PMID- 11882518 OWN - NLM STAT- MEDLINE DCOM- 20020408 LR - 20131121 IS - 0193-1849 (Print) IS - 0193-1849 (Linking) VI - 282 IP - 4 DP - 2002 Apr TI - Shedding of TNF-alpha receptors, blood pressure, and insulin sensitivity in type 2 diabetes mellitus. PG - E952-9 AB - Tumor necrosis factor-alpha (TNF-alpha) is increasingly recognized as a key component in the development of insulin resistance and increased blood pressure. In a sample of 368 individuals, the ratio of soluble TNF-alpha receptors (sTNFR2/sTNFR1) correlated positively with systolic and diastolic blood pressure (P < 0.01). This ratio was significantly greater in type 2 diabetic subjects (DM-2) than in type 1 diabetic patients and was greater than in control nondiabetic subjects (P < 0.00001). The TNF-alpha receptor 1 (TNFR1) density in peripheral blood monocytes was similar in DM-2 patients and in nondiabetic subjects. After phorbol 12-myristate 13-acetate, TNFR1 shedding was significantly decreased in DM-2 compared with control subjects, and it was directly associated with insulin sensitivity (r = 0.54, P = 0.03). Serum sTNFR1 concentration was also linked to the vasodilatory response to glyceryltrinitrate (P = 0.01). Conversely, TNF-alpha receptor 2 shedding was negatively associated with insulin sensitivity (r = -0.54, P = 0.03), whereas shedding of L-selectin showed no significant association. After exercise-induced lowering of blood pressure, a parallel decrease in sTNFR2/sTNFR1 was observed in DM-2 patients. Our findings suggest that insulin resistance and blood pressure are linked to altered shedding of TNF-alpha receptors in DM-2. The latter seems reversible and is not genetically determined. FAU - Fernandez-Real, Jose-Manuel AU - Fernandez-Real JM AD - Unitat de Diabetologia, Endocrinologia i Nutricio, University Hospital of Girona, 17001 Girona, Spain. endocrino@htrueta.scs.es FAU - Lainez, Begona AU - Lainez B FAU - Vendrell, Joan AU - Vendrell J FAU - Rigla, Mercedes AU - Rigla M FAU - Castro, Antoni AU - Castro A FAU - Penarroja, Georgina AU - Penarroja G FAU - Broch, Montserrat AU - Broch M FAU - Perez, Antonio AU - Perez A FAU - Richart, Cristobal AU - Richart C FAU - Engel, Pablo AU - Engel P FAU - Ricart, Wifredo AU - Ricart W LA - eng PT - Journal Article PL - United States TA - Am J Physiol Endocrinol Metab JT - American journal of physiology. Endocrinology and metabolism JID - 100901226 RN - 0 (Antigens, CD) RN - 0 (Insulin) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Receptors, Tumor Necrosis Factor, Type I) RN - 0 (Receptors, Tumor Necrosis Factor, Type II) RN - G59M7S0WS3 (Nitroglycerin) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Adult MH - Aged MH - Antigens, CD/*blood MH - *Blood Pressure MH - Body Mass Index MH - Diabetes Mellitus, Type 1/physiopathology MH - Diabetes Mellitus, Type 2/*physiopathology MH - Female MH - Flow Cytometry MH - Humans MH - Insulin/*pharmacology MH - Insulin Resistance MH - Male MH - Middle Aged MH - Monocytes/chemistry MH - Nitroglycerin/pharmacology MH - Receptors, Tumor Necrosis Factor/*blood MH - Receptors, Tumor Necrosis Factor, Type I MH - Receptors, Tumor Necrosis Factor, Type II MH - Solubility MH - Tetradecanoylphorbol Acetate/pharmacology MH - Vasodilation/drug effects EDAT- 2002/03/08 10:00 MHDA- 2002/04/09 10:01 CRDT- 2002/03/08 10:00 PHST- 2002/03/08 10:00 [pubmed] PHST- 2002/04/09 10:01 [medline] PHST- 2002/03/08 10:00 [entrez] AID - 10.1152/ajpendo.00444.2001 [doi] PST - ppublish SO - Am J Physiol Endocrinol Metab. 2002 Apr;282(4):E952-9. doi: 10.1152/ajpendo.00444.2001.