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Article Dans Une Revue Journal of Biological Chemistry Année : 2016

Discrepancy in insulin regulation between GDM-platelets and -placenta

Résumé

Earlier findings have identified the requirement of the insulin signaling on maturation and the translocation of serotonin (5-HT) transporter, SERT to the plasma membrane of the trophoblast in placenta. Due to the defect on insulin receptor (IR) in the trophoblast of the gestational diabetes mellitus (GDM)-associated placenta, SERT is found entrapped in the cytoplasm of the GDM-trophoblast. SERT is encoded by the same gene expressed in trophoblast and platelets. Additionally, alteration in plasma 5-HT levels and the 5-HT uptake rates are associated with the aggregation rates of platelets. Therefore, here, we investigated a novel hypothesis that GDM-associated defect in platelet IR should change their 5-HT uptake rates and this should be a leading factor for thrombosis in GDM maternal blood. The maternal blood and the placentas were obtained at the time of cesarean section from the GDM and non-diabetic subjects (n = 6 for each group) and the platelets and trophoblasts were isolated to determine the IR activity, surface level of SERT and their 5-HT uptake rates. Interestingly, no significant differences were evident in IR tyrosine phosphorylation or the downstream elements, AKT and S6K in platelets and their aggregation rates in both groups. Furthermore, insulin stimulation upregulated 5-HT uptake rates of GDM-platelets as it does in control group. However, the phosphorylation of IR and the downstream elements were significantly lower in GDM-trophoblast and showed no response to the insulin stimulation while they showed 4-fold increase to insulin stimulation in control group. Similarly, the 5-HT uptake rates of GDM-trophoblast and the SERT expression on their surface were several fold lower compared with control subjects. IR is expressed in all tissues, but it is not known if diabetes effects IR in all tissues equally. Here, for the first time, our findings with clinical samples show that in GDM-associated defect on IR is tissue-type dependent. While IR is impaired in GDM-placenta, it is unaffected in GDM-platelet.
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Dates et versions

hal-01280557 , version 1 (02-03-2016)

Identifiants

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Yicong Li, Anthonya Cooper, Imelda N Odibo, Asli Ahmed, Pamela Murphy, et al.. Discrepancy in insulin regulation between GDM-platelets and -placenta. Journal of Biological Chemistry, 2016, ⟨10.1074/jbc.M116.713693⟩. ⟨hal-01280557⟩
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