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Positive Correlation between Enhanced Expression of TLR4/MyD88/NF-κB with Insulin Resistance in Placentae of Gestational Diabetes Mellitus.

Feng H, Su R, Song Y, Wang C, Lin L, Ma J, Yang H - PLoS ONE (2016)

Bottom Line: The expression of TLR4 in placentae is positively correlated with local IR (pIRS-1: r = 0.76, p <0.001 and pAkt: r = -0.47, p <0.001) and maternal fasting (r = 0.42, p <0.01), one-hour (r = 0.52, p <0.01) and two-hour glucose (r = 0.54, p <0.01) at OGTT.We found an that enhanced expression of the TLR4-MyD88-NF-kB pathway occurs in GDM placentae, which positively correlates with heightened local IR in placentae and higher maternal hyperglycemia.The TLR4/MyD88/NF-kB pathway may play a potential role in the development of IR in placentae of GDM.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.

ABSTRACT
Insulin resistance (IR) is a critical factor of the pathophysiology of Gestational diabetes mellitus (GDM). Studies on key organs involved in IR, such as livers and adipose tissues, showed that Toll-like receptor 4 (TLR4) can regulate insulin sensitivity. As a maternal-fetal interface with multi-functions, placentae could contribute to the development of IR for GDM. Thus, we investigated the expressions of TLR4/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB) in term placentae from 33 GDM women and 36 healthy pregnant women with normal glucose tolerance, evaluated local and systemic IR and furthermore identified the association between placental TLR4 and IR. TLR4 protein was expressed in various cells of term placenta, particularly in syncytiotrophoblast of villi. Compared with normal pregnancy, the expression of TLR4/MyD88/NF-kB pathway increased in the placenta of GDM (p<0.05), and these differences were more pronounced in the maternal section of the placenta and the syncytiotrophoblast of villi. In addition, more severe IR was observed in the placenta of GDM patients than the control group, evidenced with higher pIRS-1(ser312) (p<0.001) and lower IRS-1 (p<0.05) as well as pAkt proteins (p<0.01). The expression of TLR4 in placentae is positively correlated with local IR (pIRS-1: r = 0.76, p <0.001 and pAkt: r = -0.47, p <0.001) and maternal fasting (r = 0.42, p <0.01), one-hour (r = 0.52, p <0.01) and two-hour glucose (r = 0.54, p <0.01) at OGTT. We found an that enhanced expression of the TLR4-MyD88-NF-kB pathway occurs in GDM placentae, which positively correlates with heightened local IR in placentae and higher maternal hyperglycemia. The TLR4/MyD88/NF-kB pathway may play a potential role in the development of IR in placentae of GDM.

No MeSH data available.


Related in: MedlinePlus

Insulin signaling pathway in placentae of GDM.Western blotting for the phosphorylation of IRS-1 (Ser312) and phosphorylation of Akt in maternal surface of placentae. Representative western blot images are shown. Compared with normal pregnancy (n = 36), the GDM placentae (n = 33) showed increased IRS-1 phosphorylation (Ser312), decreased IRS-1 and Akt phosphorylation.
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pone.0157185.g005: Insulin signaling pathway in placentae of GDM.Western blotting for the phosphorylation of IRS-1 (Ser312) and phosphorylation of Akt in maternal surface of placentae. Representative western blot images are shown. Compared with normal pregnancy (n = 36), the GDM placentae (n = 33) showed increased IRS-1 phosphorylation (Ser312), decreased IRS-1 and Akt phosphorylation.

Mentions: Using western blot analysis, we further quantified the changes of insulin sensitivity for the GDM placentae. Compared with normal pregnancy, the GDM placentae showed increased IRS-1 phosphorylation (Ser312), decreased IRS-1 and Akt phosphorylation (Fig 5). Furthermore, increased pIRS-1/IRS-1 ratio and decreased pAkt/Akt ratio were observed in the GDM placentae. The changes of IRS-1 and Akt phosphorylation suggested a worse local IR in the GDM placentae.


