Increased Energy Expenditure, Decreased Adiposity, and Tissue-Specific Insulin Sensitivity in Protein-Tyrosine Phosphatase 1B-Deficient Mice
Open accessAbstract
Protein-tyrosine phosphatase 1B (PTP-1B) is a major protein-tyrosine phosphatase that has been implicated in the regulation of insulin action, as well as in other signal transduction pathways. To investigate the role of PTP-1B in vivo, we generated homozygotic PTP-1B-null mice by targeted gene disruption. PTP-1B-deficient mice have remarkably low adiposity and are protected from diet-induced obesity. Decreased adiposity is due to a marked reduction in fat cell mass without a decrease in adipocyte number. Leanness in PTP-1B-deficient mice is accompanied by increased basal metabolic rate and total energy expenditure, without marked alteration of uncoupling protein mRNA expression. In addition, insulin-stimulated whole-body glucose disposal is enhanced significantly in PTP-1B-deficient animals, as shown by hyperinsulinemic-euglycemic clamp studies. Remarkably, increased insulin sensitivity in PTP-1B-deficient mice is tissue specific, as insulin-stimulated glucose uptake is elevated in skeletal muscle, whereas adipose tissue is unaffected. Our results identify PTP-1B as a major regulator of energy balance, insulin sensitivity, and body fat stores in vivo.
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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).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [93]
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References 78 · Cited by 1,235
- Authors
- Klaman, L. D., Boss, O., Peroni, O. D., Kim, J. K., Martino, J. L., Zabolotny, J. M., Moghal, N., Lubkin, M., Kim, Y.-B., Sharpe, A. H., Stricker-Krongrad, A., Shulman, G. I., Neel, B. G., & Kahn, B. B.
- Affiliations
- Cancer Biology Program, Division of Hematology-Oncology
- Beth Israel Deaconess Medical Center (US)
- Howard Hughes Medical Institute (US)
- Takeda Oncology (United States) (US)
- Brigham and Women's Hospital (US)
- Metabolic Diseases Physiology, Millennium Pharmaceuticals, Cambridge, Massachusetts 02139
- Corresponding author
- Neel, Benjamin G.
- Kahn, Barbara B.
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-08-01
- Volume
- 20
- Issue
- 15
- Pages
- 5479-5489
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC85999
- OpenAlex
- W2115681043
- Cited by
- 1,235
- References
- 78
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 20 · 2023: 24 · 2022: 23 · 2021: 34 · 2020: 32 · 2019: 46 · 2018: 45 · 2017: 59 · 2016: 43 · 2015: 45 · 2014: 56 · 2013: 70 · 2012: 72
- FWCI
- 17.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (DK46200, CA49152, DK-45735)
- National Cancer Institute (R01CA049152)
- National Institute of Allergy and Infectious Diseases (F32AI009815, AI09815)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01DK56116, F32DK009903, DK09903, P01DK056116, P30DK046200, R01DK040936, P01DK050654, R01DK043051, P30DK045735)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- PTP1B, insulin sensitivity, energy expenditure, adiposity, diet-induced obesity, basal metabolic rate, uncoupling proteins, glucose disposal, skeletal muscle glucose uptake, adipose tissue, energy balance, body fat stores
- MeSH terms
- Uncoupling Protein 2, Uncoupling Protein 3, Uncoupling Protein 1, Adipose Tissue, Animals, Body Weight, Carrier Proteins, Energy Metabolism, Female, Glucose, Glucose Tolerance Test, Homeostasis, Hyperinsulinism, Insulin Resistance, Ion Channels, Male, Membrane Proteins, Mice, Inbred C57BL, Mice, Mutant Strains, Proteins, RNA, Messenger, Protein Tyrosine Phosphatases, Muscle, Skeletal, Leptin, Mitochondrial Proteins, Membrane Transport Proteins, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 1
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