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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 RIS Download

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 | Uncoupling Protein 1 | Uncoupling Protein 2 | Uncoupling Protein 3

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Associated grants

  • Agency: NIDDK NIH HHS, Id: F32 DK009903
  • Agency: NIAID NIH HHS, Id: AI09815
  • Agency: NIDDK NIH HHS, Id: R01 DK040936
  • Agency: NIDDK NIH HHS, Id: P30 DK046200
  • Agency: NIDDK NIH HHS, Id: P30 DK045735
  • Agency: NIDDK NIH HHS, Id: P01 DK 56116
  • Agency: NCI NIH HHS, Id: R01 CA049152
  • Agency: NIDDK NIH HHS, Id: P01 DK056116
  • Agency: NIDDK NIH HHS, Id: R01 DK043051
  • Agency: NIDDK NIH HHS, Id: P01 DK050654
  • Agency: NIDDK NIH HHS, Id: DK09903
  • Agency: NIAID NIH HHS, Id: F32 AI009815

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