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摘要
Patients who experience acute ischemic stroke may develop hyperglycemia, even in the absence of diabetes. In the current study we determined the effects of acute stroke on hepatic insulin signaling, TNF-alpha expression, endoplasmic reticulum (ER) stress, the activities of c-Jun N-terminal kinase (JNK), inhibitor kappa B kinase beta (IKK-beta), and nuclear factor-kappa B (NF-kappa B) pathways. Rats with cerebral ischemia developed higher blood glucose, and insulin levels, and insulin resistance index, as well as hepatic gluconeogenic enzyme expression compared with the sham-treated group. The hepatic TNF-alpha mRNA and protein levels were elevated in stroke rats in association with increased ER stress, phosphorylation of JNK1/2 and IKK-beta proteins, I kappa B/NF-kappa B signaling, and phosphorylation of insulin receptor-1 (IRS-1) at serine residue. The basal and insulin-stimulated tyrosine phosphorylation of IRS-1 and AKT proteins was reduced. In addition, acute stroke increased circulating catecholamines in association with hepatic adrenergic signaling activation. After administration of a nonselective beta-adrenergic receptor blocker (propranolol) before induction of cerebral ischemic injury, hepatic adrenergic transduction, TNF-alpha expression, ER stress, and the activation of the JNK1/2, IKK-beta, and NF-kappa B pathways, and serine phosphorylation of IRS-1 were all attenuated. In contrast, the phosphorylated IRS-1 at tyrosine site and AKT levels were partially restored with improved poststroke hyperglycemia and insulin resistance index. These results suggest that acute ischemic stroke can activate proinflammatory pathways in the liver by the catecholamines and is associated with the development of hepatic insulin resistance.
- 出版日期2014-4
