BACKGROUND Diabetes is a progressive disease that increases glucose levels in the blood.While studies have shown that patients with pulmonary disease(both obstructive and restrictive pulmonary disease)have a higher pr...BACKGROUND Diabetes is a progressive disease that increases glucose levels in the blood.While studies have shown that patients with pulmonary disease(both obstructive and restrictive pulmonary disease)have a higher prevalence of type 2 diabetes mellitus(T2DM),there have been more studies on restrictive patterns than chronic obstructive pulmonary disease.AIM To assess whether restrictive and obstructive pulmonary diseases are associated with T2DM in Koreans.METHODS For our analysis,we used data from the Korea National Health and Nutrition Examination Survey.A total of 2830 subjects were included in this study.Spirometry results were categorized into three patterns:Normal,restrictive pulmonary disease(RPD),and obstructive pulmonary disease(OPD).RESULTS The factors used as diabetic indicators(i.e.homeostatic model assessment of insulin resistance,homeostatic model assessment of beta-cell function,glycated hemoglobin,and fasting insulin)were among the highest in RPD but not in OPD.Based on multivariate logistic regression analysis,subjects with RPD were found with an increased odds ratio[OR:1.907,95%confidence interval(CI):1.110-3.277]for T2DM compared with subjects with normal pulmonary function,whereas in patients with OPD,the OR had not increased.Model 4,which adjusted for the variables that could affect diabetes and pulmonary disease,showed a significant increase in the T2DM OR to RPD(OR:2.025,95%CI:1.264-3.244).On the other hand,no statistically significant difference was shown in OPD(OR:0.982,95%CI:0.634-1.519).CONCLUSION RPD,not OPD,is highly associated with T2DM regardless of the risk factors of various T2DMs that can be confounds.展开更多
4-1BB(CD137)is a strong enhancer of the proliferation of CD8^(+)T cells.Since these cells require increased production of energy and biomass to support their proliferation,we hypothesized that 4-1BB signaling activate...4-1BB(CD137)is a strong enhancer of the proliferation of CD8^(+)T cells.Since these cells require increased production of energy and biomass to support their proliferation,we hypothesized that 4-1BB signaling activated glucose and fatty acid metabolism.We found that treatment with agonistic anti-4-1BB mAb promoted the proliferation of CD8^(+)T cells in vitro,increasing their size and granularity.Studies with a glycolysis inhibitor and a fatty acid oxidation inhibitor revealed that CD8^(+)T cell proliferation required both glucose and fatty acid metabolism.Anti-4-1BB treatment increased glucose transporter 1 expression and activated the liver kinase B1(LKB1)-AMP-activated protein kinase(AMPK)-acetyl-CoA carboxylase(ACC)signaling pathway,which may be responsible for activating the metabolism of glucose and fatty acids.We also examined whether blocking glucose or fatty acid metabolism affected cell cycle progression and the anti-apoptotic effect of 4-1BB signaling.The increase of anti-apoptotic factors and cyclins in response to anti-4-1BB treatment was completely prevented by treating CD8^(+)T cells with the fatty acid oxidation inhibitor,etomoxir,but not with the glycolysis inhibitor,2-deoxy-D-glucose.We conclude that anti-4-1BB treatment activates glucose and fatty acid metabolism thus supporting the increased demand for energy and biomass,and that fatty acid metabolism plays a crucial role in enhancing the cell cycle progression of anti-CD3-activated CD8^(+)T cells in vitro and the anti-apoptotic effects of 4-1BB signaling on these cells.展开更多
文摘BACKGROUND Diabetes is a progressive disease that increases glucose levels in the blood.While studies have shown that patients with pulmonary disease(both obstructive and restrictive pulmonary disease)have a higher prevalence of type 2 diabetes mellitus(T2DM),there have been more studies on restrictive patterns than chronic obstructive pulmonary disease.AIM To assess whether restrictive and obstructive pulmonary diseases are associated with T2DM in Koreans.METHODS For our analysis,we used data from the Korea National Health and Nutrition Examination Survey.A total of 2830 subjects were included in this study.Spirometry results were categorized into three patterns:Normal,restrictive pulmonary disease(RPD),and obstructive pulmonary disease(OPD).RESULTS The factors used as diabetic indicators(i.e.homeostatic model assessment of insulin resistance,homeostatic model assessment of beta-cell function,glycated hemoglobin,and fasting insulin)were among the highest in RPD but not in OPD.Based on multivariate logistic regression analysis,subjects with RPD were found with an increased odds ratio[OR:1.907,95%confidence interval(CI):1.110-3.277]for T2DM compared with subjects with normal pulmonary function,whereas in patients with OPD,the OR had not increased.Model 4,which adjusted for the variables that could affect diabetes and pulmonary disease,showed a significant increase in the T2DM OR to RPD(OR:2.025,95%CI:1.264-3.244).On the other hand,no statistically significant difference was shown in OPD(OR:0.982,95%CI:0.634-1.519).CONCLUSION RPD,not OPD,is highly associated with T2DM regardless of the risk factors of various T2DMs that can be confounds.
基金funded by grants from the National Cancer Center of Korea(NCC-1310430)the National Research Foundation of Korea(NRF-2005-0093837,NRF-2013R1A1A2008703)+1 种基金the Korea Drug Development Fund(KDDF-201408-11)the Ministry of Trade,Industry and Energy of Korea(GLOBAL R&D PROJECT,N0000901).
文摘4-1BB(CD137)is a strong enhancer of the proliferation of CD8^(+)T cells.Since these cells require increased production of energy and biomass to support their proliferation,we hypothesized that 4-1BB signaling activated glucose and fatty acid metabolism.We found that treatment with agonistic anti-4-1BB mAb promoted the proliferation of CD8^(+)T cells in vitro,increasing their size and granularity.Studies with a glycolysis inhibitor and a fatty acid oxidation inhibitor revealed that CD8^(+)T cell proliferation required both glucose and fatty acid metabolism.Anti-4-1BB treatment increased glucose transporter 1 expression and activated the liver kinase B1(LKB1)-AMP-activated protein kinase(AMPK)-acetyl-CoA carboxylase(ACC)signaling pathway,which may be responsible for activating the metabolism of glucose and fatty acids.We also examined whether blocking glucose or fatty acid metabolism affected cell cycle progression and the anti-apoptotic effect of 4-1BB signaling.The increase of anti-apoptotic factors and cyclins in response to anti-4-1BB treatment was completely prevented by treating CD8^(+)T cells with the fatty acid oxidation inhibitor,etomoxir,but not with the glycolysis inhibitor,2-deoxy-D-glucose.We conclude that anti-4-1BB treatment activates glucose and fatty acid metabolism thus supporting the increased demand for energy and biomass,and that fatty acid metabolism plays a crucial role in enhancing the cell cycle progression of anti-CD3-activated CD8^(+)T cells in vitro and the anti-apoptotic effects of 4-1BB signaling on these cells.
