title: PTP1B deficiency enhances liver growth during suckling by increasing the expression of insulin-like growth factor-I.
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.
authors.affiliation: Centro de Investigación Biomédica en Red de Diabetes y Enferemdades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Escrivá
authors.forename: Agueda
authors.initials: A
authors.lastname: González-Rodriguez
authors.forename: Elisa
authors.initials: E
authors.lastname: Fernández-Millán
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Rondinone
authors.forename: Carmen
authors.initials: C
authors.lastname: Alvarez
authors.forename: Angela M
authors.initials: AM
authors.lastname: Valverde
mesh_terms: D000818:Animals; D000833:Animals, Suckling; D005260:Female; D005947:Glucose / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007774:Lactation / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000172:deficiency* / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D050799:STAT5 Transcription Factor; C494096:Stat5b protein, mouse; D014280:Triglycerides; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D005947:Glucose