Marked impairment of protein tyrosine phosphatase 1B activity in adipose tissue of obese subjects with and without type 2 diabetes mellitus.
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.
Cheung
A
A
Department of Medicine, University of Tennessee College of Medicine, Memphis, USA.
Kusari
J
J
Jansen
D
D
Bandyopadhyay
D
D
Kusari
A
A
Bryer-Ash
M
M
D000273:Adipose Tissue / Q000201:enzymology*; D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D009765:Obesity / Q000201:enzymology*; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011233:Precipitin Tests; D017027:Protein Tyrosine Phosphatases / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5
D009419:Nerve Tissue Proteins; D010761:Phosphorus Radioisotopes; C516895:PTPRZ1 protein, human; D017027:Protein Tyrosine Phosphatases; C516897:Ptprz1 protein, rat; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5