Liraglutide Attenuates Diabetic Cardiomyopathy via the ILK/PI3K/AKT/PTEN Signaling Pathway in Rats with Streptozotocin-Induced Type 2 Diabetes Mellitus
One of the possible candidates for the treatment of diabetic cardiomyopathy is liraglutide, a glucagon-like peptide-1 receptor (GLP1R) agonist. In this study, the impacts of liraglutide on the integrin-linked kinase (ILK)-related PI3K/AKT axis in rats with type 2 diabetes induced via streptozotocin...
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MDPI AG
2024-03-01
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| author | Shatha M. Alobaid Rahaf M. Alshahrani Asma S. Alonazi Nawal M. Alrasheed Maha A. Alamin Tahani K. Alshammari Anfal F. Bin Dayel Doaa M. Elnagar Rana R. Alotaibi Lama A. Almuthnabi Dalia H. Almasud Shahad E. Al-Ammar Shahad O. Almadhi Reema A. Almalke Nouf T. Aldamri Hanan K. Alghibiwi Dalal A. Alkhelb Nouf M. Alrasheed |
| author_facet | Shatha M. Alobaid Rahaf M. Alshahrani Asma S. Alonazi Nawal M. Alrasheed Maha A. Alamin Tahani K. Alshammari Anfal F. Bin Dayel Doaa M. Elnagar Rana R. Alotaibi Lama A. Almuthnabi Dalia H. Almasud Shahad E. Al-Ammar Shahad O. Almadhi Reema A. Almalke Nouf T. Aldamri Hanan K. Alghibiwi Dalal A. Alkhelb Nouf M. Alrasheed |
| author_sort | Shatha M. Alobaid |
| collection | DOAJ |
| description | One of the possible candidates for the treatment of diabetic cardiomyopathy is liraglutide, a glucagon-like peptide-1 receptor (GLP1R) agonist. In this study, the impacts of liraglutide on the integrin-linked kinase (ILK)-related PI3K/AKT axis in rats with type 2 diabetes induced via streptozotocin were examined. Twenty-four Wistar albino rats were distributed in four different groups, and a high-fat diet and streptozotocin were used to induce type 2 in two groups. Rats in the untreated control groups were administered 0.9% NaCl solution over a 6-week period, and those in the treatment groups were administered 0.9% NaCl for 3 weeks, followed by subcutaneous injection of liraglutide (150 μg/kg) for an additional 3 weeks. In the liraglutide-treated diabetic group, the heart-to-body weight ratio was significantly reduced, levels of cardiac biomarkers, troponin I and creatine-kinase-MB, were improved; activities of antioxidant enzymes, glutathione peroxidase and superoxide dismutase, were increased; and levels of malondialdehyde were decreased. Western blotting and immunohistochemical studies revealed increased levels of ILK, P-PI3K, P-AKT, and BCL2, as well as those of caspase 3, BAX, and P-PTEN, indicating mitigation of cardiomyocyte apoptosis. Our results show that liraglutide, by targeting GLP1Rs, enhances the expression of proteins in the ILK/PI3K/AKT/PTEN pathway and thereby exerts its cardioprotective effects in rats with DCM. |
| first_indexed | 2024-04-24T17:54:36Z |
| format | Article |
| id | doaj.art-095cdbd134b645aaadab72aa3b31cd32 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-04-24T17:54:36Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-095cdbd134b645aaadab72aa3b31cd322024-03-27T13:59:25ZengMDPI AGPharmaceuticals1424-82472024-03-0117337410.3390/ph17030374Liraglutide Attenuates Diabetic Cardiomyopathy via the ILK/PI3K/AKT/PTEN Signaling Pathway in Rats with Streptozotocin-Induced Type 2 Diabetes MellitusShatha M. Alobaid0Rahaf M. Alshahrani1Asma S. Alonazi2Nawal M. Alrasheed3Maha A. Alamin4Tahani K. Alshammari5Anfal F. Bin Dayel6Doaa M. Elnagar7Rana R. Alotaibi8Lama A. Almuthnabi9Dalia H. Almasud10Shahad E. Al-Ammar11Shahad O. Almadhi12Reema A. Almalke13Nouf T. Aldamri14Hanan K. Alghibiwi15Dalal A. Alkhelb16Nouf M. Alrasheed17PharmD Program, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaPharmD Program, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaPharmD Program, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaPharmD Program, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaPharmD