title: Lack of inducible nitric oxide synthase prevents lipid-induced skeletal muscle insulin resistance without attenuating cytokine level.
abstract: We examined whether deletion of inducible nitric oxide synthase (iNOS) could prevent lipid infusion-induced insulin resistance in iNOS-knockout and wild-type mice with the in vivo euglycemic-hyperinsulinemic clamp technique. Plasma NO metabolites were increased in lipid-infused wild-type mice, while they were not increased in iNOS-knockout mice. Plasma tumor necrosis factor-α levels were increased in both wild-type and iNOS-knockout by lipid-infusion. Lipid infusion reduced glucose infusion rate (GIR) and whole body glucose uptake in wild-type mice, whereas iNOS-knockout mice displayed comparable GIR and whole body glucose uptake compared with the control. In the gastrocnemius, lipid infusion decreased glucose uptake and glycolysis that were accompanied with increased phosphorylation of c-Jun N-terminal kinase and reduced phosphorylation of phosphoinositide 3-kinases and serine/threonine kinase Akt. However, lipid infusion did not affect glucose uptake or phosphorylation of these proteins in iNOS-knockout mice. The mRNA levels of inflammatory cytokines were also increased in the gastrocnemis of wild-type and iNOS-knockout mice by lipid infusion. Nitrotyrosine level in the gastrocnemius was increased in lipid-infused wild-type mice but it was not increased in iNOS-knockout mice. These results suggest that lack of iNOS prevents lipid infusion-induced skeletal muscle insulin resistance without attenuating cytokine levels.
authors: Department of Physiology, College of Medicine, Yeungnam University, South Korea.
authors: Hye-Na
authors: HN
authors: Cha
authors: Seung Eun
authors: SE
authors: Song
authors: Yong-Woon
authors: YW
authors: Kim
authors: Jong-Yeon
authors: JY
authors: Kim
authors: Kyu-Chang
authors: KC
authors: Won
authors: So-Young
authors: SY
authors: Park
mesh_terms: D000818:Animals; D004655:Emulsions / Q000494:pharmacology; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007333:Insulin Resistance; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency* / Q000235:genetics; D010743:Phospholipids / Q000494:pharmacology*; D013024:Soybean Oil / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D053583:Interleukin-1beta; D015850:Interleukin-6; D010743:Phospholipids; D014409:Tumor Necrosis Factor-alpha; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil; D006003:Glycogen; D052247:Nitric Oxide Synthase Type II; D005947:Glucose