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Modulation of Autophagy Signal Pathway in Type 2 Diabetes Mellitus Rat Model Using Phytochemical Extracts


 
 
 Type 2 DM is a chronic metabolic disease characterized by insulin resistance and beta cell dysfunction. It is an extremely heterogeneous disease in which the insulin resistance and beta cell dysfunction resulted from environmental and genetic factor. Type 2 diabetes is the most prevalent form of diabetes worldwide and account for 90% of cases globally. It represents a major public health threat and considered as a principal cause of morbidity and mortality affecting almost 6% of the world’s population. Patients with type 2 diabetes usually have insulin resistance and relative insulin deficiency and are often associated with a strong genetic predisposition.
 
 
 
 To retrieve potential miRNA-associated ceRNAs Linked to autophagy, insulin resistance and type 2 DM from Public microarray databases followed by validation of the chosen network in animal model. To evaluate the efficacy of Isorhamentin as a potential therapeutic strategy to modulate the autophagy pathway and IR in type 2 DM.
 
 
 
 This study was done at Medical Biochemistry Department, Faculty of Medicine, Ain Shams University during the period from December 2019 – June 2020 and included 50 wistar male rats. 50 Male Wistar rats weighed (140-150g), age nearly two months, were purchased from the Holding Company for Biological Products and Vaccines. They were acclimatized to laboratory environment for at least one week with free access to water and food before induction of diabetes. Experiment for eight weeks duration was planned after a pilot study was performed for determination of the most effective and least toxic STZ dose.
 
 
 
 Our study demonstrated that “Isorhamentin” can be potential treatment in type 2 diabetes mellitus through modulation of Autophagy signaling pathway related genes and ceRNA network. Isorhamentin down-regulates the expression of m-tor mRNA and it up-regulates the expression of miR-1.
 
 
 
 The results of our study Support our previous hypothesis that miR-1 miRNA and mTOR mRNA act as ceRNA network and might play an important role in the pathogenesis of autophagy and insulin resistance and T2DM.And could be potential therapeutic target by isorhamentin to modulate the expression of the deregulated network in type 2 DM.
