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Increased energy expenditure, decreased adiposity, and tissue-specific insulin sensitivity in protein-tyrosine phosphatase 1B-deficient mice.

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.

Pubmed ID: 10891488


  • Klaman LD
  • Boss O
  • Peroni OD
  • Kim JK
  • Martino JL
  • Zabolotny JM
  • Moghal N
  • Lubkin M
  • Kim YB
  • Sharpe AH
  • Stricker-Krongrad A
  • Shulman GI
  • Neel BG
  • Kahn BB


Molecular and cellular biology

Publication Data

August 10, 2000

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI09815
  • Agency: NIDDK NIH HHS, Id: DK09903
  • Agency: NIDDK NIH HHS, Id: P01 DK 56116
  • Agency: NIDDK NIH HHS, Id: R01 DK040936

Mesh Terms

  • Adipose Tissue
  • Animals
  • Body Weight
  • Carrier Proteins
  • Energy Metabolism
  • Female
  • Glucose
  • Glucose Tolerance Test
  • Homeostasis
  • Hyperinsulinism
  • Insulin Resistance
  • Ion Channels
  • Leptin
  • Male
  • Membrane Proteins
  • Membrane Transport Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mitochondrial Proteins
  • Muscle, Skeletal
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Proteins
  • RNA, Messenger