Electroacupuncture improves diabetes-associated cognitive impairment in rats: potential involvement of hippocampal insulin receptor substrates 1/phosphatidylinositol 3-kinase/protein kinase B signaling pathway activation.

Abstract

Background: Cognitive impairment is highly prevalent in people with diabetes. Electroacupuncture improves diabetes-associated cognitive impairment (DACI), but its regulatory mechanism remains unclear.

Methods: The DACI model was established in rats via high-fat diet combined with low-dose intraperitoneal streptozocin. The acupuncture points Yishu (EX-B3), Zusanli (ST36), and Neiting (ST44) were chosen for electroacupuncture therapy. Cognitive function was assessed by Morris water maze test. Staining with hematoxylin and eosin was used to find the pathological changes in the hippocampus. The expression levels of relative proteins were analyzed by Western blot and immunofluorescence. In addition, ELISA was used to measure the levels of lactate and pyruvate in the hippocampus.

Results: Electroacupuncture can improve the learning and memory ability of DACI model rats (P<0.01) and hippocampal morphology; electroacupuncture can significantly increase the phosphorylated protein ratios of P-insulin receptor substrates 1 (P-IRS1)/IRS1, P-phosphoinositide 3-kinase (P-PI3K)/PI3K, and P-protein kinase B (P-AKT)/AKT (P < 0.001) and mean fluorescence intensity of P-IRS1, P-PI3K, and P-AKT (P < 0.01); electroacupuncture can promote the expression of glucose transporters (GLUTs) (P < 0.01) and monocarboxylic transporters (MCTs) (P < 0.01) and improves the contents of pyruvate and lactate in the hippocampus of DACI model rats (P < 0.01); Signaling pathway inhibitor LY294002 attenuated the above improvement (P < 0.05).

Conclusion: Electroacupuncture's mechanism may be involved in activating the IRS1/PI3K/AKT pathway, promoting the expression of GLUTs and MCTs, and regulating hippocampal energy metabolism.