期刊
ACTA DIABETOLOGICA
卷 47, 期 4, 页码 315-323出版社
SPRINGER-VERLAG ITALIA SRL
DOI: 10.1007/s00592-010-0209-1
关键词
STZ; p65; NF-kappa B; Insulin; Skeletal muscle
资金
- Syracuse University
Type 1 diabetes mellitus (DM)-induced skeletal muscle atrophy is associated with an increased incidence in morbidity and mortality. Although the precise mechanism of diabetes-induced skeletal muscle atrophy remains to be established, several NF-kappa B-dependent pro-inflammatory genes have been identified as potential therapeutic targets. Moreover, activation of NF-kappa B has previously been shown to be required for cytokine-induced loss of skeletal muscle proteins. Therefore, we investigated activation of the NF-kappa B canonical pathway, concomitant to insulin signaling activation in skeletal muscle from diabetes-induced rats. Ten rats injected with streptozotocin (STZ) 4 weeks prior to tissue extraction were compared to 10 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 important for the activation of both NF-kappa B and insulin pathways. Insulin blood concentration decreased to 3.9 +/- A 1.2 mU/ml following STZ-injection resulting in hyperglycemia (17.9 +/- A 0.7 mmol/l). SOL, EDL and GM mass decreased, and liver mass increased following STZ injection. NF-kappa B/p65 content in SOL, GM and liver increased in STZ-injected rats, without any change in I kappa B degradation or IKK phosphorylation. Muscle NF-kappa B/p65 remained bound to I kappa B and did not translocate or bind to DNA. Although the canonical NF-kappa B cascade was not activated, STZ induced a decrease in insulin pathway proteins including insulin receptor (IR) and substrate (IRS-1) content and phosphorylation compared to control animals. A downregulation of insulin pathway proteins and muscle atrophy occurred in response to STZ administration, and despite increased p65 content, STZ treatment did not activate the canonical NF-kappa B cascade. Therefore, it is unlikely that hyperglycemia initiates skeletal muscle atrophy via activation of the NF-kappa B canonical pathway.
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