الفهرس 
Type 2 Diabetes Mellitus (T2DM)Only 14 pages are availabe for public view
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Abstract
Type 2 diabetes mellitus (T2DM) is metabolic disorder which involves dysregulation of carbohydrate, lipid, and protein metabolism and is characterized by hyperglycemia as a result of impaired insulin secretion from the pancreatic β-cells, insulin resistance or a combination of both. T2DM occurs as a result of chronic overnutriton and physical inactivity in individuals with underlying genetic and acquired predispositions to both insulin resistance and β-cell dysfunction. The high fat diet-fed rodent model has been used in many studies to induce insulin resistance with overt T2DM. Therefore, among all experimental models of T2DM, high fat diet-induced T2DM is the most parallel to the natural pathophysiology of the disease in humans. In response to insulin resistance, pancreatic islets usually respond by β-cell compensation which involves both expansion of the β-cell mass and enhanced β-cell function. Over time, β-cell compensation fails, resulting in a progressive decline in β-cell function which finally ends with established T2DM. Several pathological processes contribute to the development of this β-cell failure including glucolipotoxicity-induced oxidative stress and enhanced β-cell apoptosis. Thioredoxin interacting protein (TXNIP) has been linked to oxidative stress and apoptosis via interaction with & inhibition of thioredoxin (TXR) which is a ubiquitous thiol oxidoreductase essential for redox homeostasis, TRX also exerts antiapoptotic action via binding and inhibiting apoptosis signal-regulating kinase-1 (ASK-1). Cellular stress such as oxidative stress induces TXNIP over expression & translocation from nucleus to cytosol & mitochondria where it interacts with TXR subsequently, blocking its antioxidant power and releasing ASK-1 from its inhibitory effect. In pancreatic β-cell, high glucose was found to be the main inducer of TXNIP gene expression via a unique carbohydrate response element binding protein (ChREBP). In addition, decreased cyclic adenosine monophosphate (cAMP) levels was associated with increased protein level of TXNIP. cAMP is a ubiquitous well studied second messenger which in addition to its physiological effects has been found to be antiapoptotic in many tissues including pancreatic β-cells. Alpha lipoic acid (ALA) is a naturally occurring short-chain fatty acid that contains a thiol bond & has powerful antioxidant & free radical scavenging properties. Recently, ALA has drawn much attention since many studies reported an antiapoptotic effect in many tissues exerted by ALA treatment.