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Diabetes‐induced hyperglycemia is associated with inhibition of insulin pathway without NF‐κB‐p65 activation in skeletal muscle.
Author(s) -
Kelleher Andrew Ryan,
Fairchild Timothy,
Keslacy Stefan
Publication year - 2009
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.23.1_supplement.990.27
Subject(s) - medicine , endocrinology , inflammation , insulin , adipose tissue , skeletal muscle , diabetes mellitus , insulin receptor , streptozotocin , chemistry , iκb kinase , insulin resistance , phosphorylation , nf κb , biochemistry
Obesity‐induced inflammation is associated with the onset of diabetes. Whether obesity‐related increase in adipose tissue or hyperglycemia is the initiator of this inflammation is still unknown. Nuclear‐Factor kB (NF‐κB) is a critical transcription factor in the inflammatory process but its role in diabetes onset is unclear. We hypothesized that hyperglycemia is an early modulator of key proteins in the NF‐κB cascade. 10 Streptozotocin‐(STZ)‐treated rats were compared to10 control rats. Using total, cytosolic and nuclear protein extracts from hindlimb muscles: soleus (SOL), extensor digitorum longus (EDL), gastrocnemius (GM), and liver tissue, we assessed key proteins of NF‐κB and insulin pathway. STZ treatment decreased insulin to 3.9 ± 1.2 μU/ml and induced a concomitant hyperglycemia (296.5 ± 15.6mg/dL). SOL, EDL and GM mass decreased and liver mass increased in STZ‐treated animals. p65 expression in GM, and liver increased in diabetic rats, however, there was no IκB degradation or IKK phosphorylation. Muscle p65 remained bound to IκB and did not translocate or bind to DNA. Although insulin receptor (IR) and substrate‐1 (IRS‐1) expression were similar, STZ treatment abrogated their phosphorylation. Despite upstream inactivation of insulin pathway, STZ treatment did not acutely activate the NF‐κB cascade. Therefore, it is unlikely that hyperglycemia initiates obesity‐induced inflammation.