الفهرس 
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Abstract
Diabetes mellitus is a group of metabolic diseases in which the patients have high blood glucose levels. There are two major types of diabetes. Type 1 diabetes , previously called juvenile iabetes or insulin-dependent diabetes, develops on the basis of autoim-mune destruction of pancreatic β-cells. Type 2 diabetes is the most common form of diabetes and accounts for approximately 85–90% of all diabetic patients. In Type 2 DM, hyperglycemia reults from acombination of impaired insulin secretion and insulin resistance . Diabetes patients often develop macro- vascular and/or micro-vascular complications. Diabetic nephropathy (DN) is one of serious complications and occurs in 30–40% of diabetic patients. This diabetic complication is characterized by pathophysiological changes in glomerular hyperfiltration, renal hypertrophy, tubular function and then progress to proteinuria and reduction of glomerular filtration rate (GFR). The patients with DN exhibit persistent proteinuria, hypertension, declining renal function, and increased premature mortality largely as a result of cardiovascular disease. DN is the most common single cause of end-stage renal disease (ESRD). Once overt DN occurs, it progresses slowly or rapidly to the most advanced stage of chronic kidney disease which needs dialysis or transplantation treatment .
The treatment cost for diabetes patients has been increasing staggering in the recent decades and becomes a further burden of the healthcare system. Diabetes and DN are multi-factorial diseases,which are influenced by both genetic and environmental factors . Diabetic nephropathy is a progress disease, which is categorized into stages based upon urinary albumin excretion (UAE) values. The early phase, which can be reversed, is microalbuminuria. The reduction of renal function beginswith proteinuria. Therefore, identification of the susceptibility genes in development of diabetes and diabetic complications and investigation of their roles are of importance to provide useful information for improvement of the prevention and medication programs. Intercellular adhesion molecule 1 (ICAM1) is a cell surface glycoprotein and expressed in endothelial cells and leukocytes in the immune system. The ICAM1 gene is located in chromosome 19p13.2 and spans 15,775 base pairs along the short arm of this chromosome. ICAM1 protein is 505 amino acids in the length, the molecule weights between 80 and 114 kDa depending upon the levels of glycosylation, which varies among cell types and environments. By using the approach of genome-wide scan and linkage anal- yses, several chromosomal regions including 19p13 have been predicted to link with diabetes and DN . Circulating levels of soluble ICAM-1 is elevated in diabetic patients, and the increased lipoprotein oxidation in diabetes or in states of chronic hyperglycemia may be responsible for the high expression of circulating adhesion molecules. Indeed, whereas acute hyperglycemia induces an increase in circulating sICAM-1 levels in normoglycemic individuals, elevated levels of plasma sICAM-1 are also found in type 2 diabetic patients. These findings demonstrate that hyperglycemia leads to an increase in the adhesive properties of endothelial cells; however, this can be normalized by insulin treatment. Acute hyperglycemia induces increased plasma levels of circulating ICAM-1, whereas a high-fat meal significantly increases plasma levels of ICAM-1. Clinical investigation has demonstrated that soluble ICAM1 levels in stored blood samples from Type 1 diabetic patients are higher compared to non-diabetic control subjects. Furthermore, it was reported that soluble ICAM1 levels are associated with all-caused mortality and cardiovascular morbidity in Type 1DM patients with DN. The similar findings have been observed in Type 2 DM patients. Soluble ICAM1 levels are significantly correlated with albuminuria in Type 2DM patients. T2DM patients with diabetic micro-angiopathic complications have higher soluble ICAM1 levels in comparison with diabetic group without micro-angiopathic complications and healthy control subjects. Therefore, ICAM1 may play a role in the development of diabetes DN . In adiabetic condition with hyperglycemia ,the ICAM1 gene transcription in the nuclei is increased and the ICAM1 gene expression on the surface of endothelium cells is up-regulated. ICAM1 binding activity with LFA-1 is increased and morelymphocytes from blood are trans- ferred into cells in glomeruli and peritubular capillaries of nephron in kidney. Consequently, injure of kidney glomeruli and tubular occurs and the proteins are excreted to urine. As we described above, genetic and biological studies have implicated that ICAM1 plays a role in the development of diabetes and DN. First, the ICAM1 gene is located in a linkage region with diabetes and DN. Second, theK469E polymorphism in the ICAM1 gene is associated with diabetes and DN. Third, serum ICAM1 levels are gradually increased from low levels in normal albuminuria to high levels in micro-albuminuria and to even higher levels in proteinuria. ICAM1 is a molecule involved in many pathways including anti-inflammation. Although the picture of ICAM1 involvement and interaction is complex, experiments have indicated that inhibition of the ICAM1 gene expression may improve the progress of diabetes and DN. This molecule is most likely a useful biomarker for prediction of endothelial dysfunction in diabetes and DN. It is suggested that ICAM1 may be a good candidate as target for drug development. Inhibition of ICAM1 gene activity may benefit in treatment of diabetes and DN.