Published online Feb 15, 2024. doi: 10.4239/wjd.v15.i2.287
Peer-review started: October 10, 2023
First decision: November 17, 2023
Revised: December 12, 2023
Accepted: January 12, 2024
Article in press: January 12, 2024
Published online: February 15, 2024
Processing time: 117 Days and 2.4 Hours
Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal injury and inflammation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats, but its role in brain injury and the underlying mechanisms are still unclear.
DJB can increase serum glucagon-like peptide 1 (GLP-1) Levels and enhance brain glucose utilization, playing a positive role in the treatment of diabetes. Therefore, GLP-1 signaling may play a significant role after DJB surgery in alleviating T2DM-related brain injury.
To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats.
A T2DM rat model was induced via a high-glucose, high-fat diet, and a low-dose streptozotocin injection. T2DM rats underwent DJB surgery or Sham surgery. Differential expression of hypothalamic proteins and genes was analyzed by protein microarray, flow cytometry, quantitative real-time PCR, western blot, and immunofluorescence.
Protein microarray results showed significant differences between the T2DM-Sham rats and the T2DM-DJB rats in signaling proteins related to oxidative stress, inflammation, and neuronal injury. DJB surgery increased the serum levels of GLP-1 and upregulated the expression of GLP-1 receptor and antioxidant signaling proteins (Nrf2 and HO-1) in the hypothalamic tissue of T2DM rats. DJB also reduced the expression of hypothalamic inflammatory and nerve cell injury-related factors, playing a neuroprotective role and reducing hypothalamic injury.
DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the GLP-1-mediated Nrf2/HO-1 signaling pathway.
Further investigation is needed to determine the influence of enteric neural or endocrine pathways after DJB surgery on the amelioration of diabetes-induced central brain injury by GLP-1.