Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats
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 p...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1146960/full |
| _version_ | 1797736174710685696 |
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| author | Xiying Guo Min Lei Jiangyan Zhao Min Wu Zhanhong Ren Xiaosong Yang Changhan Ouyang Xiufen Liu Chao Liu Qingjie Chen |
| author_facet | Xiying Guo Min Lei Jiangyan Zhao Min Wu Zhanhong Ren Xiaosong Yang Changhan Ouyang Xiufen Liu Chao Liu Qingjie Chen |
| author_sort | Xiying Guo |
| collection | DOAJ |
| description | 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 Aβ 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/GSK3β 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. |
| first_indexed | 2024-03-12T13:08:50Z |
| format | Article |
| id | doaj.art-e3497a9a50f949fd9b3ecb1e3f5736fe |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-12T13:08:50Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e3497a9a50f949fd9b3ecb1e3f5736fe2023-08-28T08:36:18ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-08-011410.3389/fphar.2023.11469601146960Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic ratsXiying Guo0Min Lei1Jiangyan Zhao2Min Wu3Zhanhong Ren4Xiaosong Yang5Changhan Ouyang6Xiufen Liu7Chao Liu8Qingjie Chen9Hubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, ChinaHubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, ChinaHubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, ChinaHubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, ChinaHubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, ChinaHubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, ChinaPharmacy College, Xianning Medical College, Hubei University of Science and Technology, Xianning, ChinaHubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, ChinaHubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, ChinaHubei Key Laboratory of Diabetes and Angiopathy, Xianning Medical College, Medical Research Institute, Hubei University of Science and Technology, Xianning, ChinaBackground: 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 Aβ 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/GSK3β 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.https://www.frontiersin.org/articles/10.3389/fphar.2023.1146960/fulltirzepatidediabetes mellitusspatial learning and memoryAβsynaptic plasticityinflammation |
| spellingShingle | Xiying Guo Min Lei Jiangyan Zhao Min Wu Zhanhong Ren Xiaosong Yang Changhan Ouyang Xiufen Liu Chao Liu Qingjie Chen Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats Frontiers in Pharmacology tirzepatide diabetes mellitus spatial learning and memory Aβ synaptic plasticity inflammation |
| title | Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats |
| title_full | Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats |
| title_fullStr | Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats |
| title_full_unstemmed | Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats |
| title_short | Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats |
| title_sort | tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats |
| topic | tirzepatide diabetes mellitus spatial learning and memory Aβ synaptic plasticity inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1146960/full |
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