Alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbits
Abstract Background There are increasing evidence that left ventricle diastolic dysfunction is the initial functional alteration in the diabetic myocardium. In this study, we hypothesized that alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function and structu...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-12-01
|
| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12933-018-0803-z |
| _version_ | 1818239189313912832 |
|---|---|
| author | Xiaowei Zhang Zhiwei Zhang Yajuan Yang Ya Suo Ruimeng Liu Jiuchun Qiu Yungang Zhao Ning Jiang Changle Liu Gary Tse Guangping Li Tong Liu |
| author_facet | Xiaowei Zhang Zhiwei Zhang Yajuan Yang Ya Suo Ruimeng Liu Jiuchun Qiu Yungang Zhao Ning Jiang Changle Liu Gary Tse Guangping Li Tong Liu |
| author_sort | Xiaowei Zhang |
| collection | DOAJ |
| description | Abstract Background There are increasing evidence that left ventricle diastolic dysfunction is the initial functional alteration in the diabetic myocardium. In this study, we hypothesized that alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function and structure in diabetic rabbits. Methods A total of 30 rabbits were randomized into control group (CON, n = 10), alloxan-induced diabetic group (DM, n = 10) and alogliptin-treated (12.5 mg/kd/day for 12 weeks) diabetic group (DM-A, n = 10). Echocardiographic and hemodynamic studies were performed in vivo. Mitochondrial morphology, respiratory function, membrane potential and reactive oxygen species (ROS) generation rate of left ventricular tissue were assessed. The serum concentrations of glucagon-like peptide-1, insulin, inflammatory and oxidative stress markers were measured. Protein expression of TGF-β1, NF-κB p65 and mitochondrial biogenesis related proteins were determined by Western blotting. Results DM rabbits exhibited left ventricular hypertrophy, left atrial dilation, increased E/e′ ratio and normal left ventricular ejection fraction. Elevated left ventricular end diastolic pressure combined with decreased maximal decreasing rate of left intraventricular pressure (− dp/dtmax) were observed. Alogliptin alleviated ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction in diabetic rabbits. These changes were associated with decreased mitochondrial ROS production rate, prevented mitochondrial membrane depolarization and improved mitochondrial swelling. It also improved mitochondrial biogenesis by PGC-1α/NRF1/Tfam signaling pathway. Conclusions The DPP-4 inhibitor alogliptin prevents cardiac diastolic dysfunction by inhibiting ventricular remodeling, explicable by improved mitochondrial function and increased mitochondrial biogenesis. |
| first_indexed | 2024-12-12T12:53:35Z |
| format | Article |
| id | doaj.art-f711913d27074c488fea9c0dc687fcc2 |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-12-12T12:53:35Z |
| publishDate | 2018-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-f711913d27074c488fea9c0dc687fcc22022-12-22T00:23:57ZengBMCCardiovascular Diabetology1475-28402018-12-0117111210.1186/s12933-018-0803-zAlogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbitsXiaowei Zhang0Zhiwei Zhang1Yajuan Yang2Ya Suo3Ruimeng Liu4Jiuchun Qiu5Yungang Zhao6Ning Jiang7Changle Liu8Gary Tse9Guangping Li10Tong Liu11Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Exercise Physiology and Sports Medicine, Department of Health & Exercise Science, Tianjin University of SportTianjin Key Laboratory of Exercise Physiology and Sports Medicine, Department of Health & Exercise Science, Tianjin University of SportTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical UniversityDepartment of Medicine and Therapeutics, Chinese University of Hong KongTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical UniversityTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical UniversityAbstract Background There are increasing evidence that left ventricle diastolic dysfunction is the initial functional alteration in the diabetic myocardium. In this study, we hypothesized that alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function and structure in diabetic rabbits. Methods