title: Liver ENPP1 protein increases with remission of type 2 diabetes after gastric bypass surgery.
abstract: BACKGROUND
  Type 2 diabetes mellitus (T2DM) is a progressive disease resulting from increasing insulin resistance and reduced pancreatic β-cell insulin secretion. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) inhibits insulin signalling and may contribute to the pathogenesis of T2DM. Others have found elevated ENPP1 levels in muscle, fat, and skin tissues from insulin resistant individuals, but similar data on liver ENPP1 is lacking. The purpose of this study was to compare expression and protein concentrations of ENPP1 in liver between patients with and without T2DM.
  
  
  METHODS
  Roux-en-Y gastric bypass surgery (RYGB) results in remission of insulin resistance and T2DM thus presenting an opportunity to examine some critical aspects of these conditions. We measured liver ENPP1 gene and protein expression in individuals with or without T2DM at RYGB and on average 17 (±5.6) months later.
  
  
  RESULTS
  We found liver ENPP1 protein abundance was lower in individuals with T2DM than in those with normal glucose tolerance, and increased after RYGB surgery in those individuals who had remission of T2DM. ENPP1 positively correlated with insulin sensitivity at the liver (as measured by HOMA-IR), which is contrary to what others have reported in other insulin target tissues.
  
  
  CONCLUSIONS
  Liver ENPP1 expression in T2DM is the reverse of that expected based on expression in other tissues and is likely due to the unique role the liver has in insulin clearance. The work presented here adds another dimension to the role of ENPP1, and supports the hypothesis that ENPP1 may act as a natural modulator of insulin signalling in the liver.
authors.affiliation: Wakefield Biomedical Research Unit, Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand. vinko.besic@otago.ac.nz.
authors.forename: Vinko
authors.initials: V
authors.lastname: Besic
authors.affiliation: Wakefield Biomedical Research Unit, Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand. richards@p3research.co.nz.|The Wakefield Clinic, Wakefield Hospital, Wellington, New Zealand. richards@p3research.co.nz.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Stubbs
authors.affiliation: Wakefield Biomedical Research Unit, Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand. mark.hayes@anu.edu.au.|The John Curtin School of Medical Research, The Australian National University, Canberra, Australia. mark.hayes@anu.edu.au.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Hayes
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D015390:Gastric Bypass; D015870:Gene Expression; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D009767:Obesity, Morbid / Q000150:complications / Q000378:metabolism / Q000601:surgery; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism*; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism*; D012074:Remission Induction
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases