Abstract
Cardiovascular disease is the major cause of death in patients with diabetes. Current treatment strategies for diabetes rely on lifestyle changes and glucose control to prevent angiopathy and organ failure. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is used as an add-on therapy to insulin treatment. Exenatide also has multiple beneficial effects in addition to its hypoglycemic effects, such as preventing hepatic steatosis and protecting against cardiac injury from doxorubicin-induced cardiotoxicity or ischemic reperfusion. However, the mechanisms underlying the cardioprotective effects of exenatide in diabetes have not been fully clarified. To address this issue, we investigated the cardioprotective effects of exenatide in type 1 and type 2 diabetic mice. We found that exenatide simultaneously attenuated reactive oxidative species (ROS) production through increases in the antioxidant enzymes manganese dependent superoxide dismutase (MnSOD) and catalase. Moreover, exenatide decreased tumor protein P53 (p53) expression and prevented cell apoptosis in H9c2 cells. The presence of the catalase inhibitor 3-AT attenuated the effects of exenatide. Overall, the results strongly indicate that exenatide treatment may be protective against the development of diabetic cardiomyopathy.
Highlights
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia
Fasting blood glucose (FBG) levels in both T1DM and T2DM groups was increased compared to that in the CON group, and exenatide-treated mice showed decreased fasting blood glucose (FBG) levels compared to model animals (Figure 1B)
The intraperitoneal glucose tolerance test and Homeostasis model assessment (HOMA-IR) levels showed that exenatide improved glucose tolerance, insulin resistance and reduced the area under the curve (AUC) in T2DM animals (Figures 1C–E)
Summary
Cardiovascular disease is the major cause of death in diabetic patients. Patients with diabetes are at least 10 times more likely to suffer from heart dysfunction than their non-diabetic counterparts [1,2,3]. GLP-1 is an insulinotropic hormone released from intestinal L cells in response to nutrient ingestion, and it modulates glucose metabolism by affecting pancreatic islet secretions. It can be rapidly inactivated by the enzyme dipeptidyl peptidase IV in the circulation. Previous studies have shown that in addition to the hypoglycemic effect, exenatide reduced weight gain and alleviated hepatic steatosis in diabetic mice [4, 5].
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