Program, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaPharmD Program, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaPharmD Program, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaPharmD Program, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaOne of the possible candidates for the treatment of diabetic cardiomyopathy is liraglutide, a glucagon-like peptide-1 receptor (GLP1R) agonist. In this study, the impacts of liraglutide on the integrin-linked kinase (ILK)-related PI3K/AKT axis in rats with type 2 diabetes induced via streptozotocin were examined. Twenty-four Wistar albino rats were distributed in four different groups, and a high-fat diet and streptozotocin were used to induce type 2 in two groups. Rats in the untreated control groups were administered 0.9% NaCl solution over a 6-week period, and those in the treatment groups were administered 0.9% NaCl for 3 weeks, followed by subcutaneous injection of liraglutide (150 μg/kg) for an additional 3 weeks. In the liraglutide-treated diabetic group, the heart-to-body weight ratio was significantly reduced, levels of cardiac biomarkers, troponin I and creatine-kinase-MB, were improved; activities of antioxidant enzymes, glutathione peroxidase and superoxide dismutase, were increased; and levels of malondialdehyde were decreased. Western blotting and immunohistochemical studies revealed increased levels of ILK, P-PI3K, P-AKT, and BCL2, as well as those of caspase 3, BAX, and P-PTEN, indicating mitigation of cardiomyocyte apoptosis. Our results show that liraglutide, by targeting GLP1Rs, enhances the expression of proteins in the ILK/PI3K/AKT/PTEN pathway and thereby exerts its cardioprotective effects in rats with DCM.https://www.mdpi.com/1424-8247/17/3/374glucagon-like peptide-1 analogdiabetic cardiomyopathystreptozotocin-induced type 2 diabetesintegrin-linked kinasephosphatidylinositol 3-kinaseprotein kinase B |
| spellingShingle | Shatha M. Alobaid Rahaf M. Alshahrani Asma S. Alonazi Nawal M. Alrasheed Maha A. Alamin Tahani K. Alshammari Anfal F. Bin Dayel Doaa M. Elnagar Rana R. Alotaibi Lama A. Almuthnabi Dalia H. Almasud Shahad E. Al-Ammar Shahad O. Almadhi Reema A. Almalke Nouf T. Aldamri Hanan K. Alghibiwi Dalal A. Alkhelb Nouf M. Alrasheed Liraglutide Attenuates Diabetic Cardiomyopathy via the ILK/PI3K/AKT/PTEN Signaling Pathway in Rats with Streptozotocin-Induced Type 2 Diabetes Mellitus Pharmaceuticals glucagon-like peptide-1 analog diabetic cardiomyopathy streptozotocin-induced type 2 diabetes integrin-linked kinase phosphatidylinositol 3-kinase protein kinase B |
| title | Liraglutide Attenuates Diabetic Cardiomyopathy via the ILK/PI3K/AKT/PTEN Signaling Pathway in Rats with Streptozotocin-Induced Type 2 Diabetes Mellitus |
| title_full | Liraglutide Attenuates Diabetic Cardiomyopathy via the ILK/PI3K/AKT/PTEN Signaling Pathway in Rats with Streptozotocin-Induced Type 2 Diabetes Mellitus |
| title_fullStr | Liraglutide Attenuates Diabetic Cardiomyopathy via the ILK/PI3K/AKT/PTEN Signaling Pathway in Rats with Streptozotocin-Induced Type 2 Diabetes Mellitus |
| title_full_unstemmed | Liraglutide Attenuates Diabetic Cardiomyopathy via the ILK/PI3K/AKT/PTEN Signaling Pathway in Rats with Streptozotocin-Induced Type 2 Diabetes Mellitus |
| title_short | Liraglutide Attenuates Diabetic Cardiomyopathy via the ILK/PI3K/AKT/PTEN Signaling Pathway in Rats with Streptozotocin-Induced Type 2 Diabetes Mellitus |
| title_sort | liraglutide attenuates diabetic cardiomyopathy via the ilk pi3k akt pten signaling pathway in rats with streptozotocin induced type 2 diabetes mellitus |
| topic | glucagon-like peptide-1 analog diabetic cardiomyopathy streptozotocin-induced type 2 diabetes integrin-linked kinase phosphatidylinositol 3-kinase protein kinase B |
| url | https://www.mdpi.com/1424-8247/17/3/374 |
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