Cited by 2,210Protein Tyrosine PhosphatasesAdipokines, Inflammation, and Metabolic DiseasesMetabolism, Diabetes, and Cancer

Increased Insulin Sensitivity and Obesity Resistance in Mice Lacking the Protein Tyrosine Phosphatase-1B Gene

Elchebly, Mounib, Payette, Paul, Michaliszyn, Eva, Cromlish, Wanda, Collins, Susan, Loy, Ailsa Lee, Normandin, Denis, Cheng, Alan +6 more·1999·Science

Abstract

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.

Integrity signals

Registry

Crossref · 10.1126/science.283.5407.1544

Cites

19 of 19 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • PTP1B inhibits leptin and insulin signaling in cultured cells and in vivo via dephosphorylation of Jak2.

    “the protein tyrosine phosphatase (PTP)1B inhibits leptin and insulin signaling in cultured cells and in vivo via dephosphorylation of Jak2 (48, 93).”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Elchebly, M., Payette, P., Michaliszyn, E., Cromlish, W., Collins, S., Loy, A. L., Normandin, D., Cheng, A., Himms-Hagen, J., Chan, C.-C., Ramachandran, C., Gresser, M. J., Tremblay, M. L., & Kennedy, B. P.
Affiliations
  • McGill University (CA)
  • Merck Canada Inc. (Canada) (CA)
  • Department of Biochemistry, McGill University, 3655 Drummond Street, Montreal, Quebec, Canada, H3G 1Y6.
  • Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada, K1H 8M5.
Corresponding author
Kennedy, Brian P.
Venue
Science
Published
1999-03-05
Volume
283
Issue
5407
Pages
1544-1548
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2123229219
Cited by
2,210
References
19
Citations by year
2026: 36 · 2025: 32 · 2024: 49 · 2023: 51 · 2022: 41 · 2021: 56 · 2020: 60 · 2019: 64 · 2018: 62 · 2017: 87 · 2016: 84 · 2015: 91 · 2014: 99 · 2013: 112 · 2012: 133
FWCI
28.35
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
PTP1B, insulin sensitivity, insulin resistance, obesity, insulin signaling, insulin receptor phosphorylation, glucose tolerance, high-fat diet, type 2 diabetes, knockout mice, fuel metabolism
MeSH terms
Animals, Blood Glucose, Diabetes Mellitus, Type 2, Dietary Fats, Glucose Tolerance Test, Insulin, Insulin Resistance, Liver, Male, Obesity, Phosphoproteins, Phosphorylation, Receptor, Insulin, Signal Transduction, Protein Tyrosine Phosphatases, Mice, Knockout, Gene Targeting, Muscle, Skeletal, Phosphotyrosine, Mice, Insulin Receptor Substrate Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review