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Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats.
Guo, Xiying; Lei, Min; Zhao, Jiangyan; Wu, Min; Ren, Zhanhong; Yang, Xiaosong; Ouyang, Changhan; Liu, Xiufen; Liu, Chao; Chen, Qingjie.
Afiliación
  • Guo X; Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, China.
  • Lei M; Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, China.
  • Zhao J; Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, China.
  • Wu M; Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, China.
  • Ren Z; Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, China.
  • Yang X; Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, China.
  • Ouyang C; Pharmacy College, Xianning Medical College, Hubei University of Science and Technology, Xianning, China.
  • Liu X; Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, China.
  • Liu C; Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, China.
  • Chen Q; Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, China.
Front Pharmacol ; 14: 1146960, 2023.
Article en En | MEDLINE | ID: mdl-37701028
ABSTRACT

Background:

One of the typical symptoms of diabetes mellitus patients was memory impairment, which was followed by gradual cognitive deterioration and for which there is no efficient treatment. The anti-diabetic incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were demonstrated to have highly neuroprotective benefits in animal models of AD. We wanted to find out how the GLP-1/GIP dual agonist tirzepatide affected diabetes's impairment of spatial learning memory.

Methods:

High fat diet and streptozotocin injection-induced diabetic rats were injected intraperitoneally with Tirzepatide (1.35 mg/kg) once a week. The protective effects were assessed using the Morris water maze test, immunofluorescence, and Western blot analysis. Golgi staining was adopted for quantified dendritic spines.

Results:

Tirzepatide significantly improved impaired glucose tolerance, fasting blood glucose level, and insulin level in diabetic rats. Then, tirzepatide dramatically alleviated spatial learning and memory impairment, inhibited Aß accumulation, prevented structural damage, boosted the synthesis of synaptic proteins and increased dendritic spines formation in diabetic hippocampus. Furthermore, some aberrant changes in signal molecules concerning inflammation signaling pathways were normalized after tirzepatide treatment in diabetic rats. Finally, PI3K/Akt/GSK3ß signaling pathway was restored by tirzepatide.

Conclusion:

Tirzepatide obviously exerts a protective effect against spatial learning and memory impairment, potentially through regulating abnormal insulin resistance and inflammatory responses.
Palabras clave

Texto completo: 1 Banco de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2023 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Banco de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2023 Tipo del documento: Article País de afiliación: China