Proximity to delivery alters insulin sensitivity and glucose metabolism in pregnant mice
Vaughan, Owen R
American Diabetes Association
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Musial, B., Twinn, D., Vaughan, O. R., Ozanne, S., Voshol, P., Sferruzzi-Perri, A., & Fowden, A. (2016). Proximity to delivery alters insulin sensitivity and glucose metabolism in pregnant mice. Diabetes, 65 851-860. https://doi.org/10.2337/db15-1531
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, day (D) 16, and near term, D19, (term 20.5D). Non-pregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by dual energy X-ray absorptiometry, tissue insulin signalling protein abundance by Western blotting, glucose tolerance and utilisation, and insulin sensitivity using acute insulin administration and hyperinsulinaemic-euglycaemic clamps with 3H-glucose infusion. Whole body insulin resistance occurred in D16 pregnant dams in association with basal hyperinsulinaemia, insulin-resistant endogenous glucose production and downregulation of several proteins in hepatic and skeletal muscle insulin signalling 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 signalling proteins. At D16, insulin resistance at whole body, tissue and molecular levels will favour 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.
insulin sensitivity, insulin resistance, glucose metabolism, pregnancy
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).
Medical Research Council (MC_UU_12012/5/B)
British Heart Foundation (FS/09/029/27902)
External DOI: https://doi.org/10.2337/db15-1531
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253160