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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070916 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0100459 | PLOS |
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