PTP1B deficiency enhances liver growth during suckling by increasing the expression of insulin-like growth factor-I

✍ Scribed by Fernando Escrivá; Águeda González-Rodriguez; Elisa Fernández-Millán; Cristina M. Rondinone; Carmen Álvarez; Ángela M. Valverde

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 342 KB
• Volume: 225
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.22246

✦ Synopsis

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.