Faculty Collaboration Database

Increased hepatic peroxisome proliferator-activated receptor-gamma coactivator-1 gene expression in a rat model of intrauterine growth retardation and subsequent insulin resistance. Endocrinology 2002 Jul;143(7):2486-90

Date

06/20/2002

Pubmed ID

12072378

DOI

10.1210/endo.143.7.8898

Scopus ID

2-s2.0-0036283456 (requires institutional sign-in at Scopus site)   82 Citations

Abstract

Uteroplacental insufficiency and subsequent intrauterine growth retardation (IUGR) increase the risk of type 2 diabetes in humans and rats. Unsuppressed endogenous hepatic glucose production is a common component of the insulin resistance associated with type 2 diabetes. Peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) mediates hepatic glucose production by controlling mRNA levels of glucose-6-phosphatase (G-6-Pase), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1,6-bisphosphatase (FBPase). We therefore hypothesized that gene expression of PGC-1 would be increased in juvenile IUGR rat livers, and this increase would directly correlate with hepatic mRNA levels of PEPCK, G-6-Pase, and FBPase, but not glucokinase. We found that IUGR hepatic PGC-1 protein levels were increased to 230 +/- 32% and 310 +/- 47% of control values at d 0 and d 21 of life, respectively. Similarly, IUGR hepatic PGC-1 mRNA levels were significantly elevated at both ages. Concurrent with the increased PGC-1 gene expression, IUGR hepatic mRNA levels of G-6-Pase, PEPCK, and FBPase were also significantly increased, whereas glucokinase mRNA levels were significantly decreased. These data suggest that increased PGC-1 expression and subsequent hepatic glucose production contribute to the insulin resistance observed in the IUGR juvenile rat.

Author List

Lane RH, MacLennan NK, Hsu JL, Janke SM, Pham TD

MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Western
DNA Primers
Female
Fetal Growth Retardation
Gluconeogenesis
Insulin Resistance
Liver
Pregnancy
RNA, Messenger
Rats
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors
Uterus