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The lipid peroxidation end‐product and oxidant 4‐ hydroxynonenal causes insulin resistance in rat slow‐twitch skeletal muscle in vitro
Author(s) -
Henriksen Erik John,
Prasannarong Mujalin,
Santos Fernando Reyes,
Giovannini Franchesca Jo
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.701.3
Subject(s) - medicine , 4 hydroxynonenal , skeletal muscle , insulin resistance , endocrinology , lipid peroxidation , chemistry , phosphorylation , protein kinase b , insulin , glucose uptake , lipid oxidation , glucose transporter , oxidative phosphorylation , insulin receptor , oxidative stress , biochemistry , antioxidant , biology
The impact of the lipid peroxidation end‐product, reactive aldehyde, and oxidant 4‐hydroxynonenal (4‐HNE) on the glucose transport system in rat slow‐twitch skeletal muscle is currently unknown. Therefore, we assessed the effect of 4‐HNE on insulin signaling (IRS proteins and phosphorylation of Akt Ser473 (pAkt) and AS160 Thr642 (pAS160)) and glucose transport in slow‐twitch muscle. Soleus strips from lean Zucker rats were incubated with 4‐ HNE (50 μM) for up to 6 hr. Insulin‐stimulated (5 mU/ml) glucose transport was decreased by 4‐HNE at 2 hr (30%), 4 hr (26%), and 6 hr (39%) (p<0.05). At 2 hr of 4‐HNE treatment with insulin, pAS160 was decreased by 28%, whereas pAkt was only reduced by 11% and IRS‐1 protein was not changed. At 4 hr, pAS160 and pAkt were decreased by 22% and IRS‐1 was 39% lower. At 6 hr, pAS160 was 47% lower, pAkt was decreased by 26%, and IRS‐1 protein was reduced by 51%. Interestingly, IRS‐2 was slightly decreased (17%) only at 6 hr. These data indicate that the lipid peroxidation end‐product and oxidant 4‐HNE induces insulin resistance of glucose transport activity in rat slow‐twitch skeletal muscle, associated initially with impaired AS160 phosphorylation and subsequently with impaired Akt phosphorylation and selective loss of IRS‐1 protein. These results provide further support for an important role of lipid‐derived oxidative stress in the etiology of skeletal muscle insulin resistance.