Effect of different degrees of impaired glucose metabolism on the expression of inflammatory markers in monocytes of patients with atherosclerosis
Por:
Bernal-Lopez, MR, Llorente-Cortes, V, Calleja, F, Lopez-Carmona, D, Mayas, MD, Gomez-Huelgas, R, Badimon, L, Tinahones, FJ
Publicada:
1 ago 2013
Resumen:
Inflammatory markers are elevated in type 2 diabetic patients (DP) and may predict the development of type 2 diabetes. Our aims were to analyze differences in the expression of inflammatory and immunological molecules between DP and healthy subjects and to investigate whether glycemic control might prevent the overexpression of inflammatory markers in DP. Twenty-two DP with advanced atherosclerosis and eight healthy blood donors were included. DP were classified as well (HbA(1c) a parts per thousand currency sign 6.5) or poorly controlled (HbA(1c) > 6.5). In "in vitro" studies, monocytes were exposed to low (5.5 mM) or high glucose (26 mM) concentrations in the absence or presence of insulin. Expression profiling of 14 inflammatory genes was analyzed using TLDA analysis. "In vivo" results show that monocytes from DP had increased levels of monocyte chemoattractant protein (MCP-1) and interleukin 6 (IL6) and lower levels of Toll-like receptor 2 (TLR2) mRNA than healthy subjects. Well-controlled DP had lower levels of IL-6 than poorly controlled DP, suggesting that glycemic control may prevent IL6 mRNA alterations associated with diabetes. "In vitro" results demonstrate that glucose directly and significantly induced MCP-1 and IL6 and reduced TLR2 mRNA expression. Insulin at high dose (100 IU/ml) dramatically enhanced the upregulatory effects of glucose on MCP-1 and IL-6 and reduced per se TLR2 mRNA expression. MCP-1, IL-6 and TLR2 are key inflammatory players altered in monocytes from type 2 DP. Both hyperinsulinemia and hyperglycemia contribute to alter the expression of these genes. The glycemic control only significantly prevented IL6 overexpression in this group of patients.
Filiaciones:
Bernal-Lopez, MR:
Hosp Virgen de la Victoria, Dept Endocrinol, Biomed Res Lab, Malaga, Spain
Inst Salud Carlos III, Ciber Fisiopatol Obesidad & Nutr CB06 003, Madrid, Spain
Llorente-Cortes, V:
Hosp Santa Creu & Sant Pau, CSIC ICCC, Cardiovasc Res Ctr, Barcelona, Spain
Calleja, F:
Hosp Carlos Haya, Cardiovasc Surg Dept, Malaga, Spain
Lopez-Carmona, D:
Hosp Carlos Haya, Dept Internal Med, Malaga, Spain
Mayas, MD:
Hosp Virgen de la Victoria, Dept Endocrinol, Biomed Res Lab, Malaga, Spain
Gomez-Huelgas, R:
Inst Salud Carlos III, Ciber Fisiopatol Obesidad & Nutr CB06 003, Madrid, Spain
Hosp Carlos Haya, Dept Internal Med, Malaga, Spain
Badimon, L:
Inst Salud Carlos III, Ciber Fisiopatol Obesidad & Nutr CB06 003, Madrid, Spain
Hosp Santa Creu & Sant Pau, CSIC ICCC, Cardiovasc Res Ctr, Barcelona, Spain
Tinahones, FJ:
Hosp Virgen de la Victoria, Dept Endocrinol, Biomed Res Lab, Malaga, Spain
Inst Salud Carlos III, Ciber Fisiopatol Obesidad & Nutr CB06 003, Madrid, Spain
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