Shedding of TNF-alpha receptors, blood pressure, and insulin sensitivity in type 2 diabetes mellitus

Am J Physiol Endocrinol Metab. 2002 Apr;282(4):E952-9. doi: 10.1152/ajpendo.00444.2001.


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.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / blood*
  • Blood Pressure*
  • Body Mass Index
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Female
  • Flow Cytometry
  • Humans
  • Insulin / pharmacology*
  • Insulin Resistance
  • Male
  • Middle Aged
  • Monocytes / chemistry
  • Nitroglycerin / pharmacology
  • Receptors, Tumor Necrosis Factor / blood*
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Solubility
  • Tetradecanoylphorbol Acetate / pharmacology
  • Vasodilation / drug effects


  • Antigens, CD
  • Insulin
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Nitroglycerin
  • Tetradecanoylphorbol Acetate