IRS2 and PTP1B: Two opposite modulators of hepatic insulin signalling

Abstract

Type 2 Diabetes mellitus (T2D) is the most common endocrine disorder associated to metabolic syndrome (MS) and occurs when insulin secretion can no compensate peripheral insulin resistance. Among peripheral tissues, the liver controls glucose homeostasis due to its ability to consume and produce glucose. The molecular mechanism underlying hepatic insulin resistance is not completely understood; however, it involves the impairment of the insulin signalling network. Among the critical nodes of hepatic insulin signalling, insulin receptor substrate 2 (IRS2) and protein tyrosine phosphatase 1B (PTP1B) modulate the phosphatidylinositol (PI) 3-kinase/Akt/Foxo1 pathway that controls the suppression of gluconeogenic genes. In this review, we will focus on recent findings regarding the molecular mechanism by which IRS2 and PTP1B elicit opposite effects on carbohydrate metabolism in the liver in response to insulin. Finally, we will discuss the involvement of the critical nodes of insulin signalling in non-alcoholic fatty liver disease (NAFLD) in humans.

Key words::

• insulin
• type 2 diabetes
• IRS2
• PTP1B
• hepatocytes
• gluconeogenic enzymes
• apoptosis
• NAFLD

Acknowledgements

This work was supported by grants from Ministerio de Ciencia e Innovación (Spain) BFU2005-01615, BFU2008-02420, SAF2009-08114 and CIT-090100-2007-35 from Ministerio de Ciencia e Innovación (MCINN, Spain) and Centro de Investigación Biomedica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) (Instituto Salud Carlos III, MICINN, Spain). We would like to thank to all of our collaborators for their continuous support. A.G-R. holds a postdoctoral contract from CIBERDEM.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.