Oxidative stress is associated with diabetes mellitus, a condition characterized by increased prevalence and progression rate of cardiovascular disease. NFE2-related factor 2 (Nrf2) is a master regulator of cellular d...Oxidative stress is associated with diabetes mellitus, a condition characterized by increased prevalence and progression rate of cardiovascular disease. NFE2-related factor 2 (Nrf2) is a master regulator of cellular detoxification responses and redox status. The aim of this study was to examine associations between type 2 Diabetes Mellitus (T2DM), oxidative stress and the expression of NFE2-related factor 2 (Nrf2) in a population of diabetic patients living in Juana Koslay City, San Luis, Argentina. In addition, we evaluated the functional relevance of Nrf2 by measuring the HO-1 expression among persons with type 2 diabetes. We measured clinical and biochemical parameters related to lipid metabolism and oxidative stress in a population of Type 2 Diabetes Mellitus patients (T2DM, n = 40) and controls (Co, n = 30). Compared to Co, T2DM patients had higher fasting serum glucose, glycated hemoglobin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and thiobarbituric acid reactive substances and lower high-density lipoprotein cholesterol. T2DM individuals had also higher atherogenic index and body mass index than controls. We also founded that HO-1 mRNA in whole blood was lower in T2DM than controls, suggesting that T2DM may have an altered antioxidant response to oxidative stress. Interestingly, we found reduced Nrf2 mRNA in whole blood from T2DM compared to Co. The results from this study provide novel evidence that genes associated to antioxidant defense mechanisms are markedly reduced in patients with type 2 diabetes, and that the reduction in the expression of these genes could be associated to hyperglycemia and increased levels of MDA. Linear regression analysis revealed that there was a strong and positive correlation between the changes of Nrf2 and HO-1 expression levels.展开更多
The scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor involved in reverse cholesterol transport. Some studies reported the association to be stronger in the presence of diabetes. T...The scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor involved in reverse cholesterol transport. Some studies reported the association to be stronger in the presence of diabetes. The full length gene encoding SR-BI is comprised in 13 exons that are alternatively spliced to produce two major transcripts: the full length SR-BI and the splice variant SR-BII, in which exon 12 is skipped. Considering that type 2 diabetes status is characterized by changes in the concentration of plasma lipids, modifications in lipoprotein size and composition, which may be important modulators of the SR-BI expression;the aims of the study were to examine the influence of SR-BI polymorphism (rs838895) on lipid profile and SR-BI mRNA expression in a population of diabetic patients living in Juana Koslay City. Blood samples were drawn from controls (n = 40) and Type 2 diabetic patients (n = 66) and DNA and total RNA were obtained. SR-BI mRNA expression was measured by RT-PCR and SR-BI polymorphism was detected by Tetra Primer ARMSPCR. Compared to controls, diabetic patients had higher fasting serum glucose, glycated hemoglobin, triglycerides, total cholesterol, lowdensity lipoprotein cholesterol, and lower highdensity lipoprotein cholesterol. SR-BI mRNA expression was lower in T2DM when compared to controls, suggesting that the hyperglycemia presents in T2DM patients down-regulates SR-BI mRNA expression. Interestingly, we found that decreased SR-BI expression resulted in markedly increased plasma LDL concentrations in T2DM subjects, and the overexpression of SRBII isoform is responsible for the markedly increased plasma LDL-c concentrations. The polymorphism (rs838895) did not modify the mRNA level of SR-BI in leucocytes from control and diabetic patients. This study provides novel evidence suggesting that hyperglycemia may affect reverse cholesterol transport by controlling SRBI expression in diabetic patients. LDL cholesterol levels are associated with low SR-BI mRNA expression in T2DM.展开更多
文摘Oxidative stress is associated with diabetes mellitus, a condition characterized by increased prevalence and progression rate of cardiovascular disease. NFE2-related factor 2 (Nrf2) is a master regulator of cellular detoxification responses and redox status. The aim of this study was to examine associations between type 2 Diabetes Mellitus (T2DM), oxidative stress and the expression of NFE2-related factor 2 (Nrf2) in a population of diabetic patients living in Juana Koslay City, San Luis, Argentina. In addition, we evaluated the functional relevance of Nrf2 by measuring the HO-1 expression among persons with type 2 diabetes. We measured clinical and biochemical parameters related to lipid metabolism and oxidative stress in a population of Type 2 Diabetes Mellitus patients (T2DM, n = 40) and controls (Co, n = 30). Compared to Co, T2DM patients had higher fasting serum glucose, glycated hemoglobin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and thiobarbituric acid reactive substances and lower high-density lipoprotein cholesterol. T2DM individuals had also higher atherogenic index and body mass index than controls. We also founded that HO-1 mRNA in whole blood was lower in T2DM than controls, suggesting that T2DM may have an altered antioxidant response to oxidative stress. Interestingly, we found reduced Nrf2 mRNA in whole blood from T2DM compared to Co. The results from this study provide novel evidence that genes associated to antioxidant defense mechanisms are markedly reduced in patients with type 2 diabetes, and that the reduction in the expression of these genes could be associated to hyperglycemia and increased levels of MDA. Linear regression analysis revealed that there was a strong and positive correlation between the changes of Nrf2 and HO-1 expression levels.
文摘The scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor involved in reverse cholesterol transport. Some studies reported the association to be stronger in the presence of diabetes. The full length gene encoding SR-BI is comprised in 13 exons that are alternatively spliced to produce two major transcripts: the full length SR-BI and the splice variant SR-BII, in which exon 12 is skipped. Considering that type 2 diabetes status is characterized by changes in the concentration of plasma lipids, modifications in lipoprotein size and composition, which may be important modulators of the SR-BI expression;the aims of the study were to examine the influence of SR-BI polymorphism (rs838895) on lipid profile and SR-BI mRNA expression in a population of diabetic patients living in Juana Koslay City. Blood samples were drawn from controls (n = 40) and Type 2 diabetic patients (n = 66) and DNA and total RNA were obtained. SR-BI mRNA expression was measured by RT-PCR and SR-BI polymorphism was detected by Tetra Primer ARMSPCR. Compared to controls, diabetic patients had higher fasting serum glucose, glycated hemoglobin, triglycerides, total cholesterol, lowdensity lipoprotein cholesterol, and lower highdensity lipoprotein cholesterol. SR-BI mRNA expression was lower in T2DM when compared to controls, suggesting that the hyperglycemia presents in T2DM patients down-regulates SR-BI mRNA expression. Interestingly, we found that decreased SR-BI expression resulted in markedly increased plasma LDL concentrations in T2DM subjects, and the overexpression of SRBII isoform is responsible for the markedly increased plasma LDL-c concentrations. The polymorphism (rs838895) did not modify the mRNA level of SR-BI in leucocytes from control and diabetic patients. This study provides novel evidence suggesting that hyperglycemia may affect reverse cholesterol transport by controlling SRBI expression in diabetic patients. LDL cholesterol levels are associated with low SR-BI mRNA expression in T2DM.