A total of 30 rabbits were randomized into control group (CON, n = 10), alloxan-induced diabetic group (DM, n = 10) and alogliptin-treated (12.5 mg/kd/day for 12 weeks) diabetic group (DM-A, n = 10). Echocardiographic and hemodynamic studies were performed in vivo. Mitochondrial morphology, respiratory function, membrane potential and reactive oxygen species (ROS) generation rate of left ventricular tissue were assessed. The serum concentrations of glucagon-like peptide-1, insulin, inflammatory and oxidative stress markers were measured. Protein expression of TGF-β1, NF-κB p65 and mitochondrial biogenesis related proteins were determined by Western blotting. Results DM rabbits exhibited left ventricular hypertrophy, left atrial dilation, increased E/e′ ratio and normal left ventricular ejection fraction. Elevated left ventricular end diastolic pressure combined with decreased maximal decreasing rate of left intraventricular pressure (− dp/dtmax) were observed. Alogliptin alleviated ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction in diabetic rabbits. These changes were associated with decreased mitochondrial ROS production rate, prevented mitochondrial membrane depolarization and improved mitochondrial swelling. It also improved mitochondrial biogenesis by PGC-1α/NRF1/Tfam signaling pathway. Conclusions The DPP-4 inhibitor alogliptin prevents cardiac diastolic dysfunction by inhibiting ventricular remodeling, explicable by improved mitochondrial function and increased mitochondrial biogenesis.http://link.springer.com/article/10.1186/s12933-018-0803-zDipeptidyl peptidase-4 inhibitorsDiabetic cardiomyopathyDiabetes mellitusMitochondrial functionMitochondrial biogenesis |
| spellingShingle | Xiaowei Zhang Zhiwei Zhang Yajuan Yang Ya Suo Ruimeng Liu Jiuchun Qiu Yungang Zhao Ning Jiang Changle Liu Gary Tse Guangping Li Tong Liu Alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbits Cardiovascular Diabetology Dipeptidyl peptidase-4 inhibitors Diabetic cardiomyopathy Diabetes mellitus Mitochondrial function Mitochondrial biogenesis |
| title | Alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbits |
| title_full | Alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbits |
| title_fullStr | Alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbits |
| title_full_unstemmed | Alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbits |
| title_short | Alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbits |
| title_sort | alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbits |
| topic | Dipeptidyl peptidase-4 inhibitors Diabetic cardiomyopathy Diabetes mellitus Mitochondrial function Mitochondrial biogenesis |
| url | http://link.springer.com/article/10.1186/s12933-018-0803-z |
| work_keys_str_mv | AT xiaoweizhang alogliptinpreventsdiastolicdysfunctionandpreservesleftventricularmitochondrialfunctionindiabeticrabbits AT zhiweizhang alogliptinpreventsdiastolicdysfunctionandpreservesleftventricularmitochondrialfunctionindiabeticrabbits AT yajuanyang alogliptinpreventsdiastolicdysfunctionandpreservesleftventricularmitochondrialfunctionindiabeticrabbits AT yasuo alogliptinpreventsdiastolicdysfunctionandpreservesleftventricularmitochondrialfunctionindiabeticrabbits AT ruimengliu alogliptinpreventsdiastolicdysfunctionandpreservesleftventricularmitochondrialfunctionindiabeticrabbits AT jiuchunqiu alogliptinpreventsdiastolicdysfunctionandpreservesleftventricularmitochondrialfunctionindiabeticrabbits AT yungangzhao alogliptinpreventsdiastolicdysfunctionandpreservesleftventricularmitochondrialfunctionindiabeticrabbits AT ningjiang alogliptinpreventsdiastolicdysfunctionandpreservesleftventricularmitochondrialfunctionindiabeticrabbits AT changleliu alogliptinpreventsdiastolicdysfunctionandpreservesleftventricularmitochondrialfunctionindiabeticrabbits AT garytse alogliptinpreventsdiastolicdysfunctionandpreservesleftventricularmitochondrialfunctionindiabeticrabbits AT guangpingli alogliptinpreventsdiastolicdysfunctionandpreservesleftventricularmitochondrialfunctionindiabeticrabbits AT tongliu alogliptinpreventsdiastolicdysfunctionandpreservesleftventricularmitochondrialfunctionindiabeticrabbits |