Objective: To observe the effect of anti-diabetic drug glucagon-like peptide-1 (GLP-1) on 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). High-fat and high-sugar diet combined with streptozotocin (STZ) is used to induce type 2 diabetes models. The diabetic rat models were randomly divided into diabetic group and GLP-1 group, and the non-treated diabetic group. After 25 days, rats in the GLP-1 group were provided with GLP-1 and diabetes formation through a subcutaneous sustained-release pump. (30 pmol/kg/min) 7 days treatment. After treatment, the Morris water maze test was used to evaluate the learning and cognitive abilities of each group of rats, and the hippocampus tissue of the rat brain was obtained to detect the transcription of cognitive-related genes in real time. PCR (real-time PCR) and Western blotting detect the expression of cognitive-related proteins, and immunohistochemistry detects the expression and intracellular localization of cognitive-related proteins.
Result: Morris water maze experiment showed that the learning and memory function of diabetic rats was significantly reduced (P\u003c0.05). Fluorescence quantitative PCR results showed APP, BACE1, Arc, ERK1/2, PKA and PKC in the brain. The gene transcription of diabetic rats is increased (P\u003c0.05). Western Blotting and immunohistochemistry results show that the expression of Arc protein molecules in diabetic rats is 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). The expression of APP, BACE1, Arc, ERK1/2, PKA and PKC genes in the brain was significantly (P\u003c0.05), and the arc expression decreased.
Conclusion: GLP-1 treatment can significantly improve the learning and memory dysfunction of type 2 diabetic rats. This effect can be achieved by regulating the PKC, PKA, ERK1/2 pathways of the cell and inhibiting the expression of Arc.