HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/G338    most recent 00514.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by González-Rodriguez, A. Articles by Valverde, A. M. PubMed PubMed Citation Articles by González-Rodriguez, A. Articles by Valverde, A. M.

HORMONES AND SIGNALING

PTP1B deficiency increases glucose uptake in neonatal hepatocytes: involvement of IRA/GLUT2 complexes

¹Instituto de Investigaciones Biomédicas Alberto Sols (Consejo Superior de Investigaciones Cientificas/Universidad Autonoma de Madrid), Madrid, Spain; ²Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabólicas Asociadas. Instituto de Salud Carlos III, Spain; ³Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University, Madrid, Spain; ⁴Department of Experimental and Clinical Medicine, University Magna Græcia of Catanzaro, Catanzaro, Italy; and ⁵Metabolic Diseases Research, Global Pharmaceutical Research Division, Abbott Laboratories, Abbott Park, Illinois

Submitted 8 November 2007 ; accepted in final form 3 June 2008

The contribution of the liver to glucose utilization is essential to maintain glucose homeostasis. Previous data from protein tyrosine phosphatase (PTP) 1B-deficient mice demonstrated that the liver is a major site for PTP1B action in the periphery. In this study, we have investigated the consequences of PTP1B deficiency in glucose uptake in hepatocytes from neonatal and adult mice. The lack of PTP1B increased basal glucose uptake in hepatocytes from neonatal (3–5 days old) but not adult (10–12 wk old) mice. This occurs without changes in hexokinase, glucokinase, and glucose 6-phosphatase enzymatic activities. By contrast, the glucose transporter GLUT2 was upregulated at the protein level in neonatal hepatocytes and livers from PTP1B-deficient neonates. These results were accompanied by a significant increase in the net free intrahepatic glucose levels in the livers of PTP1B^–/– neonates. The association between GLUT2 and insulin receptor (IR) A isoform was increased in PTP1B^–/– neonatal hepatocytes compared with the wild-type. Indeed, PTP1B deficiency in neonatal hepatocytes shifted the ratio of isoforms A and B of the IR by increasing the amount of IRA and decreasing IRB. Moreover, overexpression of IRA in PTP1B^–/– neonatal hepatocytes increased the amount of IRA/GLUT2 complexes. Conversely, hepatocytes from adult mice only expressed IRB. Since IRA plays a direct role in the regulation of glucose uptake in neonatal hepatocytes through its specific association with GLUT2, we propose the increase in IRA/GLUT2 complexes due to PTP1B deficiency as the molecular mechanism of the increased glucose uptake in the neonatal stage.

liver; insulin receptor isoforms; glucose transport; insulin sensitivity