Positive Correlation between Enhanced Expression of TLR4/MyD88/NF-κB with Insulin Resistance in Placentae of Gestational Diabetes Mellitus.

Feng H, Su R, Song Y, Wang C, Lin L, Ma J, Yang H - PLoS ONE (2016)

Insulin signaling pathway in placentae of GDM.Western blotting for the phosphorylation of IRS-1 (Ser312) and phosphorylation of Akt in maternal surface of placentae. Representative western blot images are shown. Compared with normal pregnancy (n = 36), the GDM placentae (n = 33) showed increased IRS-1 phosphorylation (Ser312), decreased IRS-1 and Akt phosphorylation.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4920413&req=5

pone.0157185.g005: Insulin signaling pathway in placentae of GDM.Western blotting for the phosphorylation of IRS-1 (Ser312) and phosphorylation of Akt in maternal surface of placentae. Representative western blot images are shown. Compared with normal pregnancy (n = 36), the GDM placentae (n = 33) showed increased IRS-1 phosphorylation (Ser312), decreased IRS-1 and Akt phosphorylation.
Mentions: Using western blot analysis, we further quantified the changes of insulin sensitivity for the GDM placentae. Compared with normal pregnancy, the GDM placentae showed increased IRS-1 phosphorylation (Ser312), decreased IRS-1 and Akt phosphorylation (Fig 5). Furthermore, increased pIRS-1/IRS-1 ratio and decreased pAkt/Akt ratio were observed in the GDM placentae. The changes of IRS-1 and Akt phosphorylation suggested a worse local IR in the GDM placentae.

Bottom Line: The expression of TLR4 in placentae is positively correlated with local IR (pIRS-1: r = 0.76, p <0.001 and pAkt: r = -0.47, p <0.001) and maternal fasting (r = 0.42, p <0.01), one-hour (r = 0.52, p <0.01) and two-hour glucose (r = 0.54, p <0.01) at OGTT.We found an that enhanced expression of the TLR4-MyD88-NF-kB pathway occurs in GDM placentae, which positively correlates with heightened local IR in placentae and higher maternal hyperglycemia.The TLR4/MyD88/NF-kB pathway may play a potential role in the development of IR in placentae of GDM.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.

ABSTRACT
Insulin resistance (IR) is a critical factor of the pathophysiology of Gestational diabetes mellitus (GDM). Studies on key organs involved in IR, such as livers and adipose tissues, showed that Toll-like receptor 4 (TLR4) can regulate insulin sensitivity. As a maternal-fetal interface with multi-functions, placentae could contribute to the development of IR for GDM. Thus, we investigated the expressions of TLR4/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB) in term placentae from 33 GDM women and 36 healthy pregnant women with normal glucose tolerance, evaluated local and systemic IR and furthermore identified the association between placental TLR4 and IR. TLR4 protein was expressed in various cells of term placenta, particularly in syncytiotrophoblast of villi. Compared with normal pregnancy, the expression of TLR4/MyD88/NF-kB pathway increased in the placenta of GDM (p<0.05), and these differences were more pronounced in the maternal section of the placenta and the syncytiotrophoblast of villi. In addition, more severe IR was observed in the placenta of GDM patients than the control group, evidenced with higher pIRS-1(ser312) (p<0.001) and lower IRS-1 (p<0.05) as well as pAkt proteins (p<0.01). The expression of TLR4 in placentae is positively correlated with local IR (pIRS-1: r = 0.76, p <0.001 and pAkt: r = -0.47, p <0.001) and maternal fasting (r = 0.42, p <0.01), one-hour (r = 0.52, p <0.01) and two-hour glucose (r = 0.54, p <0.01) at OGTT. We found an that enhanced expression of the TLR4-MyD88-NF-kB pathway occurs in GDM placentae, which positively correlates with heightened local IR in placentae and higher maternal hyperglycemia. The TLR4/MyD88/NF-kB pathway may play a potential role in the development of IR in placentae of GDM.

No MeSH data available.


Related in: MedlinePlus