TY - JOUR
T1 - Does skeletal muscle oxidative stress initiate insulin resistance in genetically predisposed individuals?
AU - Samocha-Bonet, Dorit
AU - Heilbronn, Leonie K.
AU - Lichtenberg, Dov
AU - Campbell, Lesley V.
N1 - Funding Information:
Research in the laboratories of D.S.B., L.K.H. and L.V.C. is funded by the National Health and Medical Council of Australia (NHMRC) and the Diabetes Australia Research Trust (DART). Research in the laboratory of D.L. is supported by the Lady Davis Chair of Biochemistry. We would like to thank Nigel Turner for his critical comments on this manuscript.
PY - 2010/2
Y1 - 2010/2
N2 - Reactive oxygen species (ROS) are postulated to be a common trigger of insulin resistance. For example, treatment of adipocytes with either tumor-necrosis factor-α or dexamethasone increases ROS before impairing glucose uptake. Similarly, treatment with mitochondria-specific antioxidants preserves insulin sensitivity in animal models of insulin resistance. However, it remains unclear whether ROS contribute to insulin resistance in humans. First-degree relatives (FDRs) of type 2 diabetes subjects are at increased risk of developing insulin resistance and type 2 diabetes. Here we review the documented metabolic impairments in FDRs that could contribute to insulin resistance via increased oxidative stress. We propose that lipotoxic intermediates and lipid peroxides in skeletal muscle interfere with insulin signaling and might cause insulin resistance in these 'at risk' individuals.
AB - Reactive oxygen species (ROS) are postulated to be a common trigger of insulin resistance. For example, treatment of adipocytes with either tumor-necrosis factor-α or dexamethasone increases ROS before impairing glucose uptake. Similarly, treatment with mitochondria-specific antioxidants preserves insulin sensitivity in animal models of insulin resistance. However, it remains unclear whether ROS contribute to insulin resistance in humans. First-degree relatives (FDRs) of type 2 diabetes subjects are at increased risk of developing insulin resistance and type 2 diabetes. Here we review the documented metabolic impairments in FDRs that could contribute to insulin resistance via increased oxidative stress. We propose that lipotoxic intermediates and lipid peroxides in skeletal muscle interfere with insulin signaling and might cause insulin resistance in these 'at risk' individuals.
UR - http://www.scopus.com/inward/record.url?scp=75249106467&partnerID=8YFLogxK
U2 - 10.1016/j.tem.2009.09.008
DO - 10.1016/j.tem.2009.09.008
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C2 - 19854062
AN - SCOPUS:75249106467
SN - 1043-2760
VL - 21
SP - 83
EP - 88
JO - Trends in Endocrinology and Metabolism
JF - Trends in Endocrinology and Metabolism
IS - 2
ER -