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. β -cell failure is a main contributor to the development of T2DM. Oxidative stress and enhanced apoptosis play a critical role in pathogenesis of β -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 Monophosphate (cAMP) were immunoassayed in addition to determination 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 β -cell dysfunction associated with HFD-induced T2DM possibly by improving redox status, rescuing cAMP signaling and decreasing the level of TXNIP.