Islet-Sparing Effects of Protein Tyrosine Phosphatase-1b Deficiency Delays Onset of Diabetes in IRS2 Knockout Mice

Jake A. Kushner, Fawaz Haj, Lori D. Klaman, Matthew A. Dow, Barbara B. Kahn, Benjamin G. Neel, Morris F. White

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Protein tyrosine phosphatase-1b (Ptp1b) inhibits insulin and leptin signaling by dephosphorylating specific tyrosine residues in their activated receptor complexes. Insulin signals are mediated by tyrosine phosphorylation of the insulin receptor and its downstream targets, such as Irs1 and Irs2. Irs2 plays an especially important role in glucose homeostasis because it mediates some peripheral actions of insulin and promotes pancreatic β-cell function. To determine whether the deletion of Ptp1b compensates for the absence of Irs2, we analyzed mice deficient in both Ptp1b and Irs2. Pancreatic β-cell area decreased in Ptp1b-/- mice, consistent with decreased insulin requirements owing to increased peripheral insulin sensitivity. By contrast, peripheral insulin sensitivity and β-cell area increased in Irs2 -/-::Ptp1b-/- mice, which improved glucose tolerance in Irs2-/-::Ptp1b-/- mice and delayed diabetes until 3 months of age. However, β-cell function eventually failed to compensate for absence of Irs2. Our studies demonstrate a novel role for Ptp1b in regulating β-cell homeostasis and indicate that Ptp1b deficiency can partially compensate for lack of Irs2.

Original languageEnglish (US)
Pages (from-to)61-66
Number of pages6
JournalDiabetes
Volume53
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

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Non-Receptor Type 1 Protein Tyrosine Phosphatase
Knockout Mice
Insulin
Tyrosine
Insulin Resistance
Homeostasis
Glucose
Insulin Receptor
Leptin
Phosphorylation

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Islet-Sparing Effects of Protein Tyrosine Phosphatase-1b Deficiency Delays Onset of Diabetes in IRS2 Knockout Mice. / Kushner, Jake A.; Haj, Fawaz; Klaman, Lori D.; Dow, Matthew A.; Kahn, Barbara B.; Neel, Benjamin G.; White, Morris F.

In: Diabetes, Vol. 53, No. 1, 01.2004, p. 61-66.

Research output: Contribution to journalArticle

Kushner, Jake A. ; Haj, Fawaz ; Klaman, Lori D. ; Dow, Matthew A. ; Kahn, Barbara B. ; Neel, Benjamin G. ; White, Morris F. / Islet-Sparing Effects of Protein Tyrosine Phosphatase-1b Deficiency Delays Onset of Diabetes in IRS2 Knockout Mice. In: Diabetes. 2004 ; Vol. 53, No. 1. pp. 61-66.
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