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Proximity to Delivery Alters Insulin Sensitivity and Glucose Metabolism in Pregnant Mice.

Accepted version
Peer-reviewed

Repository DOI


Type

Article

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Authors

Musial, Barbara 
Fernandez-Twinn, Denise S 
Vaughan, Owen R 
Ozanne, Susan E 
Voshol, Peter 

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.

Description

Keywords

Animals, Delivery, Obstetric, Female, Glucose, Insulin Resistance, Lipid Metabolism, Male, Mice, Mice, Inbred C57BL, Parturition, Pregnancy, Time Factors

Journal Title

Diabetes

Conference Name

Journal ISSN

0012-1797
1939-327X

Volume Title

65

Publisher

American Diabetes Association
Sponsorship
Medical Research Council (MC_UU_12012/4)
Medical Research Council (MC_UU_12012/5/B)
Medical Research Council (G0600717)
Medical Research Council (MC_UU_12012/5)
British Heart Foundation (None)
Medical Research Council (MC_PC_12012)
We are grateful to the Medical Research Council for funding the research through a studentship to Barbara Musial and an in vivo skills award (MR/J500458/1 and MRC CORD G0600717).