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Interleukin-1? inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

ABSTRACT: Interleukin-1? (IL-1?) promotes insulin resistance in tissues such as liver and skeletal muscle; however the influence of IL-1? on placental insulin signaling is unknown. We recently reported increased IL-1? protein expression in placentas of obese mothers, which could contribute to insulin resistance. In this study, we tested the hypothesis that IL-1? inhibits insulin signaling and prevents insulin-stimulated amino acid transport in cultured primary human trophoblast (PHT) cells. Cultured trophoblasts isolated from term placentas were treated with physiological concentrations of IL-1? (10pg/ml) for 24h. IL-1? increased the phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser307 (inhibitory) and decreased total IRS-1 protein abundance but did not affect insulin receptor ? expression. Furthermore, IL-1? inhibited insulin-stimulated phosphorylation of IRS-1 (Tyr612, activation site) and Akt (Thr308) and prevented insulin-stimulated increase in PI3K/p85 and Grb2 protein expression. IL-1? alone stimulated cRaf (Ser338), MEK (Ser221) and Erk1/2 (Thr202/Tyr204) phosphorylation. The inflammatory pathways nuclear factor kappa B and c-Jun N-terminal kinase, which are involved in insulin resistance, were also activated by IL-1? treatment. Moreover, IL-1? inhibited insulin-stimulated System A, but not System L amino acid uptake, indicating functional impairment of insulin signaling. In conclusion, IL-1? inhibited the insulin signaling pathway by inhibiting IRS-1 signaling and prevented insulin-stimulated System A transport, thereby promoting insulin resistance in cultured PHT cells. These findings indicate that conditions which lead to increased systemic maternal or placental IL-1? levels may attenuate the effects of maternal insulin on placental function and consequently fetal growth.

SUBMITTER: Aye IL

PROVIDER: S-EPMC3795822 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

Aye Irving L M H IL Jansson Thomas T Powell Theresa L TL

Molecular and cellular endocrinology 20130725 1-2

Interleukin-1β (IL-1β) promotes insulin resistance in tissues such as liver and skeletal muscle; however the influence of IL-1β on placental insulin signaling is unknown. We recently reported increased IL-1β protein expression in placentas of obese mothers, which could contribute to insulin resistance. In this study, we tested the hypothesis that IL-1β inhibits insulin signaling and prevents insulin-stimulated amino acid transport in cultured primary human trophoblast (PHT) cells. Cultured troph ...[more]

PMID: 23891856

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Dataset Information

Interleukin-1? inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

Publications

Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

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