Objective: To observe the effect of anti-diabetic drug glucagon-like peptide-1 (GLP-1) on improving the learning and memory function of diabetic rats.
Method: Male SD rats were randomly divided into normal group (normal), diabetes model group (DM) and GLP-1 treatment group (GLP-1). The combination of a high-fat, high-sugar diet and streptozotocin (STZ) can induce type 2 diabetes models. Diabetic rat models were randomly divided into diabetes group and GLP-1 group. The rats in the diabetes group were untreated. At 25 days after the onset of diabetes, rats in the GLP-1 group received GLP-1 (30 pmol/kg/min) for 7 days through a sustained-release pump implanted subcutaneously. After treatment, the Morris water maze test was used to evaluate the learning and cognitive abilities of each group of rats to obtain rat brain hippocampus tissue. Real-time fluorescent quantitative PCR is used to detect transcription and western blotting of cognitive-related genes. This method (Westernblotting) detects the expression of cognitive-related proteins, and immunohistochemistry detects the expression and cell location of cognitive-related proteins.
Result: In the Morris water maze experiment, the learning and memory functions of diabetic rats were significantly reduced (P\u003c0.05). Gene transcription increased (P\u003c0.05), Western blot and immunohistochemistry results showed that the expression of Arc protein molecules in diabetic rats increased. Compared with the diabetes group, the learning and memory function of rats in the GLP-1 treatment group was significantly improved (P\u003c0.05), and the expression of APP, BACE1, Arc, ERK1/2, PKA and PKC genes in the brain was significantly reduced (P\u003c0.05), and the arc indicates reduction.
Conclusion: GLP-1 treatment may significantly improve the learning and memory impairment in type 2 diabetic rats. This effect can be achieved by regulating the PKC, PKA and ERK1/2 pathways of the cell and inhibiting the expression of Arc.