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Am J Physiol Endocrinol Metab 296: E272-E281, 2009. First published November 11, 2008; doi:10.1152/ajpendo.90473.2008
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Early exercise regimen improves insulin sensitivity in the intrauterine growth-restricted adult female rat offspring

Meena Garg,1,* Manikkavasagar Thamotharan,1,* Shilpa A. Oak,1 Gerald Pan,1 Duncan C. MacLaren,1 Paul W. N. Lee,2 and Sherin U. Devaskar1

1Division of Neonatology and Developmental Biology, Neonatal Research Center, Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles; and 2Harbor-UCLA Medical Center, Torrance, California

Submitted 28 May 2008 ; accepted in final form 6 November 2008

We examined the effect of early exercise training (Ex) on glucose kinetics, basal, and insulin-stimulated skeletal muscle (SKM) plasma membrane (PM) GLUT4 in pre- and/or postnatal nutrient-restricted adult rat offspring compared with sedentary (Sed) state. Pregestational control female (Ex CON vs. Sed CON) and offspring exposed to prenatal (Ex IUGR vs. Sed IUGR), postnatal (Ex PNGR vs. Sed PNGR), or pre- and postnatal (Ex IUGR + PNGR vs. Sed IUGR + PNGR) nutrient restriction were studied. The combined effect of exercise and pre/postnatal nutrition in the Ex IUGR demonstrated positive effects on basal and glucose-stimulated plasma insulin response (GSIR) with suppression of endogenous hepatic glucose production (HGP) compared with sedentary state. Ex PNGR was hyperglycemic after glucose challenge with no change in glucose-stimulated insulin production or HGP compared with sedentary state. Ex IUGR + PNGR remained glucose tolerant with unchanged glucose-stimulated insulin production but increased endogenous HGP compared with sedentary state. Basal SKM PM-associated GLUT4 was unchanged by exercise in all four groups. Whereas Ex PNGR and Ex IUGR + PNGR insulin responsiveness was similar to that of Ex CON, Ex IUGR remained nonresponsive to insulin. Early introduction of regular Ex in the pregestational female offspring had a positive effect on hepatic adaptation to GSIR and HGP in IUGR and IUGR + PNGR, with no effect in PNGR. Change in insulin responsiveness of SKM GLUT4 translocation was observed in exercised IUGR + PNGR and PNGR but not in exercised IUGR.

glucose tolerance test; metabolic programming; glucose transporter 4; insulin-responsive glucose transporter 4 translocation



Address for reprint requests and other correspondence: S. U. Devaskar, 10833 Le Conte Ave., MDCC B2-375, Los Angeles, CA 90095-1752




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Am. J. Physiol. Endocrinol. Metab.Home page
S. Oak, C. Tran, M.-O. Castillo, S. Thamotharan, M. Thamotharan, and S. U. Devaskar
Peroxisome proliferator-activated receptor-{gamma} agonist improves skeletal muscle insulin signaling in the pregestational intrauterine growth-restricted rat offspring
Am J Physiol Endocrinol Metab, August 1, 2009; 297(2): E514 - E524.
[Abstract] [Full Text] [PDF]




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