Liver-specific protein-tyrosine phosphatase 1B (PTP1B) re-expression alters glucose homeostasis of PTP1B-/- mice

Fawaz Haj, Janice M. Zabolotny, Young Bum Kim, Barbara B. Kahn, Benjamin G. Neel

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

Protein-tyrosine phosphatase 1B (PTP1B) is an important negative regulator of insulin and leptin signaling in vivo. Mice lacking PTP1B (PTP1B-/- mice) are hyperresponsive to insulin and leptin and resistant to diet-induced obesity. The tissue(s) that mediate these effects of global PTP1B deficiency remain controversial. We exploited the high degree of hepatotropism of adenoviruses to assess the role of PTP1B in the liver. Liver-specific re-expression of PTP1B in PTP1B-/- mice led to marked attenuation of their enhanced insulin sensitivity. This correlated with, and was probably caused by, decreased insulin-stimulated tyrosyl phosphorylation of the insulin receptor (IR) and IR substrate 2-associated phosphatidylinositide 3-kinase activity. Analysis using phospho-specific antibodies for the IR revealed preferential dephosphorylation of Tyr-1162/1163 compared with Tyr-972 by PTP1B in vivo. Our findings show that the liver is a major site of the peripheral action of PTP1B in regulating glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)15038-15046
Number of pages9
JournalJournal of Biological Chemistry
Volume280
Issue number15
DOIs
StatePublished - Apr 15 2005
Externally publishedYes

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Non-Receptor Type 1 Protein Tyrosine Phosphatase
Liver
Homeostasis
Glucose
Insulin
Insulin Receptor
Leptin
Phospho-Specific Antibodies
Insulin Receptor Substrate Proteins
Phosphorylation
Nutrition
Adenoviridae
Insulin Resistance
Phosphotransferases
Obesity
Tissue
Diet

ASJC Scopus subject areas

  • Biochemistry

Cite this

Liver-specific protein-tyrosine phosphatase 1B (PTP1B) re-expression alters glucose homeostasis of PTP1B-/- mice. / Haj, Fawaz; Zabolotny, Janice M.; Kim, Young Bum; Kahn, Barbara B.; Neel, Benjamin G.

In: Journal of Biological Chemistry, Vol. 280, No. 15, 15.04.2005, p. 15038-15046.

Research output: Contribution to journalArticle

Haj, Fawaz ; Zabolotny, Janice M. ; Kim, Young Bum ; Kahn, Barbara B. ; Neel, Benjamin G. / Liver-specific protein-tyrosine phosphatase 1B (PTP1B) re-expression alters glucose homeostasis of PTP1B-/- mice. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 15. pp. 15038-15046.
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