Post-receptor crosstalk between growth hormone and insulin signal in rats born small for gestational age with catch-up growth

PLoS One. 2014 Jun 25;9(6):e100459. doi: 10.1371/journal.pone.0100459. eCollection 2014.

Abstract

Objective: Insulin resistance has been observed in individuals born small for gestational age (SGA) with catch-up growth (CUG), yet the mechanisms involved remain unclear. This study examined the role of GH and insulin signaling crosstalk in insulin resistance of SGA rats with CUG.

Design and methods: SGA rats were developed by dietary restriction in pregnant rats. GH receptor inhibition was performed on four-week old CUG-SGA and AGA rats. Phosphorylation of IRS-1, AKT, and ERK, and expression of SOCS3 in the skeletal muscle were determined via immunoblot analysis at baseline and after insulin stimulation in CUG-SGA, NCUG-SGA and AGA groups.

Results: Compared to AGA controls, phosphorylation of IRS-1 and AKT in response to insulin stimulation in CUG-SGA rats was significantly blunted (P<0.05), and phosphorylation of ERK at baseline was dramatically activated (P<0.05). SOCS3 expression was significantly increased in CUG-SGA compared to AGA (P = 0.001) and NCUG-SGA (P = 0.006) rats, and was significantly suppressed following GHR inhibition (P<0.05). Furthermore, phosphorylation of IRS-1 and AKT in response to insulin stimulation increased after GHR inhibition (P<0.05).

Conclusions: Insulin resistance in CUG-SGA rats is associated with impairment of IRS-1-PI3K-AKT signaling, which may result from GH signaling-induced up-regulation of SOCS3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Birth Weight*
  • Female
  • Gene Expression Regulation
  • Gestational Age*
  • Insulin Resistance
  • Male
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Cross-Talk*
  • Receptor, Insulin / metabolism*
  • Receptors, Somatotropin / metabolism*
  • Signal Transduction*

Substances

  • Receptors, Somatotropin
  • Receptor, Insulin

Grants and funding

The study was supported by the Natural Science Foundation of China (grant number 81100571) and the Natural Science Foundation of Guangdong Province (grant number S2011020005224). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.