Hepatic IRS1 and ß-catenin expression is associated with histological progression and overt diabetes emergence in NAFLD patients

Journal of Gastroenterology
Kenichiro EnookuKazuhiko Koike

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes. Our aim was to investigate the relationship between NAFLD and impaired glucose metabolism in terms of insulin receptor substrate 1 and 2 (IRS1 and IRS2) expression in the liver. Liver biopsy was performed at the University of Tokyo Hospital between November 2011 and March 2016 on 146 patients with NAFLD who were not being treated with any diabetes or dyslipidemia drugs. Among them, 63 underwent liver biopsy after an overnight fast, and 83 at 5 h after an oral glucose tolerance test (OGTT). Differences in messenger RNA (mRNA) levels of several glucose metabolism-related factors were determined and correlated with hepatic histological changes assessed by NAFLD activity score. We prospectively followed up with the patients until May 2017. Hepatic necroinflammation was significantly correlated with serum insulin levels and inversely correlated with IRS1 mRNA levels. In specimens obtained after an OGTT, hepatic necroinflammation and IRS1 expression correlated significantly with both peripheral and hepatic insulin resistance. We also found that hepatic β-catenin and glucokinase mRNA levels were elevated in patients undergoing liver biopsy after an OGTT, es...Continue Reading

References

Jul 1, 1997·The Journal of General Virology·K MoriyaK Koike
May 29, 1999·Gastroenterology·C A MatteoniA J McCullough
Nov 24, 1999·The American Journal of Medicine·G MarchesiniN Melchionda
May 26, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·David E KleinerUNKNOWN Nonalcoholic Steatohepatitis Clinical Research Network
Feb 8, 2006·Annual Review of Physiology·Sudha B Biddinger, C Ronald Kahn
Dec 1, 2006·The New England Journal of Medicine·Renata BelfortKenneth Cusi
Dec 29, 2006·Diabetes Care·Muhammad A Abdul-GhaniRalph A DeFronzo
Oct 22, 2009·The Journal of Biological Chemistry·Guido T BommerEric R Fearon
Apr 8, 2010·Current Pharmaceutical Design·E BugianesiG Marchesini
Jun 10, 2010·BMC Gastroenterology·Beverley BalkauUNKNOWN Group Study D.E.S.I.R
Jun 29, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xu-Feng ZhangSatdarshan P S Monga
Jul 17, 2010·Genes & Development·John C YoonStephen J Elledge
Mar 8, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Silvia Sookoian, Carlos J Pirola
Mar 25, 2011·Current Diabetes Reports·Guido LattuadaGianluca Perseghin
Dec 21, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Romina LomonacoKenneth Cusi
Jan 11, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Carmen Berasain, Matías A Avila
Oct 11, 2014·The American Journal of Pathology·Jaideep BehariQing Liu
Mar 10, 2015·Gastroenterology·Satdarshan Pal Monga
Apr 24, 2015·Alcoholism, Clinical and Experimental Research·Chelsea Q XuMiran Kim
Aug 2, 2016·JAMA Pediatrics·Kimberly P NewtonUNKNOWN Nonalcoholic Steatohepatitis Clinical Research Network
Dec 17, 2016·Diabetes Care·UNKNOWN American Diabetes Association
Jul 16, 2017·Scientific Reports·Yoshitaka SakuraiTakashi Kadowaki

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Citations

Mar 14, 2019·The American Journal of Gastroenterology·Oyuntugs ByambasukhEva Corpeleijn
Dec 7, 2018·Acta Diabetologica·Amedeo LonardoMauro Maurantonio
Jun 4, 2020·International Journal of Molecular Sciences·Hideki Fujii Japan Study Group Of Nafld Jsg-Nafld
Mar 1, 2019·Nature Communications·Takayoshi SasakoKohjiro Ueki
Dec 29, 2020·Frontiers in Pediatrics·Yu-Cheng LinYen-Hsuan Ni
Feb 8, 2021·Computers in Biology and Medicine·Athina I Amanatidou, George V Dedoussis
May 1, 2021·International Journal of Molecular Sciences·Yoshitaka SakuraiTakashi Kadowaki
Jul 16, 2021·European Journal of Pharmacology·Rana K El-AsfarHala O El-Mesallamy
Sep 24, 2021·Biomarkers in Medicine·Hussein K Al-HakeimMichael Maes
Oct 1, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jie-Lei ZhangYan-Zhou Zhang

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Methods Mentioned

BETA
biopsy
PCR
biopsies
transgenic
ubiquitination

Software Mentioned

PLUS

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