الفهرس 
Review of LiteratureOnly 14 pages are availabe for public view
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Abstract
Type 2 diabetes mellitus (T2DM) is a complex disease characterized by insufficient insulin secretion from the β-cells coupled with insulin resistance (IR) in the target tissues. An accumulating body of evidence supports the role of autophagy, a self-protective mechanism performing a housekeeping role in removing misfolded proteins and damaged organelles, in the pathophysiology of T2DM. In addition, abnormal endoplasmic reticulum (ER) stress response that has been implicated as a cause of IR could also be affected by autophagic status in β-cells. So the present study was carried out to investigate whether autophagy is regulated in T2DM as well as to investigate the effect of ER stress reduction “using 4-PBA” or autophagy activation “using Rapamycin” on diabetic state using a rat model of T2DM with IR. Diabetes was developed in male wistar rats through feeding a high fat diet followed by intraperitoneal injection of streptozotocin (35mg/kg). Experimental animals were divided into 6 groups (10 each): normal group left without treatment, normal group orally administered with 4-PBA, normal group intraperitoneally injected with Rapa, diabetic group left without treatment, diabetic group orally administered with 4-PBA and diabetic group intraperitoneally injected with Rapa. Data revealed a state of hyperglycemia, hypoinsulinemia and IR in diabetic untreated animals. In addition, a decreased level of total antioxidant capacity as well as increased levels of lipid peroxidation and ER stress coupled with low level of autophagy have been observed in diabetic animals. Treatment of diabetic rats with either 4-PBA or rapamycin improved significantly the states of hyperglycemia and dyslipidemia, increased the antioxidant capacity and decreased the level of lipid peroxidation in both blood and pancreas of treated animals, compared to untreated group. Furthermore, the applied treatments reduced the ER stress and increased the autophagic flux in treated animals. These findings were further supported by electron microscopy study on pancreatic sections of treated animals. The obtained improvements were attributed mainly to the induction of autophagy with subsequent regulation of ER stress-oxidative activation and prevention of β-cell apoptosis.