Long-Lasting Exendin-4 Fusion Protein Improves Memory Deficits in High-Fat Diet/Streptozotocin-Induced Diabetic Mice
Glucagon-like peptide 1 (GLP-1) mimetics have been approved as an adjunct therapy for glycemic control in type 2 diabetic patients for the increased insulin secretion under hyperglycemic conditions. Recently, it is reported that such agents elicit neuroprotective effects against diabetes-associated...
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MDPI AG
2020-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/2/159 |
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| author | Kyung-Ah Park Zhen Jin Jong Youl Lee Hyeong Seok An Eun Bee Choi Kyung Eun Kim Hyun Joo Shin Eun Ae Jeong Kyoung Ah Min Meong Cheol Shin Gu Seob Roh |
| author_facet | Kyung-Ah Park Zhen Jin Jong Youl Lee Hyeong Seok An Eun Bee Choi Kyung Eun Kim Hyun Joo Shin Eun Ae Jeong Kyoung Ah Min Meong Cheol Shin Gu Seob Roh |
| author_sort | Kyung-Ah Park |
| collection | DOAJ |
| description | Glucagon-like peptide 1 (GLP-1) mimetics have been approved as an adjunct therapy for glycemic control in type 2 diabetic patients for the increased insulin secretion under hyperglycemic conditions. Recently, it is reported that such agents elicit neuroprotective effects against diabetes-associated cognitive decline. However, there is an issue of poor compliance by multiple daily subcutaneous injections for sufficient glycemic control due to their short duration, and neuroprotective actions were not fully studied, yet. In this study, using the prepared exendin-4 fusion protein agent, we investigated the pharmacokinetic profile and the role of this GLP-1 mimetics on memory deficits in a high-fat diet (HFD)/streptozotocin (STZ) mouse model of type 2 diabetic mellitus. After induction of diabetes, mice were administered weekly by intraperitoneal injection of GLP-1 mimetics for 6 weeks. This treatment reversed HFD/STZ-induced metabolic symptoms of increased body weight, hyperglycemia, and hepatic steatosis. Furthermore, the impaired cognitive performance of diabetic mice was significantly reversed by GLP-1 mimetics. GLP-1 mimetic treatment also reversed decreases in GLP-1/GLP-1 receptor expression levels in both the pancreas and hippocampus of diabetic mice; increases in hippocampal inflammation, mitochondrial fission, and calcium-binding protein levels were also reversed. These findings suggest that GLP-1 mimetics are promising agents for both diabetes and neurodegenerative diseases that are associated with increased GLP-1 expression in the brain. |
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| format | Article |
| id | doaj.art-f383438c73fb4a749a8ae4e91b99996b |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T12:14:29Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-f383438c73fb4a749a8ae4e91b99996b2022-12-22T04:24:27ZengMDPI AGPharmaceutics1999-49232020-02-0112215910.3390/pharmaceutics12020159pharmaceutics12020159Long-Lasting Exendin-4 Fusion Protein Improves Memory Deficits in High-Fat Diet/Streptozotocin-Induced Diabetic MiceKyung-Ah Park0Zhen Jin1Jong Youl Lee2Hyeong Seok An3Eun Bee Choi4Kyung Eun Kim5Hyun Joo Shin6Eun Ae Jeong7Kyoung Ah Min8Meong Cheol Shin9Gu Seob Roh10Department of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, KoreaCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gimhae, Gyeongnam 50834, KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Gyeongnam 52828, KoreaDepartment of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju, Gyeongnam 52727, KoreaGlucagon-like peptide 1 (GLP-1) mimetics have been approved as an adjunct therapy for glycemic control in type 2 diabetic patients for the increased insulin secretion under hyperglycemic conditions. Recently, it is reported that such agents elicit neuroprotective effects against diabetes-associated cognitive decline. However, there is an issue of poor compliance by multiple daily subcutaneous injections for sufficient glycemic control due to their short duration, and neuroprotective actions were not fully studied, yet. In this study, using the prepared exendin-4 fusion protein agent, we investigated the pharmacokinetic profile and the role of this GLP-1 mimetics on memory deficits in a high-fat diet (HFD)/streptozotocin (STZ) mouse model of type 2 diabetic mellitus. After induction of diabetes, mice were administered weekly by intraperitoneal injection of GLP-1 mimetics for 6 weeks. This treatment reversed HFD/STZ-induced metabolic symptoms of increased body weight, hyperglycemia, and hepatic steatosis. Furthermore, the impaired cognitive performance of diabetic mice was significantly reversed by GLP-1 mimetics. GLP-1 mimetic treatment also reversed decreases in GLP-1/GLP-1 receptor expression levels in both the pancreas and hippocampus of diabetic mice; increases in hippocampal inflammation, mitochondrial fission, and calcium-binding protein levels were also reversed. These findings suggest that GLP-1 mimetics are promising agents for both diabetes and neurodegenerative diseases that are associated with increased GLP-1 expression in the brain.https://www.mdpi.com/1999-4923/12/2/159exendin-4fusion proteinglucagon-like peptide 1r (glp-1r)memory deficitshippocampusdiabetic mice |
| spellingShingle | Kyung-Ah Park Zhen Jin Jong Youl Lee Hyeong Seok An Eun Bee Choi Kyung Eun Kim Hyun Joo Shin Eun Ae Jeong Kyoung Ah Min Meong Cheol Shin Gu Seob Roh Long-Lasting Exendin-4 Fusion Protein Improves Memory Deficits in High-Fat Diet/Streptozotocin-Induced Diabetic Mice Pharmaceutics exendin-4 fusion protein glucagon-like peptide 1r (glp-1r) memory deficits hippocampus diabetic mice |
| title | Long-Lasting Exendin-4 Fusion Protein Improves Memory Deficits in High-Fat Diet/Streptozotocin-Induced Diabetic Mice |
| title_full | Long-Lasting Exendin-4 Fusion Protein Improves Memory Deficits in High-Fat Diet/Streptozotocin-Induced Diabetic Mice |
| title_fullStr | Long-Lasting Exendin-4 Fusion Protein Improves Memory Deficits in High-Fat Diet/Streptozotocin-Induced Diabetic Mice |
| title_full_unstemmed | Long-Lasting Exendin-4 Fusion Protein Improves Memory Deficits in High-Fat Diet/Streptozotocin-Induced Diabetic Mice |
| title_short | Long-Lasting Exendin-4 Fusion Protein Improves Memory Deficits in High-Fat Diet/Streptozotocin-Induced Diabetic Mice |
| title_sort | long lasting exendin 4 fusion protein improves memory deficits in high fat diet streptozotocin induced diabetic mice |
| topic | exendin-4 fusion protein glucagon-like peptide 1r (glp-1r) memory deficits hippocampus diabetic mice |
| url | https://www.mdpi.com/1999-4923/12/2/159 |
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