Placental restriction reduces insulin sensitivity and expression of insulin signaling and glucose transporter genes in skeletal muscle, but not liver, in young sheep

De Blasio, Miles J., Gatford, Kathryn L., Harland, M. Lyn, Robinson, Jeffrey S. and Owens, Julie A. 2012, Placental restriction reduces insulin sensitivity and expression of insulin signaling and glucose transporter genes in skeletal muscle, but not liver, in young sheep, Endocrinology, vol. 153, no. 5, pp. 2142-2151, doi: 10.1210/en.2011-1955.

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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(s) De Blasio, Miles J.
Gatford, Kathryn L.
Harland, M. Lyn
Robinson, Jeffrey S.
Owens, Julie A.ORCID iD for Owens, Julie A. orcid.org/0000-0002-7498-1353
Journal name Endocrinology
Volume number 153
Issue number 5
Start page 2142
End page 2151
Total pages 10
Publisher Oxford University Press
Place of publication Oxford, Eng.
Publication date 2012-05
ISSN 1945-7170
Keyword(s) Animals
Blood Glucose
Female
Fetal Growth Retardation
Glucose Transport Proteins, Facilitative
Insulin
Liver
Muscle, Skeletal
Placenta
Placental Insufficiency
Pregnancy
Sheep
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
LOW-BIRTH-WEIGHT
INTRAUTERINE GROWTH RESTRICTION
DEPENDENT DIABETES-MELLITUS
ACTIVATED PROTEIN-KINASE
FOR-GESTATIONAL-AGE
GLYCOGEN-SYNTHESIS
METABOLIC SYNDROME
ACTIVITY CONTRIBUTE
POSTNATAL-GROWTH
FEEDING-ACTIVITY
Summary 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 and liver of young lambs. Whole-body insulin sensitivity was measured at 30 d by 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%), GSK3α (-35%), and GYS1 (-31%) overall (each P < 0.05) and decreased AMPKγ3 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, AMPKγ2, and AMPKγ3 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.
Language eng
DOI 10.1210/en.2011-1955
Field of Research 07 Agricultural And Veterinary Sciences
11 Medical And Health Sciences
06 Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2012, The Endocrine Society
Persistent URL http://hdl.handle.net/10536/DRO/DU:30116802

Document type: Journal Article
Collection: Office of the Deputy Vice-Chancellor (Research)
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