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Type: Journal article
Title: Placental restriction reduces insulin sensitivity and expression of insulin signaling and glucose transporter genes in skeletal muscle, but not liver, in young sheep
Author: De Blasio, M.
Gatford, K.
Harland, M.
Robinson, J.
Owens, J.
Citation: Endocrinology, 2012; 153(5):2142-2151
Publisher: Endocrine Soc
Issue Date: 2012
ISSN: 0013-7227
Statement of
Miles J. De Blasio, Kathryn L. Gatford, M. Lyn Harland, Jeffrey S. Robinson and Julie A. Owens
Abstract: Poor growth before birth is associated with impaired insulin sensitivity later in life, increasing the risk of type 2 diabetes. The tissue sites at which insulin resistance first develops after intrauterine growth restriction (IUGR), and its molecular basis, are unclear. We have therefore characterized the effects of placental restriction (PR), a major cause of IUGR, on whole-body insulin sensitivity and expression of molecular determinants of insulin signaling and glucose uptake in skeletal muscle andliver ofyounglambs. Whole-body insulin sensitivitywasmeasured at 30dby hyperinsulinaemic euglycaemic clamp and expression of insulin signaling genes (receptors, pathways, and targets) at 43 d in muscle and liver of control (n = 15) and PR (n = 13) lambs. PR reduced size at birth and increased postnatal growth, fasting plasma glucose (+15%, P < 0.004), and insulin (+115%, P = 0.009). PR reduced whole-body insulin sensitivity (-43%, P_0.001) and skeletal muscle expression of INSR (- 36%), IRS1 (-28%), AKT2 (- 44%), GLUT4 (- 88%), GSK3 (-35%), and GYS1 (-31%) overall (each P < 0.05) and decreased AMPK3 expression in females (P = 0.030). PR did not alter hepatic expression of insulin signaling and related genes but increased GLUT2 expression (P = 0.047) in males. Whole-body insulin sensitivity correlated positively with skeletal muscle expression of IRS1,AKT2,HK,AMPK2, andAMPK3 in PR lambs only (each P<0.05) but not with hepatic gene expression in control or PR lambs. Onset of insulin resistance after PR and IUGR is accompanied by, and can be accounted for by, reduced expression of insulin signaling and metabolic genes in skeletal muscle but not liver.
Keywords: Muscle, Skeletal; Liver; Placenta; Animals; Sheep; Fetal Growth Retardation; Placental Insufficiency; Insulin; Blood Glucose; Pregnancy; Female; Glucose Transport Proteins, Facilitative
Rights: © 2012 by The Endocrine Society
RMID: 0020119134
DOI: 10.1210/en.2011-1955
Appears in Collections:Obstetrics and Gynaecology publications

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