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[Glucagon-like peptide 1 improves learning and memory abilities of rats with type 2 diabetes]
Zhao-Guang Tan1, Wei-Hong Gao, Xiang-Sheng Cai
11School of Biotechnology, 2International Center for Metabolic Diseases,4Department of Neurobiology,School of Basic Medical Sciences,Southern Medical University,Guangzhou 510515,China; 3Dongguan SMU Metabolic Medicine R&D Inc,Dongguan 523000,China; 5UCLA Center for Excellence in Pancreatic Disease,David Geffen School of Medicine,University of California,Los Angeles,California 90095,USA.
Objective:
To investigate the effect of glucagon-like peptide 1 (GLP-1) on cognitive dysfunction in diabetic rats.
Methods:
Male SD rats were randomly divided into normal control group, diabetes mellitus (DM) group, and GLP-1 treatment group. Rat models of type 2 diabetes were established by high-sugar and high-fat feeding and streptozotocin (STZ) injection, and 25 days after the onset of diabetes, GLP-1 was infused in GLP-1 treatment group at the rate of 30 pmol·kg-1·min-1 via a subcutaneous osmotic pump for 7 days. The learning and cognitive ability of the rats was assessed with Morris water maze test, and the expression of cognition-related genes in the hippocampus tissue was detected with real-time PCR, Western blotting and immunohistochemical staining.
Results:
Compared with the normal control group, the diabetic rats showed significantly decreased learning and memory abilities (P<0.05) with increased hippocampal expressions of APP, BACE1, Arc, ERK1/2, PKA, and PKC mRNAs (P<0.05) and Arc protein. Compared with diabetic rats, GLP-1-treated rats showed significantly improvements in the learning and memory function (P<0.05) with decreased expressions of APP, BACE1, Arc, ERK1/2, and PKA mRNAs (P<0.05) and Arc protein.
Conclusion:
GLP-1 can improve cognitive dysfunctions in diabetic rats possibly by regulating the PKC, PKA, and ERK1/2 pathways and inhibiting Arc expression in the hippocampus.
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