[Mechanism of electroacupuncture regulating nuclear factor-κB pathway to improve the dedifferentiation of pancreatic β-cells in rats with T2DM]

Abstract

Objective: To observe the effects of electroacupuncture (EA) on the expression of serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the pancreatic nuclear factor-κB (NF-κB) pathway in type 2 diabetes mellitus (T2DM) rats, and to explore the possible mechanism by which EA improving the dedifferentiation of pancreatic β-cells in the treatment of T2DM.

Methods: Among 18 SPF-grade male Wistar rats, 6 rats were randomly selected as the control group, and the remaining 12 rats were fed with high-sugar and high-fat diet combined with intraperitoneal injection of 2% streptozotocin solution (35 mg/kg) to establish T2DM model. After successful modeling, the 12 rats were randomly divided into a model group and an EA group, with 6 rats in each group. The EA group received EA at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Weiwanxiashu" (EX-B 3), and "Pishu" (BL 20), with continuous wave, frequency of 15 Hz, current intensity of 2 mA, for 20 min each time, once a day, 6 times a week, for a total of 6 weeks. Fasting blood glucose (FBG) levels were measured before modeling and before and after intervention. After intervention, ELISA was used to detect the serum fasting insulin (FINS), IL-1β and TNF-α levels, and the β-cell function index (HOMA-β) and insulin resistance index (HOMA-IR) were calculated; HE staining was used to observe the morphology of the pancreatic islets; Western blot was used to detect the protein expression of pancreatic forkhead box protein O1 (FoxO1), pancreatic and duodenal homeobox 1 (PDX-1), neurogenin 3 (NGN3), and NF-κB p65.

Results: After intervention, the FBG in the model group was higher than that in the control group (P<0.01), and the FBG in the EA group was lower than that in the model group (P<0.01). Compared with the control group, the model group had increased levels of serum FINS, IL-1β, TNF-α, and HOMA-IR (P<0.01), and decreased HOMA-β (P<0.01), reduced protein expression of pancreatic FoxO1 and PDX-1 (P<0.01), and increased protein expression of pancreatic NGN3 and NF-κB p65 (P<0.01, P<0.05). Compared with the model group, the EA group had lower serum FINS, IL-1β, TNF-α levels, and HOMA-IR (P<0.01), higher HOMA-β (P<0.05), increased protein expression of pancreatic FoxO1 and PDX-1 (P<0.01, P<0.05), and decreased protein expression of pancreatic NGN3 and NF-κB p65 (P<0.01, P<0.05). The control group's pancreatic islets showed no obvious abnormalities; the model group's pancreatic islets were irregular in shape and had unclear boundaries with the surrounding area, with immune cell infiltration, reduced β-cell nuclei, disordered arrangement of islet cells, and increased intercellular spaces; the EA group showed improvements in islet morphology, immune cell infiltration, β-cell nuclei count, and the arrangement and spacing of islet cells approaching normal.

Conclusion: EA could lower the blood glucose levels in T2DM rats, alleviate chronic inflammatory responses in the islets, and improve the dedifferentiation of pancreatic β-cells, which may be related to the inhibition of pancreatic NF-κB pathway expression.

Keywords: chronic inflammatory response in islets; dedifferentiation of pancreatic β-cells; electroacupuncture; nuclear factor-κB pathway; type 2 diabetes mellitus (T2DM).