Marked impairment of protein tyrosine phosphatase 1B activity in adipose tissue of obese subjects with and without type 2 diabetes mellitus

J Lab Clin Med. 1999 Aug;134(2):115-23. doi: 10.1016/s0022-2143(99)90115-4.


Protein tyrosine phosphatases (PTPs) are required for the dephosphorylation of the insulin receptor (IR) and its initial cellular substrates, and it has recently been reported that PTP-1B may play a role in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus (DM). We therefore determined the amount and activity of PTP-1B in abdominal adipose tissue obtained from lean nondiabetic subjects (lean control (LC)), obese nondiabetic subjects (obese control (OC)), and subjects with both type 2 DM (DM2) and obesity (obese diabetic (OD)). PTP-1B protein levels were 3-fold higher in OC than in LC (1444 +/- 195 U vs 500 +/- 146 U (mean +/- SEM), P < .015), while OD exhibited a 5.5-fold increase (2728 +/- 286 U, P < .01). PTP activity was assayed by measuring the dephosphorylating activity toward a phosphorus 32-labeled synthetic dodecapeptide. In contrast to the increased PTP-1B protein levels, PTP-1B activity per unit of PTP-1B protein was markedly reduced, by 71% and 88% in OC and OD, respectively. Non-PTP-1B tyrosine phosphatase activity was comparable in all three groups. Similar results were obtained when PTP-1B activity was measured against intact human IR. A significant correlation was found between body mass index (BMI) and PTP-1B level (r = 0.672, P < .02), whereas BMI and PTP-1B activity per unit of PTP-1B showed a strong inverse correlation (r = -0.801, P < .002). These data suggest that the insulin resistance of obesity and DM2 is characterized by the increased expression of a catalytically impaired PTP-1B in adipose tissue and that impaired PTP-1B activity may be pathogenic for insulin resistance in these conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipose Tissue / enzymology*
  • Adult
  • Aged
  • Animals
  • Blotting, Western
  • Cell Line
  • Diabetes Mellitus, Type 2 / enzymology*
  • Enzyme Activation / physiology
  • Female
  • Fibroblasts / cytology
  • Humans
  • Hydrolysis
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / metabolism*
  • Obesity / enzymology*
  • Phosphorus Radioisotopes
  • Phosphorylation
  • Precipitin Tests
  • Protein Tyrosine Phosphatases / analysis
  • Protein Tyrosine Phosphatases / metabolism*
  • Rats
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5


  • Nerve Tissue Proteins
  • Phosphorus Radioisotopes
  • PTPRZ1 protein, human
  • Protein Tyrosine Phosphatases
  • Ptprz1 protein, rat
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5