muscle increased with aging in wild-type mice. Deletion of iNOS gene attenuated NO metabolites and nitrotyrosine with aging in iNOS knockout mice. Glucose uptake in whole body and skeletal muscle was reduced with aging in both wild-type and iNOS knockout mice and there was no difference between two groups. Plasma level of tumor necrosis factor-alpha and gene expression of proinflammatory cytokines in peripheral tissues were increased with aging in both groups, and that was more heightened in iNOS knockout mice. These results suggest that lack of iNOS does not prevent aging-associated insulin resistance in mice and heightened production of proinflammatory cytokines may be involved.
Cha
Hye-Na
HN
Department of Physiology, College of Medicine, Yeungnam University, Daegu, South Korea.
Kim
Yong-Woon
YW
Kim
Jong-Yeon
JY
Kim
Yong-Dae
YD
Song
In Hwan
IH
Min
Ki-Nam
KN
Park
So-Young
SY
D000273:Adipose Tissue / Q000033:anatomy & histology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D016207:Cytokines / Q000235:genetics; D017353:Gene Deletion; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism; D007249:Inflammation / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency* / Q000235:genetics; D010101:Oxygen Consumption; D016133:Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II