title: Adipose Tissue Insulin Resistance in Gestational Diabetes.
abstract: Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance (IR) and altered glucose-lipid metabolism. We propose that ectonucleotide pyrophosphate phosphodiesterase-1 (ENPP1), a protein known to induce adipocyte IR, is a determinant of GDM. Our objective was to study ENPP1 expression in adipose tissue (AT) of obese pregnant women with or without GDM, as well as glucose tolerance in pregnant transgenic (Tg) mice with AT-specific overexpression of human ENPP1.
  
  
  
  AT biopsies and blood were collected from body mass index-matched obese pregnant women non-GDM (n = 6), GDM (n = 7), and nonpregnant controls (n = 6) undergoing cesarian section or elective surgeries, respectively. We measured the following: (1) Expression of key molecules involved in insulin signaling and glucose-lipid metabolism in AT; (2) Plasma glucose and insulin levels and calculation of homeostasis model assessment of IR (HOMA-IR); (3) Intraperitoneal glucose tolerance test in AtENPP1 Tg pregnant mice.
  
  
  
  We found that: (1) Obese GDM patients have higher AT ENPP1 expression than obese non-GDM patients, or controls (P = 0.01-ANOVA). (2) ENPP1 expression level correlated negatively with glucose transporter 4 (GLUT4) and positively with insulin receptor substrate-1 (IRS-1) serine phosphorylation, and to other adipocyte functional proteins involved in glucose and lipid metabolism (P < 0.05 each), (3) AT ENPP1 expression levels were positively correlated with HOMA-IR (P = 0.01-ANOVA). (4) Pregnant AT ENPP1 Tg mice showed higher plasma glucose than wild type animals (P = 0.046-t test on area under curve [AUC]glucose).
  
  
  
  Our results provide evidence of a causative link between ENPP1 and alterations in insulin signaling, glucose uptake, and lipid metabolism in subcutaneous abdominal AT of GDM, which may mediate IR and hyperglycemia in GDM.
authors.affiliation: 1 Division of Endocrinology, Department of Internal Medicine, University of Texas Medical Branch , Galveston, Texas.
authors.forename: Batbayar
authors.initials: B
authors.lastname: Tumurbaatar
authors.affiliation: 2 Department of Obstetrics and Gynecology, Maternal and Fetal Medicine, University of Texas Medical Branch , Galveston, Texas.
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Poole
authors.affiliation: 2 Department of Obstetrics and Gynecology, Maternal and Fetal Medicine, University of Texas Medical Branch , Galveston, Texas.
authors.forename: Gayle
authors.initials: G
authors.lastname: Olson
authors.affiliation: 2 Department of Obstetrics and Gynecology, Maternal and Fetal Medicine, University of Texas Medical Branch , Galveston, Texas.
authors.forename: Michel
authors.initials: M
authors.lastname: Makhlouf
authors.affiliation: 1 Division of Endocrinology, Department of Internal Medicine, University of Texas Medical Branch , Galveston, Texas.
authors.forename: Hanaa S
authors.initials: HS
authors.lastname: Sallam
authors.affiliation: 1 Division of Endocrinology, Department of Internal Medicine, University of Texas Medical Branch , Galveston, Texas.
authors.forename: Shwetha
authors.initials: S
authors.lastname: Thukuntla
authors.affiliation: 1 Division of Endocrinology, Department of Internal Medicine, University of Texas Medical Branch , Galveston, Texas.
authors.forename: Sucharitha
authors.initials: S
authors.lastname: Kankanala
authors.affiliation: 3 Department of General Surgery, University of Texas Medical Branch , Galveston, Texas.
authors.forename: Obos
authors.initials: O
authors.lastname: Ekhaese
authors.affiliation: 3 Department of General Surgery, University of Texas Medical Branch , Galveston, Texas.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Gomez
authors.affiliation: 4 Bay Area Metabolic Health, Houston, Texas.
authors.forename: Manisha
authors.initials: M
authors.lastname: Chandalia
authors.affiliation: 1 Division of Endocrinology, Department of Internal Medicine, University of Texas Medical Branch , Galveston, Texas.
authors.forename: Nicola
authors.initials: N
authors.lastname: Abate
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D016640:Diabetes, Gestational / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D011755:Pyrophosphatases / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases
keywords: ENPP1; gestational diabetes; insulin signaling; pregnancy