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

Mol Cell Biol. 2000 Aug;20(15):5479-89. doi: 10.1128/mcb.20.15.5479-5489.2000.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipose Tissue / physiology*
  • Animals
  • Body Weight / genetics
  • Carrier Proteins / genetics
  • Energy Metabolism*
  • Female
  • Glucose / metabolism
  • Glucose Tolerance Test
  • Homeostasis
  • Hyperinsulinism / metabolism
  • Insulin Resistance / genetics*
  • Ion Channels
  • Leptin / genetics
  • Male
  • Membrane Proteins / genetics
  • Membrane Transport Proteins*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mitochondrial Proteins*
  • Muscle, Skeletal / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases / deficiency*
  • Protein Tyrosine Phosphatases / genetics
  • Proteins / genetics
  • RNA, Messenger
  • Uncoupling Protein 1
  • Uncoupling Protein 2
  • Uncoupling Protein 3

Substances

  • Carrier Proteins
  • Ion Channels
  • Leptin
  • Membrane Proteins
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Proteins
  • RNA, Messenger
  • Uncoupling Protein 1
  • Uncoupling Protein 2
  • Uncoupling Protein 3
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatases
  • Ptpn1 protein, mouse
  • Glucose