الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
The worldwide prevalence of diabetes mellitus (DM) is increasing rapidly and dramatically. The World Health Organization (WHO) reported that the number of people with DM has risen from 108 million in 1980 to 422 million in 2014. DM occurrence has been rising more quickly in middle- and low-income nations. DM is a noteworthy reason of heart attacks, stroke blindness, kidney failure, and lower limb amputation. In 2016, an estimated 1.6 million deaths were legitimately attributed to DM. Another 2.2 million deaths were directly linked to high blood glucose in 2012. This means much more efforts should be invested to overcome the overgrowth of DM and its associated complications. The present study was conducted to investigate the potential influence of some pancreatic β-islets modulating drugs on experimentally-induced diabetes mellitus. DM was induced by single I.P. injection of 50 mg/kg streptozotocin (STZ) in male rats. Treatments were given once daily by oral route for 4 weeks starting from day one of confirmation of diabetes. Four drugs were selected to evaluate their antioxidant, anti-inflammatory, immunomodulatory, antiapoptotic and antihyperglycemic properties including; Sitagliptin (Januvia®), Imatinib mesylate (Gleevec®), Nilotinib hydrochloride (Tasigna®) and Crocin using biochemical, histopathological and immunohistochemical tools. Sitagliptin, crocin, imatinib and nilotinib improved DM indices in an animal model of experimentally-induced T1DM as seen in reduction of blood glucose which was associated with enhancement of insulin secretion and reduction of serum glucagon. Most importantly, their effect was associated with preservation of morphological characteristics of pancreatic β-islets. Sitagliptin, crocin, imatinib and nilotinib simultaneously targeted several key effectors and intracellular signaling pathways implicated in the pathogenic pathway of DM including, oxidative stress, caspase-3 expression and macrophage´s infiltration within pancreatic β-islets which may account for its observed therapeutic impact. Thus, by preservation of β-islets morphology and enhancement of β-islets integrity and secretory functions, these drugs can be proposed to be a novel therapeutic approach for management of DM. Further clinical investigations are required to verify the observed effect and determine the exact therapeutic doses.