Shedding of TNF-alpha receptors, blood pressure, and insulin sensitivity in type 2 diabetes mellitus.
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.
Fernandez-Real
José-Manuel
JM
Unitat de Diabetologia, Endocrinologia i Nutricio, University Hospital of Girona, 17001 Girona, Spain. endocrino@htrueta.scs.es
Lainez
Begoña
B
Vendrell
Joan
J
Rigla
Mercedes
M
Castro
Antoni
A
Peñarroja
Georgina
G
Broch
Montserrat
M
Pérez
Antonio
A
Richart
Cristobal
C
Engel
Pablo
P
Ricart
Wifredo
W
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood*; D001794:Blood Pressure; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry; D005996:Nitroglycerin / Q000494:pharmacology; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012995:Solubility; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D015703:Antigens, CD; D007328:Insulin; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D005996:Nitroglycerin; D013755:Tetradecanoylphorbol Acetate