Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/72793
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
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 1945-7170 |
Statement of Responsibility: | 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 AMPK3 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,AMPK2, andAMPK3 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 |
DOI: | 10.1210/en.2011-1955 |
Published version: | http://dx.doi.org/10.1210/en.2011-1955 |
Appears in Collections: | Aurora harvest 5 Obstetrics and Gynaecology publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.