Effect of Alpha Lipoic Acid on Apoptotic Mechanisms and Oxidative Stress in Pancreatic Cells of High Fat Diet Induced Type II Diabetes Mellitus in Rats

Abstract
Background: Type 2 Diabetes Mellitus (T2DM) is a worldwide health problem with significant morbidity and mortality. b-cell failure is a main contributor to the develop-ment of T2DM. Oxidative stress and enhanced apoptosis play a critical role in pathogenesis of b-cell failure. Recently, Alpha Lipoic Acid (ALA), a universal antioxidant, has been shown to exert anti-apoptotic actions.
Aim of Study: The present study was aimed to evaluate the possible ameliorative effect of ALA against pancreatic tissue oxidative stress and apoptotic mechanisms in a rat model of High Fat Diet (HFD)-induced T2DM.
Material and Methods: Eighty albino rats were included, 20 rats received a standard diet and served as normal control group (Group I) and 60 rats were fed a homemade HFD for 6 months for induction of T2DM, only diabetics (40 rats) were included and divided into 2 groups; 20 continued to receive HFD for further 21 days, served as diabetic untreated group (Group II); 20 received ALA (50mg/kg i.p) for 21 days and served as ALA-treated group (Group III). Thioredoxin Interacting Protein (TXNIP) and cyclic Adenosine Monophos-phate (cAMP) were immunoassayed in addition to determina-tion of levels of plasma fructosamine, fasting blood glucose (FBG) and pancreatic tissue Malondialdehyde (MDA) along with pancreatic catalase and Superoxide Dismutase (SOD) activities.
Results: ALA treatment showed significant improvement in fructosamine and FBG levels, decreased MDA level and increased catalase and SOD activities, in addition to increased cAMP level and decreased TXNIP level.
Conclusion: We concluded that ALA has the ability to interfere with b-cell dysfunction associated with HFD-induced T2DM possibly by improving redox status, rescuing cAMP signaling and decreasing the level of TXNIP.