Abstract
Our previous study in Goto-Kakizaki (GK) type 2 diabetic rats provided significant evidence that aspirin treatment improves pancreatic β-cell function by reducing inflammatory responses and improving glucose tolerance. In the present study, we aimed to elucidate the mechanism of action of aspirin on the pathophysiology and progression of type 2 diabetic complications in the heart and pancreas of insulin-resistant GK rats. Aspirin treatment demonstrated a reduction in mitochondrial reactive oxygen species (ROS) production and lipid peroxidation, accompanied by improved redox homeostasis. Furthermore, the recovery of metabolic and mitochondrial functions, as well as cytochrome P450 enzyme activities, which were altered in the pancreas and heart of GK rats, were observed. Aspirin treatment brought the activity of CYP 2E1 to the control level in both tissues, whereas the CYP 3A4 level decreased only in the pancreas. This suggests the tissue-specific differential metabolism of substrates in these rats. The recovery of redox homeostasis could be the key target in the improvement of oxidative-stress-dependent alterations in mitochondrial functions which, in turn, facilitated improved energy metabolism in these tissues in the aspirin-treated GK rats. These results may have implications in determining the therapeutic use of aspirin, either alone or in combination with other clinically approved therapies, in insulin-resistant type 2 diabetes.
Highlights
The prevalence of diabetes has been steadily increasing all over the world, as a result of which it has become an epidemic in some countries
Aspirin treatment markedly reduced the production of reactive oxygen species (ROS) in the hearts of GK rats, though a moderate reduction was seen in the pancreas
We have demonstrated an increase in energy metabolism and mitochondrial function after aspirin treatment, as well as alterations in the activities of cytochrome P450 and GSH-conjugating drug-metabolizing enzymes
Summary
The prevalence of diabetes has been steadily increasing all over the world, as a result of which it has become an epidemic in some countries. The global prevalence of diabetes in 2019 was estimated to be 463 million, rising to 578 million by 2030 and 700 million by 2045, with the prevalence being higher in urban than in rural areas and in high-income than in low-income countries [1]. Diabetes is associated with multiple metabolic complications, characterized by intensive metabolic disturbances in different metabolic pathways, in most tissues resulting in high morbidity and mortality [3]. These complications are wide-ranging and are grouped as ‘microvascular’, which includes retinopathy, nephropathy and neuropathy, and the major ‘macrovascular’ complications include accelerated cardiovascular disease resulting in myocardial infarction and cerebrovascular disease manifesting as strokes [4,5]. Type 2 diabetes (T2D) was considered less complicated until a few years back, but this idea has changed since the life expectancy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
