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Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene.

Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin tolerance tests. The PTP-1B-/- mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B-/- and PTP-1B+/- mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+ mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity.

Pubmed ID: 10066179


  • Elchebly M
  • Payette P
  • Michaliszyn E
  • Cromlish W
  • Collins S
  • Loy AL
  • Normandin D
  • Cheng A
  • Himms-Hagen J
  • Chan CC
  • Ramachandran C
  • Gresser MJ
  • Tremblay ML
  • Kennedy BP


Science (New York, N.Y.)

Publication Data

March 5, 1999

Associated Grants


Mesh Terms

  • Animals
  • Blood Glucose
  • Diabetes Mellitus, Type 2
  • Dietary Fats
  • Gene Targeting
  • Glucose Tolerance Test
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Insulin Resistance
  • Liver
  • Male
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal
  • Obesity
  • Phosphoproteins
  • Phosphorylation
  • Phosphotyrosine
  • Protein Tyrosine Phosphatases
  • Receptor, Insulin
  • Signal Transduction