title: Proximity to Delivery Alters Insulin Sensitivity and Glucose Metabolism in Pregnant Mice.
abstract: In late pregnancy, maternal insulin resistance occurs to support fetal growth, but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy at day 16 (D16) and near term at D19. Nonpregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by DEXA, tissue insulin signaling protein abundance by Western blotting, glucose tolerance and utilization, and insulin sensitivity using acute insulin administration and hyperinsulinemic-euglycemic clamps with [(3)H]glucose infusion. Whole-body insulin resistance occurred in D16 pregnant dams in association with basal hyperinsulinemia, insulin-resistant endogenous glucose production, and downregulation of several proteins in hepatic and skeletal muscle insulin signaling pathways relative to NP and D19 values. Insulin resistance was less pronounced at D19, with restoration of NP insulin concentrations, improved hepatic insulin sensitivity, and increased abundance of hepatic insulin signaling proteins. At D16, insulin resistance at whole-body, tissue, and molecular levels will favor fetal glucose acquisition, while improved D19 hepatic insulin sensitivity will conserve glucose for maternal use in anticipation of lactation. Tissue sensitivity to insulin, therefore, alters differentially with proximity to delivery in pregnant mice, with implications for human and other species.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, U.K.
authors.forename: Barbara
authors.initials: B
authors.lastname: Musial
authors.affiliation: University of Cambridge Metabolic Research Laboratories, MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K.
authors.forename: Denise S
authors.initials: DS
authors.lastname: Fernandez-Twinn
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, U.K.
authors.forename: Owen R
authors.initials: OR
authors.lastname: Vaughan
authors.affiliation: University of Cambridge Metabolic Research Laboratories, MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ozanne
authors.affiliation: University of Cambridge Metabolic Research Laboratories, MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K.
authors.forename: Peter
authors.initials: P
authors.lastname: Voshol
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, U.K.
authors.forename: Amanda N
authors.initials: AN
authors.lastname: Sferruzzi-Perri
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, U.K. alf100@cam.ac.uk.
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Fowden
mesh_terms: D000818:Animals; D036861:Delivery, Obstetric; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D036801:Parturition / Q000378:metabolism*; D011247:Pregnancy / Q000378:metabolism*; D013997:Time Factors
chemical_list: D005947:Glucose