RESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal cell injury and infla-mmation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats, the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear. AIM: To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats. METHODS: A T2DM rat model was induced via a high-glucose and high-fat diet, combined with a low-dose streptozotocin injection. T2DM rats were divided into DJB operation and Sham operation groups. DJB surgical intervention was carried out on T2DM rats. The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis. Proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry, quantitative real-time PCR, Western blotting, and immunofluorescence. RESULTS: Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery, compared to the T2DM-Sham groups of rats. Oxidative stress-related proteins (glucagon-like peptide 1 receptor, Nrf2, and HO-1) were significantly increased (P < 0.05) in the hypothalamus of rats with T2DM after DJB surgery. DJB surgery significantly reduced (P < 0.05) hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin (IL)-1ß and IL-6. DJB surgery significantly reduced (P < 0.05) the expression of factors related to neuronal injury (glial fibrillary acidic protein and Caspase-3) in the hypothalamus of T2DM rats and upregulated (P < 0.05) the expression of neuroprotective factors (C-fos, Ki67, Bcl-2, and BDNF), thereby reducing hypothalamic injury in T2DM rats. CONCLUSION: DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.
RESUMO
This study was set out to determine the association of serum adiponectin and oxidative stress in newly diagnosed type 2 diabetes patients. 106 patients with newly diagnosed type 2 diabetes were recruited. Simultaneously scanning of the extracranial carotid arteries, common iliac arteries and femoral arteries were performed for measurement of intima media thickness (IMT) in all subjects. Atherosclerotic plaque was defined as IMT value >1.3 mm. The serum levels of adiponectin and 8-iso-prostaglandin F2α (8-iso-PGF2α), a marker of oxidative stress, were examined by enzyme-linked immunosorbent assay. Metabolic parameters were detected by clinical chemistry. According to the results, all of 106 patients with type 2 diabetes were newly diagnosed within 12 months, and aged 60.68±4.32 years. The level of serum adiponectin in newly diagnosed type 2 diabetes patients was lower than that in healthy subjects. Furthermore, type 2 diabetes patients with atherosclerotic plaques had lower serum adiponectin level than those without atherosclerotic plaques. Serum 8-iso-PGF2α level in newly diagnosed type 2 diabetes patients was higher than that in healthy subjects. Further analyses showed that serum adiponectin level was reversely associated with serum 8-iso-PGF2α in newly diagnosed type 2 diabetes patients. Additionally, the atherosclerotic plaques in newly diagnosed type 2 diabetes patients were positively correlated with total cholesterol, but negatively correlated with serum adiponectin level. Taken together, this study suggests that in newly diagnosed type 2 diabetes, serum adiponectin levels are probably associated with oxidative stress and also with the severity of atherosclerosis.