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- Title
PTP1B deficiency enhances liver growth during suckling by increasing the expression of insulin-like growth factor-I.
- Authors
ESCRIVÁ, FERNANDO; GONZÁLEZ-RODRIGUEZ, ÁGUEDA; FERNÁNDEZ-MILLÁN, ELISA; RONDINONE, CRISTINA M.; ÁLVAREZ, CARMEN; VALVERDE, ÁNGELA M.
- Abstract
Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin and tyrosine kinase growth factor signaling. We have recently demonstrated that PTP1B deficiency increases GLUT2/insulin receptor (IR) A complexes and glucose uptake in suckling, but not adult, primary hepatocytes. Herein we have investigated intrahepatic glucose utilization in 3–5 days old wild-type and PTP1B-/- mice. PTP1B deficiency decreased glycogen, lactate, and pyruvate content in the livers from suckling mice. Conversely, the activity of glucose 6-phosphate dehydrogenase (G6PD), the rate limiting enzyme of the pentose phosphate cycle (PPC) which provides substrates for DNA synthesis, was enhanced in the liver of PTP1B-/- animals. Liver weight, liver-to-body mass ratio, DNA content, and PCNA expression were increased in PTP1B-/- suckling mice compared to the wild-type controls. At the molecular level, STAT 5B phosphorylation, IGF-I mRNA, and protein levels as well as IGF-IR tyrosine phosphorylation were increased in the livers of PTP1B-deficient neonates. Unexpectedly, hepatic and serum triglycerides (TG) were increased by PTP1B deficiency, although the expression of lipogenic enzymes remained as in the wild-type controls. However, the analysis of milk composition revealed higher TG content in lactating females lacking PTP1B. The effects of PTP1B deficiency on G6PD activity, STAT 5B/IGF-I/IGF-IR axis, PCNA expression and liver growth during suckling were maintained by transferring PTP1B-/- embryos (PTP1B-/-T) to a wild-type female. Conversely, PTP1B-/-T mice did not show hepatic fat accumulation. In conclusion, the present study suggests that PTP1B plays a unique role in the control of the physiological liver development after birth. J. Cell. Physiol. 225: 214–222, 2010. © 2010 Wiley-Liss, Inc.
- Subjects
PROTEIN-tyrosine phosphatase; INSULIN-like growth factor-binding proteins; LIVER cells; MICE; ENZYMES
- Publication
Journal of Cellular Physiology, 2010, Vol 225, Issue 1, p214
- ISSN
0021-9541
- Publication type
Article
- DOI
10.1002/jcp.22246