Journal Article

Liraglutide Attenuates Diabetic Cardiomyopathy via the ILK/PI3K/AKT/PTEN Signaling Pathway in Rats with Streptozotocin-Induced Type 2 Diabetes Mellitus

Almuthnabi, Lama A., Alghibiwi, Hanan K., Elnagar, Doaa M., Alrasheed, Nawal M., Alotaibi, Rana R., Alrasheed, Nouf M., Alshammari, Tahani K., Bin Dayel, Anfal F., Almalke, Reema A., Almasud, Dalia H., Almadhi, Shahad O., Aldamri, Nouf T., Alkhelb, Dalal A., Alamin, Maha A., Al-Ammar, Shahad E., Alobaid, Shatha M., Alshahrani, Rahaf M., Alonazi, Asma S.

2024

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Biomarkers / Cardiomyocytes / Cardiomyopathy / Cardiovascular disease / Cellular signal transduction / Complications and side effects / Diabetes / Diabetic angiopathies / diabetic cardiomyopathy / Drug therapy / glucagon-like peptide-1 analog / Glucose / Health aspects / Heart attacks / Heart diseases / Heart failure / Hypoglycemia / Insulin resistance / integrin-linked kinase / Kinases / Liraglutide / phosphatidylinositol 3-kinase / Phosphorylation / protein kinase B / Protein kinases / streptozotocin-induced type 2 diabetes / Testing / Type 2 diabetes