title: 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.
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols (CSIC/UAM), C/Arturo Duperier 4, 28029 Madrid, Spain. avalverde@iib.uam.es
authors.forename: Angela M
authors.initials: AM
authors.lastname: Valverde
authors.forename: Agueda
authors.initials: A
authors.lastname: González-Rodríguez
mesh_terms: D000818:Animals; D050260:Carbohydrate Metabolism; D005234:Fatty Liver / Q000503:physiopathology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005943:Gluconeogenesis / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D051858:Forkhead Transcription Factors; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D005947:Glucose