Reduction of cardiac and renal dysfunction by new inhibitor of DPP4 in diabetic rats
Copyright © 2019. Published by Elsevier B.V..
BACKGROUND: Increased mortality due to type 2 diabetes mellitus (T2DM) has been associated with renal and/or cardiovascular dysfunction. Dipeptidyl dipeptidase-4 inhibitors (iDPP-4s) may exert cardioprotective effects through their pleiotropic actions via glucagon-like peptide 1-dependent mechanisms. In this study, the pharmacological profile of a new iDPP-4 (LASSBio-2124) was investigated in rats with cardiac and renal dysfunction induced by T2DM.
METHODS: T2DM was induced in rats by 2 weeks of a high-fat diet followed by intravenous injection of streptozotocin. Metabolic disturbance and cardiac, vascular, and renal dysfunction were analyzed in the experimental groups.
RESULTS: Sitagliptin and LASSBio-2124 administration after T2DM induction reduced elevated glucose levels to 319.8 ± 13.2 and 279.7 ± 17.8 mg/dL, respectively (p < 0.05). LASSBio-2124 also lowered the cholesterol and triglyceride levels from 76.8 ± 8.0 to 42.7 ± 3.2 mg/dL and from 229.7 ± 25.4 to 100.7 ± 17.1 mg/dL, in diabetic rats. Sitagliptin and LASSBio-2124 reversed the reduction of the plasma insulin level. LASSBio-2124 recovered the increased urinary flow in diabetic animals and reduced 24-h proteinuria from 23.7 ± 1.5 to 13.3 ± 2.8 mg (p < 0.05). It also reduced systolic and diastolic left-ventricular dysfunction in hearts from diabetic rats.
CONCLUSION: The effects of LASSBio-2124 were superior to those of sitagliptin in the cardiovascular systems of T2DM rats. This new prototype showed promise for the avoidance of comorbidities in a T2DM experimental model, and thus may constitute an innovative therapeutic agent for the treatment of these conditions in the clinical field in future.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:71 |
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| Enthalten in: |
Pharmacological reports : PR - 71(2019), 6 vom: 04. Dez., Seite 1190-1200 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Alves, Bryelle E O [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.04.2020 Date Revised 29.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.pharep.2019.07.005 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM30274374X |
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| 100 | 1 | |a Alves, Bryelle E O |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Reduction of cardiac and renal dysfunction by new inhibitor of DPP4 in diabetic rats |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 27.04.2020 | ||
| 500 | |a Date Revised 29.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019. Published by Elsevier B.V. | ||
| 520 | |a BACKGROUND: Increased mortality due to type 2 diabetes mellitus (T2DM) has been associated with renal and/or cardiovascular dysfunction. Dipeptidyl dipeptidase-4 inhibitors (iDPP-4s) may exert cardioprotective effects through their pleiotropic actions via glucagon-like peptide 1-dependent mechanisms. In this study, the pharmacological profile of a new iDPP-4 (LASSBio-2124) was investigated in rats with cardiac and renal dysfunction induced by T2DM | ||
| 520 | |a METHODS: T2DM was induced in rats by 2 weeks of a high-fat diet followed by intravenous injection of streptozotocin. Metabolic disturbance and cardiac, vascular, and renal dysfunction were analyzed in the experimental groups | ||
| 520 | |a RESULTS: Sitagliptin and LASSBio-2124 administration after T2DM induction reduced elevated glucose levels to 319.8 ± 13.2 and 279.7 ± 17.8 mg/dL, respectively (p < 0.05). LASSBio-2124 also lowered the cholesterol and triglyceride levels from 76.8 ± 8.0 to 42.7 ± 3.2 mg/dL and from 229.7 ± 25.4 to 100.7 ± 17.1 mg/dL, in diabetic rats. Sitagliptin and LASSBio-2124 reversed the reduction of the plasma insulin level. LASSBio-2124 recovered the increased urinary flow in diabetic animals and reduced 24-h proteinuria from 23.7 ± 1.5 to 13.3 ± 2.8 mg (p < 0.05). It also reduced systolic and diastolic left-ventricular dysfunction in hearts from diabetic rats | ||
| 520 | |a CONCLUSION: The effects of LASSBio-2124 were superior to those of sitagliptin in the cardiovascular systems of T2DM rats. This new prototype showed promise for the avoidance of comorbidities in a T2DM experimental model, and thus may constitute an innovative therapeutic agent for the treatment of these conditions in the clinical field in future | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Dipeptidyl dipeptidase-4 inhibitor | |
| 650 | 4 | |a Endothelial dysfunction | |
| 650 | 4 | |a Hypercaloric diet | |
| 650 | 4 | |a Left ventricular diastolic dysfunction | |
| 650 | 4 | |a Metabolic disturbance | |
| 650 | 4 | |a Renal dysfunction | |
| 650 | 4 | |a Type 2 diabetes | |
| 650 | 7 | |a Dipeptidyl-Peptidase IV Inhibitors |2 NLM | |
| 650 | 7 | |a Streptozocin |2 NLM | |
| 650 | 7 | |a 5W494URQ81 |2 NLM | |
| 650 | 7 | |a Glucagon-Like Peptide 1 |2 NLM | |
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| 650 | 7 | |a Sitagliptin Phosphate |2 NLM | |
| 650 | 7 | |a TS63EW8X6F |2 NLM | |
| 700 | 1 | |a de Alencar, Allan K N |e verfasserin |4 aut | |
| 700 | 1 | |a Gamba, Luis E R |e verfasserin |4 aut | |
| 700 | 1 | |a Trachez, Margarete M |e verfasserin |4 aut | |
| 700 | 1 | |a da Silva, Jaqueline S |e verfasserin |4 aut | |
| 700 | 1 | |a Araújo, Josenildo S C |e verfasserin |4 aut | |
| 700 | 1 | |a Montagnoli, Tadeu L |e verfasserin |4 aut | |
| 700 | 1 | |a Mendes, Luiza V P |e verfasserin |4 aut | |
| 700 | 1 | |a Pimentel-Coelho, Pedro M |e verfasserin |4 aut | |
| 700 | 1 | |a do M N Cunha, Valéria |e verfasserin |4 aut | |
| 700 | 1 | |a Mendez-Otero, Rosalia |e verfasserin |4 aut | |
| 700 | 1 | |a Oliveira, Gláucia M M |e verfasserin |4 aut | |
| 700 | 1 | |a Lima, Lídia M |e verfasserin |4 aut | |
| 700 | 1 | |a Barreiro, Eliezer J |e verfasserin |4 aut | |
| 700 | 1 | |a Sudo, Roberto T |e verfasserin |4 aut | |
| 700 | 1 | |a Zapata-Sudo, Gisele |e verfasserin |4 aut | |
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