TFP5, a Peptide Derived from Cdk5 Activator p35, Protects Pancreatic β Cells from Glucose Toxicity
© 2023. Springer Science+Business Media, LLC, part of Springer Nature..
We studied the effect of TFP5 on MIN6 cells (cultured mouse islet β cells) treated with different concentrations of glucose (5 or 25 mM). The results were verified in C57BL/6J mice (control; n=12) and db/db mice with type 2 diabetes mellitus (n=12). To synthesize TFP5, peptide p5 (a derivative of p35 protein, activator of cyclin-dependent kinase 5, Cdk5) was conjugated with a FITC tag at the N-terminus and an 11-amino acid TAT protein transduction domain at the C-terminus. TFP5 was employed to inhibit Cdk5 activity and then to evaluate its efficiency in treating experimental type 2 diabetes mellitus. TFP5 effectively inhibited the pathological hyperactivity of Cdk5, enhanced insulin secretion, and protected pancreatic β cells from apoptosis in vitro and in vivo. In addition, TFP5 inhibited inflammation in pancreatic islets by reducing the expression of inflammatory cytokines TGF-β1, TNFα, and IL-1β. These novel data indicates that TFP5 is a promising candidate for treatment of type 2 diabetes mellitus.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:176 |
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| Enthalten in: |
Bulletin of experimental biology and medicine - 176(2023), 1 vom: 29. Nov., Seite 19-25 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, S-Y [VerfasserIn] |
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| Links: |
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| Themen: |
Apoptosis |
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| Anmerkungen: |
Date Completed 19.12.2023 Date Revised 02.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s10517-023-05959-z |
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| 520 | |a We studied the effect of TFP5 on MIN6 cells (cultured mouse islet β cells) treated with different concentrations of glucose (5 or 25 mM). The results were verified in C57BL/6J mice (control; n=12) and db/db mice with type 2 diabetes mellitus (n=12). To synthesize TFP5, peptide p5 (a derivative of p35 protein, activator of cyclin-dependent kinase 5, Cdk5) was conjugated with a FITC tag at the N-terminus and an 11-amino acid TAT protein transduction domain at the C-terminus. TFP5 was employed to inhibit Cdk5 activity and then to evaluate its efficiency in treating experimental type 2 diabetes mellitus. TFP5 effectively inhibited the pathological hyperactivity of Cdk5, enhanced insulin secretion, and protected pancreatic β cells from apoptosis in vitro and in vivo. In addition, TFP5 inhibited inflammation in pancreatic islets by reducing the expression of inflammatory cytokines TGF-β1, TNFα, and IL-1β. These novel data indicates that TFP5 is a promising candidate for treatment of type 2 diabetes mellitus | ||
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| 700 | 1 | |a Bao, X |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Y-L |e verfasserin |4 aut | |
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