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

Abstract

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.

• Authors: A Cheung, J Kusari, D Jansen, D Bandyopadhyay, A Kusari, M Bryer-Ash
• Journal: The Journal of laboratory and clinical medicine (J Lab Clin Med) Vol. 134 Issue 2 Pg. 115-23 (Aug 1999) ISSN: 0022-2143 [Print] United States
• PMID: 10444024 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• 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, metabolism)
• Obesity (enzymology)
• Phosphorus Radioisotopes
• Phosphorylation
• Precipitin Tests
• Protein Tyrosine Phosphatases (analysis, metabolism)
• Rats
• Receptor-Like Protein Tyrosine Phosphatases, Class 5